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The treatment of hepatitis is individual specific. If you are looking for specifics on whether a Naturopathic Doctor can
treat your cross infection between Hepatitis B with your odd Hepatitis E antigen markers, the answer is probably.
It may be possible to treat oneself entirely without another doctor's help. It is said of doctors who treat themselves
that they have fools for patients. So it may be wise to consider whether you would undertake an engine overhaul if you were
not a mechanic. If not, it might be best to at least ask a mechanic what they would do.
The following are simply medline research reports on Hepatitis B and C for your information. They are not a replacement
for medical care.
If you would like a summary of the research, please check out my articles at www.hepatitismagazine.com. (My home page
has a direct link available).
Drugs. 2001;61(14):2035-63. Related Articles, Links
The use of silymarin in the treatment of liver diseases.
Saller R, Meier R, Brignoli R.
Abteilung Naturheilkunde, University Hospital Zurich, Switzerland.
The high prevalence of liver diseases such as chronic hepatitis and cirrhosis underscores the need for efficient and cost-effective
treatments. The potential benefit of silymarin (extracted from the seeds of Silybum marianum or milk thistle) in the treatment
of liver diseases remains a controversial issue. Therefore, the objective of this review is to assess the clinical efficacy
and safety of silymarin by application of systematic approach. 525 references were found in the databases, of which 84 papers
were retained for closer examination and 36 were deemed suitable for detailed analysis. Silymarin has metabolic and cell-regulating
effects at concentrations found in clinical conditions, namely carrier-mediated regulation of cell membrane permeability,
inhibition of the 5-lipoxygenase pathway, scavenging of reactive oxygen species (ROS) of the R-OH type and action on DNA-expression,
for example, via suppression of nuclear factor (NF)-kappaB. Pooled data from case record studies involving 452 patients with
Amanita phalloides poisoning show a highly significant difference in mortality in favour of silibinin [the main isomer contained
in silymarin] (mortality 9.8% vs 18.3% with standard treatment; p < 0.01). The available trials in patients with toxic
(e.g. solvents) or iatrogenic (e.g. antispychotic or tacrine) liver diseases, which are mostly outdated and underpowered,
do not enable any valid conclusions to be drawn on the value of silymarin. The exception is an improved clinical tolerance
of tacrine. In spite of some positive results in patients with acute viral hepatitis, no formally valid conclusion can be
drawn regarding the value of silymarin in the treatment of these infections. Although there were no clinical end-points in
the four trials considered in patients with alcoholic liver disease, histological findings were reported as improved in two
out of two trials, improvement of prothrombin time was significant (two trials pooled) and liver transaminase levels were
consistently lower in the silymarin-treated groups. Therefore, silymarin may be of use as an adjuvant in the therapy of alcoholic
liver disease. Analysis was performed on five trials with a total of 602 patients with liver cirrhosis. The evidence shows
that, compared with placebo, silymarin produces a nonsignificant reduction of total mortality by -4.2% [odds ratio (OR) 0.75
(0.5 - 1.1)]; but that, on the other hand, the use of silymarin leads to a significant reduction in liver-related mortality
of-7% [OR: 0.54 (0.3 - 0.9); p < 0.01]. An individual trial reported a reduction in the number of patients with encephalopathy
of -8.7% (p = 0.06). In one study of patients with cirrhosis-related diabetes mellitus, the insulin requirement was reduced
by -25% (p < 0.01). We conclude that available evidence suggests that silymarin may play a role in the therapy of (alcoholic)
liver cirrhosis. Silymarin is has a good safety record and only rare case reports of gastrointestinal disturbances and allergic
skin rashes have been published. This review does not aim to replace future prospective trials aiming to provide the 'final'
evidence of the efficacy of silymarin.
Publication Types:
Review
Review, Tutorial
PMID: 11735632 [PubMed - indexed for MEDLINE]
J Toxicol Clin Toxicol. 2002;40(6):715-57. Related Articles, Links
Treatment of amatoxin poisoning: 20-year retrospective analysis.
Enjalbert F, Rapior S, Nouguier-Soule J, Guillon S, Amouroux N, Cabot C.
Laboratoire de Botanique, Phytochimie et Mycologie, Faculte de Pharmacie, Universite Montpellier 1, France. fenjalbert@ww3.pharma.univ-montp1.fr
BACKGROUND: Amatoxin poisoning is a medical emergency characterized by a long incubation time lag, gastrointestinal and
hepatotoxic phases, coma, and death. This mushroom intoxication is ascribed to 35 amatoxin-containing species belonging to
three genera: Amanita, Galerina, and Lepiota. The major amatoxins, the alpha-, beta-, and gamma-amanitins, are bicyclic octapeptide
derivatives that damage the liver and kidney via irreversible binding to RNA polymerase II. METHODS: The mycology and clinical
syndrome of amatoxin poisoning are reviewed. Clinical data from 2108 hospitalized amatoxin poisoning exposures as reported
in the medical literature from North America and Europe over the last 20 years were compiled. Preliminary medical care, supportive
measures, specific treatments used singly or in combination, and liver transplantation were characterized. Specific treatments
consisted of detoxication procedures (e.g., toxin removal from bile and urine, and extracorporeal purification) and administration
of drugs. Chemotherapy included benzylpenicillin or other beta-lactam antibiotics, silymarin complex, thioctic acid, antioxidant
drugs, hormones and steroids administered singly, or more usually, in combination. Supportive measures alone and 10 specific
treatment regimens were analyzed relative to mortality. RESULTS: Benzylpenicillin (Penicillin G) alone and in association
was the mostfrequently utilized chemotherapy but showed little efficacy. No benefit was found for the use of thioctic acid
or steroids. Chi-square statistical comparison of survivors and dead vs. treated individuals supported silybin, administered
either as mono-chemotherapy or in drug combination and N-acetylcysteine as mono-chemotherapy as the most effective therapeutic
modes. Future clinical research should focus on confirming the efficacy of silybin, N-acetylcysteine, and detoxication procedures.
Publication Types:
Review
PMID: 12475187 [PubMed - indexed for MEDLINE]
J Pharm Belg. 2003;58(1):28-31. Related Articles, Links
[St. Mary's Thistle: an overview]
[Article in French]
Laekeman G, De Coster S, De Meyer K.
K.U.Leuven.
St. Marys Thistle has been approved for registration as a regular medicine in Belgium. The hepatotropic properties of
this plant are rather difficult to evaluate objectively. Mortality rate in case of life-threatening hepatic diseases is the
most objective parameter. Legalon is the only drug registered in Belgium. It has a prescription only status. The plant Silybum
marianum is a thistle and as a consequence belongs to the Compositae. There is a limited production of St.-Marys Thistle in
Pajottenland, west of Brussels. The seeds are exported to Italy in order to extract silymarine, a mixture of flavonolignanes
with antioxidant properties. Silymarine has been tested in living animals deliberately intoxicated with mushroom toxins, medicines,
heavy metals or toxic organic solvents. Preventive as well as curative activity has been confirmed. Silymarine accumulates
in the liver, which is also the target organ in therapy. Silymarine improves the prognosis after accidental ingestion of the
toxic Amanita phalloides. Patients infected with hepatitis B and C might benefit from Silymarine, but more data have to be
generated. Silymarine given to patients with liver damages by alcohol lowers the death toll. The drug has a general safety
pattern comparable to placebo.
Publication Types:
Review
Review, Tutorial
PMID: 12722542 [PubMed - indexed for MEDLINE]
Indian J Physiol Pharmacol. 2002 Apr;46(2):167-74. Related Articles, Links
Evaluation of hepatoprotective activity of Ginkgo biloba in rats.
Shenoy KA, Somayaji SN, Bairy KL.
Department of Pharmacology, Kasturba Medical College, Mangalore-575 001.
The mechanism of hepatoprotective effects of Ginkgo biloba (GB), an herbal preparation with wide variety of therapeutic
application, on paracetamol (Pcml) induced hepatic damage in rats has been investigated. GB treatment restored the marker
enzyme levels indicating the in vivo protective effects against Pcml induced liver damage both in preventive and curative
aspects. GB also reversed the increased TBARS levels, and elevated the GSH content of the liver. The results obtained from
the study indicate hepatoprotective nature of GB, which might be due to its ability to prevent lipid peroxidation and replenishing
the gllutathione level. The effects of GB were comparable to that of silymarin.
PMID: 12500491 [PubMed - indexed for MEDLINE]
J Med Food. 2002 Fall;5(3):171-7. Related Articles, Links
Hepatoprotective activity of Moringa oleifera on antitubercular drug-induced liver damage in rats.
Pari L, Kumar NA.
Department of Biochemistry, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu - 608 002, India. paribala@sancharnet.in
Moringa oleifera Lam (Moringaceae), commonly known as "Drumstick," is used in Indian folk medicine for the treatment
of various illness. We have evaluated the hepatoprotective effect of an ethanolic extract of M. oleifera leaves on liver damage
induced by antitubercular drugs such as isoniazid (INH), rifampicin (RMP), and pyrazinamide (PZA) in rats. Oral administration
of the extract showed a significant protective action made evident by its effect on the levels of glutamic oxaloacetic transaminase
(aspartate aminotransferase), glutamic pyruvic transaminase (alanine aminotransferase), alkaline phosphatase, and bilirubin
in the serum; lipids, and lipid peroxidation levels in liver. This observation was supplemented by histopathological examination
of liver sections. The results of this study showed that treatment with M. oleifera extracts or silymarin (as a reference)
appears to enhance the recovery from hepatic damage induced by antitubercular drugs.
PMID: 12495589 [PubMed - indexed for MEDLINE]
J Clin Gastroenterol. 2003 Oct;37(4):336-9. Related Articles, Links
Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons.
Lieber CS, Leo MA, Cao Q, Ren C, DeCarli LM.
Section of Liver Disease & Nutrition, Bronx VA Medical Center & Mount Sinai School of Medicine, Bronx, New York
10468, USA. liebercs@aol.com
GOAL/BACKGROUND: Hepatoprotective effects of silymarin in patients with alcoholic liver disease are controversial. For
strict control, this was assessed in non-human primates.STUDY Twelve baboons were fed alcohol with or without silymarin for
3 years with a nutritionally adequate diet. RESULTS: Silymarin opposed the alcohol-induced oxidative stress (assessed by plasma
4-hydroxynonenal) and the rise in liver lipids and circulating ALT. Alcohol also increased hepatic collagen type I by 50%
over the 3 years with a significant rise in mRNA for alpha1 (I) procollagen, both prevented by silymarin. There were corresponding
morphologic changes: at 36 months, 2 of 6 animals fed alcohol had cirrhosis and 2 septal fibrosis, with perivenular fibrosis
in 2, whereas with alcohol + silymarin, there was only 1 cirrhosis and 1 septal fibrosis, with perivenular fibrosis in 2,
and virtually no lesions in the remaining 2. CONCLUSIONS: Silymarin retards the development of alcohol-induced hepatic fibrosis
in baboons, consistent with several positive clinical trials. The negative outcome observed in other trials possibly reflects
poor compliance resulting in irregular or low silymarin intake. Thus, in view of the innocuity of silymarin, it might be advisable
in future clinical studies to insure the controlled administration of sufficient amounts of silymarin.
PMID: 14506392 [PubMed - indexed for MEDLINE]
Dig Liver Dis. 2004 Nov;36(11):752-9. Related Articles, Links
Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description
and 12-month results.
Tanamly MD, Tadros F, Labeeb S, Makld H, Shehata M, Mikhail N, Abdel-Hamid M, Shehata M, Abu-Baki L, Medhat A, Magder
LS, Afdhal NH, Strickland GT.
International Health Division, Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine,
660 West Redwood St. Suite 100, Baltimore, MD 21201, USA.
BACKGROUND/AIMS: A double-blinded trial evaluating silymarin, an herbal supplement for liver disease, to prevent complications
of chronic hepatitis C virus infection has not been done. SUBJECTS: One hundred and seventy-seven consenting residents of
an Egyptian village with chronic hepatitis C virus were randomly assigned to receive either silymarin or multivitamin supplements.
METHODS: Participants had baseline and follow-up clinical, ultrasound, blood tests and quality-of-life assessments. Community
nurses visited weekly to ascertain compliance, distribute supplements and record adverse effects. RESULTS: At 12 months almost
all of 141 remaining subjects reported feeling better, although symptoms and quality-of-life scores did not differ between
the silymarin and multivitamin groups. Both the silymarin and vitamins were tolerated equally well; and >95% of supplements
were taken by >95% of subjects. One in each group had no detectable hepatitis C virus antibodies while two in the silymarin
group and three receiving multivitamins had undetectable hepatitis C virus RNA. Serum alanine aminotransferase elevations
did not differ between groups. Serum hepatic fibrosis marker, hyaluronic acid and YKL-40, and abdominal ultrasound results
were similar in both groups and may have progressed slightly at 12 months. CONCLUSIONS: The recommended dose of silymarin
can be safely taken for 1 year and improves symptoms and general well-being, but has no effect upon hepatitis C virus viremia,
serum ALT, or serum and ultrasound markers for hepatic fibrosis. More prolonged evaluation and a higher dose may be required
to ascertain whether milk thistle supplements prevent complications of chronic hepatitis C virus.
PMID: 15571006 [PubMed - in process]
Toxicology. 2005 Jan 5;206(1):1-15. Related Articles, Links
Amelioration of lead toxicity on rat liver with Vitamin C and silymarin supplements.
Shalan MG, Mostafa MS, Hassouna MM, El-Nabi SE, El-Refaie A.
Biological and Geological Sciences Department, Al-Arish Faculty of Education, Suez Canal University, Center of Town, Al-Arish,
North Sinai 02, Egypt.
The aim of the present study was to investigate the impact of the combined administration of Vitamin C and silymarin on
lead toxicity. Male albino rats were subdivided into three groups: the first was a control group, the second received lead
acetate in diet as 500mg/kg diet daily, the third received the same lead acetate dose and supplemented with Vitamin C (1mg/100g
body weight) and silymarin (1mg/100g body weight) by gastric tube three times per week. Blood samples were taken after 2,
4 and 6 weeks of treatment. Significant lead-induced elevations in serum ALT, AST, GGT and ALP activities were observed after
different periods of treatment. However, serum LDLc was decreased. The intensities of RNA and apoptotic fragments of DNA were
measured as optical density by Gel-pro program. Lead acetate decreased the intensity of DNA at 6 weeks and induced apoptotic
DNA fragments reversibly with time. After 2 weeks of lead administration dilation and congestion of terminal hepatic veins
and portal vein branches were observed. Lead also induced hepatocyte proliferation without any localized distribution among
zones 1-3. Portal inflammatory infiltrate with disruption of the limiting plates (interface hepatitis), steatosis, apoptosis
and mild fibrosis were detected especially by sixth week of lead administration. Combined treatment of lead-exposed animals
with Vitamin C and silymarin showed marked improvement of the biochemical, molecular and histopathological findings. These
experimental results strongly indicate the protective effect of Vitamin C and silymarin against toxic effects of lead on liver
tissue.
PMID: 15590105 [PubMed - in process]
J Dairy Sci. 2004 Jul;87(7):2239-47. Related Articles, Links
Effects of silymarin, a natural hepatoprotector, in periparturient dairy cows.
Tedesco D, Tava A, Galletti S, Tameni M, Varisco G, Costa A, Steidler S.
Department of Veterinary Science and Technology for Food Safety, Faculty of Veterinary Medicine, University of Milan,
Via Celoria 10, 20133, Milan, Italy. doriana.tedesco@unimi.it
Silymarin, a natural acknowledged hepatoprotector used in humans to treat liver diseases, has been tested in dairy cows
during peripartum, a period during which animals are subject to subclinical fatty liver. Ten grams of silymarin (76% pure
extract consisting in flavonolignans, taxifolin, and other trace compounds) per day, was administered as a water suspension
by an oral drench to 15 cows from d 10 before expected calving to 15 d after calving. Milk production was measured, and colostrum,
milk, and blood samples were analyzed during the experimental period. Treated animals showed the peak of milk production at
55 +/- 1.85 d after calving, 1 wk before the control group (62 +/- 3.27 d); the average peak production was 41.6 +/- 1.05
kg for the treated group vs. 39.1 +/- 1.44 kg for the control; the treated animals maintained a greater milk production than
control cows throughout lactation (9922.1 +/- 215.7 vs. 9597.8 +/- 225.4 kg). Milk composition was unaffected by treatment.
No silymarin residues were detected in colostrum and all milk samples. After calving, body condition score (BCS) decrease
was greater for control compared with treated cows. Glucose, urea, triglycerides (TG), total cholesterol, beta-hydroxibutyrate
(BHBA), and gamma-glutamyl transferase (GGT) in plasma were unaffected by treatment. Plasma nonesterified fatty acids (NEFA)
on d-7 were higher in treated cows compared with the control group (741 vs. 181 micromol/L). From this evidence, it is possible
to conclude that silymarin beneficially affected lactation performances and body condition of treated animals. Blood and milk
parameters do not indicate any adverse effects of feeding this natural compound.
PMID: 15328238 [PubMed - indexed for MEDLINE]
Phytother Res. 2002 Nov;16(7):632-8. Related Articles, Links
Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities.
Zuber R, Modriansky M, Dvorak Z, Rohovsky P, Ulrichova J, Simanek V, Anzenbacher P.
Faculty of Chemical Technology, University of Pardubice, Nam. Cs. Legii 565, 532 10 Pardubice, Czech Republic.
Silybin and related flavonolignans form a major part of the Silybum marianum extract, silymarin, which has been used to
treat liver diseases for hundreds of years. Although regarded as safe, many of the extract constituents remain thus far untested
for their possible effects on liver biotransformation enzymes. Cytochromes P450 (CYP) are very important in this regard. We
tested the effect of four flavonolignans: silybin, its hemisynthetic derivative dehydrosilybin, silydianin, and silycristin
on three specific CYP activities: bufuralol 1'-hydroxylation (CYP2D6), p-nitrophenol hydroxylation (CYP2E1), and nifedipine
oxidation (CYP3A4). All flavonolignans displayed dose-dependent inhibition of these activities with IC(50) values in the micromolar
range. The inhibition was competitive or mixed as revealed by double reciprocal plots of kinetic experiments. However, the
inhibition is not considered to be relevant for therapy because physiological concentrations of the individual flavonolignans
do not exceed 0.5 microM. The data support the use of the extract as a dietary supplement. Copyright 2002 John Wiley &
Sons, Ltd.
PMID: 12410543 [PubMed - indexed for MEDLINE]
J Ethnopharmacol. 2004 May;92(1):67-70. Related Articles, Links
Further studies on the antihepatotoxic activity of Phyllanthus maderaspatensis Linn.
Asha VV, Akhila S, Wills PJ, Subramoniam A.
Molecular Ethnopharmacology, Rajiv Gandhi Centre for Biotechnology, Kerala, India. ashavv@rediffmail.com
Phyllanthus maderaspatensis (whole plant extracts) was evaluated for its antihepatotoxic and choleretic activities in
rats. The plant extracts (200 mg/kg, n-hexane, ethyl alcohol or water) showed a remarkable hepatoprotective activity against
acetaminophen-induced hepatotoxicity as judged from the serum marker enzymes. The water and ethyl alcohol extracts showed
moderate activity compared to the n-hexane extract, which showed activity at a dose as low as 1.5 mg/kg. The antihepatotoxicity
of the hexane extract was found to be better than silymarin, a standard hepatoprotective herbal drug. The effect of n-hexane
extract was found to be concentration-dependent. This extract also exhibited choleretic activity in normal rats, and in vitro
hydroxyl radical scavenging activity and inhibition of lipid peroxidation. Copyright 2004 Elsevier Ireland Ltd.
PMID: 15099850 [PubMed - indexed for MEDLINE]
Planta Med. 1999 Oct;65(7):673-5. Related Articles, Links
Isolation of ani-hepatotoxic principle form the juice of Ecballium elaterium.
Agil A, Miro M, Jimenez J, Aneiros J, Caracuel MD, Garcia-Granados A, Navarro MC.
The antihepatotoxic activity of elaterium (dried juice of the fruits of Ecballium elaterium, Cucurbitaceae) and cucurbitacin
B (isolated from the juice) was studied against CCl4-induced hepatotoxicity. Pre- and posttreatment with elaterium and cucurbitacin
B reduced CCl4-hepatotoxicity, as shown reduction in the anormally increased sGPT levels. Posttreatment caused a significant
reduction in the degree of steatosis observed inthe control group, treated only with CCl4. In conclusion, elaterium and cucurbitacin
B had preventive and curative effects against CCl4-induced hepatotoxicity.
Publication Types:
Letter
PMID: 15609462 [PubMed - indexed for MEDLINE]
J Ethnopharmacol. 2003 Aug;87(2-3):237-40. Related Articles, Links
Antihepatotoxic activity of seeds of Cichorium intybus.
Ahmed B, Al-Howiriny TA, Siddiqui AB.
Antihepatotoxic Research Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard
Nagar, 110062, New Delhi, India. drbahmed@rediffmail.com
The different fractions of alcoholic extract and one phenolic compound AB-IV of seeds of Cichorium intybus Linn were screened
for antihepatotoxic activity on carbon tetrachloride (CCl(4))-induced liver damage in albino rats. The degree of protection
was measured using biochemical parameters like aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase
(ALKP), and total protein (TP). The methanol fraction and compound AB-IV were found to possess a potent antihepatotoxic activity
comparable to the standard drug Silymarin (Silybon-70). The histopathological study of the liver was also carried out, wherein
the methanolic fraction and compound AB-IV showed almost complete normalization of the tissues as neither fatty accumulation
nor necrosis was observed.
PMID: 12860315 [PubMed - indexed for MEDLINE]
J Ethnopharmacol. 2002 Mar;79(3):313-6. Related Articles, Links
Hepatoprotective activity of two plants belonging to the Apiaceae and the Euphorbiaceae family.
Ahmed B, Alam T, Varshney M, Khan SA.
Department of Pharmaceutical Chemistry, Antihepatotoxic Research Laboratory, Faculty of Pharmacy, Jamia Hamdard, Hamdard
Nagar, New Delhi 110 062, India. baharchem@yahoo.com
The different extracts of Apium graveolens Linn. (Apiaceae) and Croton oblongifolius Roxb. (Euphorbiaceae) were tested
for their hepatoprotective activity against CCl(4) induced hepatotoxicity in albino rats. The degree of protection was measured
by using biochemical parameters like serum transaminases (SGOT and SGPT), alkaline phosphatase, total protein and albumin.
The methanolic extracts showed the most significant hepatoprotective activity comparable with standard drug silymarin. Other
extracts namely petroleum ether and acetone also exhibited a potent activity.
PMID: 11849834 [PubMed - indexed for MEDLINE]
J Ethnopharmacol. 2001 Jul;76(2):187-9. Related Articles, Links
Hepatoprotective activity of Luffa echinata fruits.
Ahmed B, Alam T, Khan SA.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, 110062, New Delhi, India. root@hamduni.ren.nic.in
The different extracts of the fruits of Luffa echinata Roxb. (Cucurbitaceae) were tested for their hepatoprotective activity
against CCl(4) induced hepatotoxicity in albino rats. The degree of protection was measured by using biochemical parameters
like serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALKP),
total protein (TP) and total albumin (TA). The petroleum ether, acetone and methanolic extracts showed a significant hepatoprotective
activity comparable with those of Silymarin.
PMID: 11390135 [PubMed - indexed for MEDLINE]
Int J Food Sci Nutr. 1999 Nov;50(6):413-27. Related Articles, Links
Allied studies on the effect of Rosmarinus officinalis L. on experimental hepatotoxicity and mutagenesis.
Fahim FA, Esmat AY, Fadel HM, Hassan KF.
Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
The hepatoprotective and antimutagenic effects of the rosemary essential oil and the ethanolic extract were investigated
using carbon tetrachloride and cyclophosphamide as hepatotoxic and mutagenic compounds, respectively. Our results revealed
that i.g. administration of the rosemary ethanolic extract (0.15 g/100 g BW) to rats for 3 weeks produced the most pronounced
hepatoprotective effect compared to silymarin (reference compound) due to the amelioration of most of the studied serum and
liver parameters and confirmed by histopathological examination of the liver tissue. Pretreatment of mice for 7 days with
the rosemary essential oil (1.1 mg/g BW) followed by i.p. injection with cyclophosphamide reduced significantly the induced
mitodepression in the bone marrow cells of the animals. The potential hepatoprotective and antimutagenic activities of the
rosemary ethanolic extract and essential oil, respectively, are attributed to the presence of a relatively high percentage
of phenolic compounds with high antioxidant activity (according to our chemical studies).
PMID: 10719582 [PubMed - indexed for MEDLINE]
Cell Death Differ. 2003 Jan;10 Suppl 1:S59-67. Related Articles, Links
Hepatitis C and liver fibrosis.
Schuppan D, Krebs A, Bauer M, Hahn EG.
Department of Medicine I, University of Erlangen-Nuernberg, Germany. detlef.schuppan@med1.imed.uni-erlangen.de
Chronic hepatitis C progresses to cirrhosis within 20 years in an estimated 20-30% of patients, while running a relatively
uneventful course in most others. Certain HCV proteins, such as core and NS5A, can induce derangement of lipid metabolism
or alter signal transduction of infected hepatocytes which leads to the production of reactive oxygen radicals and profibrogenic
mediators, in particular TGF-beta1. TGF-beta1 is the strongest known inducer of fibrogenesis in the effector cells of hepatic
fibrosis, i.e. activated hepatic stellate cells and myofibroblasts. However, fibrogenesis proceeds only when additional profibrogenic
stimuli are present, e.g. alcohol exposure, metabolic disorders such as non-alcoholic steatohepatitis, or coinfections with
HIV or Schistosoma mansoni that skew the immune response towards a Th2 T cell reaction. Furthermore, profibrogenic polymorphisms
in genes that are relevant during fibrogenesis have been disclosed. This knowledge will make it possible to identify those
patients who are most likely to progress and who need antiviral or antifibrotic therapies most urgently. However, even the
best available treatment, the combination of pegylated interferon and ribavirin, which is costly and fraught with side effects,
eradicates HCV in only 50% of patients. While the suggestive antifibrotic effect of interferons (IF-gamma>alpha,beta),
irrespective of viral elimination, has to be proven in randomised prospective studies, additional, well tolerated and cost-effective
antifibrotic therapies have to be developed. The combination of cytokine strategies, e.g. inhibition of the key profibrogenic
mediator TGF-beta, with other potential antifibrotic agents appears promising. Such adjunctive agents could be silymarin,
sho-saiko-to, halofuginone, phosphodiesterase inhibitors, and endothelin-A-receptor or angiotensin antagonists. Furthermore,
drug targeting to the fibrogenic effector cells appears feasible. Together with the evolving validation of serological markers
of hepatic fibrogenesis and fibrolysis an effective and individualised treatment of liver fibrosis is anticipated.
Publication Types:
Review
Review, Tutorial
PMID: 12655347 [PubMed - indexed for MEDLINE]
Leber Magen Darm. 1977 Oct;7(5):318-23. Related Articles, Links
[Results of two double-blind studies on the effect of silymarine in chronic hepatitis (author's transl)]
[Article in German]
Kiesewetter E, Leodolter I, Thaler H.
In two double-blind studies with 24 and 12 patients, respectively, the effect of silymarine on chronic hepatitis was studied.
The treatment lasted three months to one year. In the laboratory tests investigated no remarkable difference between silymarine
and placebo therapy was seen. Some histological changes, however, were improved under silymarine, one of them significantly.
A control of these findings will be necessary. The question arises if silymarine occupies receptors on the liver cell membrane
and therefore causes a partial blocking of immunologic reactions. The difficulties of prospective studies in chronic liver
disease are emphasized.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 926982 [PubMed - indexed for MEDLINE] Med Klin. 1977 Mar 25;72(12):513-8. Related Articles, Links
[Silymarin for the treatment of acute viral hepatitis? Report of a controlled trial (author's transl)]
[Article in German]
Bode JC, Schmidt U, Durr HK.
Silymarin has been claimed to have a benificial effect in various types of liver injury. In a prospective study in patients
with acute viral hepatitis (n = 151) the effectiveness of this drug on the cause of the disease was tested. The groups with
and without Silymarin (Legalon) were comparable concerning age and sex distribution and the frequency of HBs-antigen positive
hepatitis; Laboratory findings (total serum bilirubin, activity of GOT, GPT and alkaline phosphatase and prothrombin time)
were determined in intervals of 5 to 7 days over a period of 5 weeks beginning with the onset of jaundice. There were no statistical
significant differences between both groups in the decrease of mean values of all parameters tested. The frequency of nearly
normalized values of transaminases and serum bilirubin after 10, 20 and 30 days was not higher in the group treated with Silymarin
as compared to the controls. It is concluded that Silymarin has no favourable effects on the cause of acute viral hepatitis.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 840125 [PubMed - indexed for MEDLINE]
BioDrugs. 2001;15(7):465-89. Related Articles, Links
Silymarin: a review of its clinical properties in the management of hepatic disorders.
Wellington K, Jarvis B.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
The mechanisms of action of silymarin involve different biochemical events, such as the stimulation of the synthetic rate
of ribosomal RNA (rRNA) species through stimulation of polymerase I and rRNA transcription, protecting the cell membrane from
radical-induced damage and blockage of the uptake of toxins such as alpha-amanitin. Studies in patients with liver disease
have shown that silymarin increases superoxide dismutase (SOD) activity of lymphocytes and erythrocytes, as well as the expression
of SOD in lymphocytes. Silymarin has also been shown to increase patient serum levels of glutathione and glutathione peroxidase.
Silybin 20 to 48 mg/kg/day has shown promise as a clinical antidote to acute Amanita (deathcap mushroom) poisoning. Primary
efficacy data from 3 trials which examined the therapeutic potential of silymarin in patients with cirrhosis, and included
patient survival as an end-point, demonstrated that silymarin had no significant beneficial effect on patient mortality. However,
upon subanalysis, silymarin 420 mg/day had a significantly beneficial effect on patient survival rate (compared with patients
receiving placebo) in 1 randomised, double-blind trial in patients with alcoholic cirrhosis. Silymarin 420 mg/day was also
shown to improve indices of liver function [AST, ALT, gamma-glutamyl transferase and bilirubin] in patients with liver disease
of various aetiology, including those exposed to toxic levels of toluene or xylene; however, it was largely ineffective in
patients with viral hepatitis. Reports of adverse events while receiving silymarin therapy are rare. However, there have been
accounts of nausea, epigastric discomfort, arthralgia, pruritus, headache and urticaria. Silymarin has also been reported
to have possibly caused a mild laxative effect. CONCLUSION: The antioxidant properties of silymarin (a mixture of at least
4 closely related flavonolignans, 60 to 70% of which is a mixture of 2 diastereomers of silybin) have been demonstrated in
vitro and in animal and human studies. However, studies evaluating relevant health outcomes associated with these properties
are lacking. Although silymarin has low oral absorption, oral dosages of 420 mg/day have shown some therapeutic potential,
with good tolerability, in the treatment of alcoholic cirrhosis. Moreover, silybin 20 to 48 mg/kg/day has shown promise as
an antidote for acute mushroom poisoning by Amanita phalloides; however, further studies paying attention to the amount of
ingested mushroom and time elapsed before administration of treatment are needed to clarify its role in this indication. Studies
in patients with the early onset of liver disease may demonstrate the liver regeneration properties that silymarin is promoted
as possessing.
Publication Types:
Review
Review, Tutorial
PMID: 11520257 [PubMed - indexed for MEDLINE]
Cochrane Database Syst Rev. 2004;(2):CD002904. Related Articles, Links
Glucocorticosteroids for viral hepatitis C.
Brok J, Mellerup MT, Krogsgaard K, Gluud C.
Centre for Clinical Intervention Research, Copenhagen University Hospital, Department 7102, H:S Rigshospitalet, Copenhagen
O, Denmark, DK 2100.
BACKGROUND: Hepatitis C virus may cause liver inflammation and fibrosis. It is not known whether glucocorticosteroids
are beneficial or harmful for patients with hepatitis C infection. OBJECTIVES: The objectives were to evaluate the beneficial
and harmful effects of glucocorticosteroids for patients with acute or chronic hepatitis C infection with or without hepatitis
C related autoimmune disorders. SEARCH STRATEGY: Searches of The Cochrane Hepato-Biliary Controlled Trials Register, The Cochrane
Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and reference lists of relevant articles and hand searches
of relevant journals were performed in July 2003. Principal authors of clinical trials were approached. SELECTION CRITERIA:
Randomised clinical trials dealing with glucocorticosteroids for viral hepatitis C - acute or chronic with or without autoimmune
disorders. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and validated by another. Further information
was sought by correspondence with the principal investigator of the trial in case the relevant data were not published. Disagreements
were solved by discussion before the meta-analysis. MAIN RESULTS: Eight trials randomised 384 patients with chronic hepatitis
C to glucocorticosteroids plus interferon versus interferon plus placebo/no intervention, glucocorticosteroids versus interferon,
or glucocorticosteroids versus placebo. Glucocorticosteroids treatment given as short pre-treatment followed by interferon
or as long-term parallel treatment combined with interferon versus interferon monotherapy had no significant effect on mortality
(no deaths occurred; 342 patients), virological response at six months follow-up (RR 0.85; 95% CI 0.52 to 1.38; 38 patients),
or biochemical response at six months follow-up (RR 0.95; 95% CI 0.84 to 1.06; 307 patients). There was no significant difference
in serious adverse events between combination therapy versus interferon monotherapy (RR 4.76; 95% CI 0.24 to 93.19; 342 patients).
Glucocorticosteroids versus interferon had no significant effect on mortality (RR 2.33; 95% CI 0.27 to 17.80; 13 patients)
or virological response at follow-up (RR 1.17; 95% CI 0.86 to 1.58; 13 patients). We found no trials on glucocorticosteroids
for acute hepatitis C. REVIEWERS' CONCLUSIONS: There is insufficient evidence neither to confirm nor exclude both beneficial
and harmful effects of glucocorticosteroids for chronic hepatitis C with or without autoimmune disorders. This Review is not
able to rule out potential serious adverse effects of glucocorticosteroids. Therefore, this Review cannot establish whether
glucocorticosteroids treatment can be safely administrated for indications requiring glucocorticosteroids without analysing
for hepatitis C virus. The effect of glucocorticosteroids for acute hepatitis C has not been examined in randomised trials.
Publication Types:
Meta-Analysis
Review
PMID: 15106184 [PubMed - indexed for MEDLINE]
Cochrane Database Syst Rev. 2003;(2):CD003181. Related Articles, Links
Bile acids for viral hepatitis.
Chen W, Liu J, Gluud C.
Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, H:S Rigshospitalet, Dept. 7102, Blegdamsvej 9, DK-2100 Copenhagen,
Denmark. w.chen@ctu.rh.dk
BACKGROUND: The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients
with viral hepatitis, but no consensus was reached regarding their usefulness. OBJECTIVES: To assess the beneficial and harmful
effects of bile acids for viral hepatitis. SEARCH STRATEGY: Searches were performed of the trial registers of The Cochrane
Hepato-Biliary Group (September 2002), The Cochrane Library (Issue 2, 2002), MEDLINE (September 2002), EMBASE (September 2002),
and The Chinese Biomedical Database (April 2001). SELECTION CRITERIA: Randomised clinical trials comparing any dose or duration
of bile acids versus placebo or no intervention for viral hepatitis were included, irrespective of language, publication status,
or blinding. DATA COLLECTION AND ANALYSIS: Two reviewers extracted the data independently. The methodological quality of the
trials was evaluated with respect to generation of the allocation sequence, allocation concealment, double blinding, and follow-up.
The outcomes were presented as relative risks (RR) or weighted mean differences (WMD) with 95% confidence intervals (CI).
MAIN RESULTS: We identified 27 randomised trials of bile acids for hepatitis B or C; none were of high methodological quality.
In one trial, ursodeoxycholic acid (UDCA) versus placebo for acute hepatitis B significantly reduced the risk of hepatitis
B surface antigen positivity at the end of treatment and serum HBV DNA level at the end of follow-up. In another trial, UDCA
versus no intervention for chronic hepatitis B significantly reduced the risk of having abnormal serum transaminase activities
at the end of treatment. Twenty-five trials compared bile acids (21 trials UDCA; four trials tauro-UDCA) versus placebo or
no intervention with or without co-interventions for chronic hepatitis C. Bile acids did not significantly reduce the risk
of having detectable serum HCV RNA (RR 0.99, 95% CI 0.91 to 1.07), cirrhosis, or portal and periportal inflammation score
at the end of treatment. Bile acids significantly decreased the risk of having abnormal serum alanine aminotransferase activity
at the end of treatment (RR 0.82, 95% CI 0.76 to 0.90) and follow-up (RR 0.91, 95% CI 0.85 to 0.98). Bile acids significantly
increased the Knodell score (WMD 0.20, 95% CI 0.08 to 0.31) at the end of treatment. No severe adverse events were reported.
We did not identify trials including patients with hepatitis A, acute C, D, or E. REVIEWER'S CONCLUSIONS: Bile acids lead
to a significant improvement in serum transaminase activities in hepatitis B and C. There is insufficient evidence either
to support or to refute effects on viral markers, mortality, incidence of cirrhosis, or liver histology. Trials with high
methodological quality are required.
Publication Types:
Review
PMID: 12804455 [PubMed - indexed for MEDLINE]
Am J Public Health. 2002 Oct;92(10):1619-28. Related Articles, Links
Chinese herbal medicine and interferon in the treatment of chronic hepatitis B: a meta-analysis of randomized, controlled
trials.
McCulloch M, Broffman M, Gao J, Colford JM Jr.
Pine Street Clinic, San Anselmo, CA, USA.
OBJECTIVES: This meta-analysis was conducted to examine the effectiveness of Chinese herbal medicine (either alone or
with interferon alfa) in treating chronic hepatitis B. METHODS: We searched the TCMLARS, AMED, CISCOM, EMBASE, MEDLINE, and
Cochrane Collaboration databases and then hand-searched the articles' bibliographies. RESULTS: Chinese herbal medicine significantly
increased seroreversion of HBsAg and was equivalent to interferon alfa in seroreversion of HBeAg and hepatitis B virus (HBV)
DNA; Chinese herbal medicine combined with interferon alfa significantly increased seroreversion of HBsAg, HBeAg, and HBV
DNA. The Chinese herbal medicine active component bufotoxin combined with interferon alfa significantly increased HBeAg and
HBV DNA seroreversion. The Chinese herbal medicine active component kurorinone was equivalent to interferon alfa in seroreversion
of HBeAg and HBV DNA. CONCLUSIONS: Although the quality of existing studies was poor, these data suggest that further trials
of Chinese Herbal Medicine and interferon in chronic hepatitis B infection are justified.
Publication Types:
Meta-Analysis
PMID: 12356611 [PubMed - indexed for MEDLINE]
Cochrane Database Syst Rev. 2002;(2):CD002234. Related Articles, Links
Update of:
Cochrane Database Syst Rev. 2002;(1):CD002234.
Ribavirin with or without alpha interferon for chronic hepatitis C.
Kjaergard LL, Krogsgaard K, Gluud C.
The Copenhagen Trial Unit, Centre for Clinical Intervention Research, H:S Rigshospitalet, Blegdamsvej 9, Dept. 7102, Copenhagen,
Denmark, DK-2100. kjaergard@ctu.rh.dk
BACKGROUND: Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon combination
therapy is presently considered the optimal treatment of interferon naive patients with chronic hepatitis C, but its role
in relapsers and non-responders to previous interferon therapy is not established. OBJECTIVES: To assess the efficacy and
safety of ribavirin alone or in combination with alpha interferon in interferon naive patients, relapsers, and non-responders
with chronic hepatitis C. SEARCH STRATEGY: Eligible trials were identified through searches on electronic databases: The Cochrane
Hepato-Biliary Group Controlled Trials Register (August 2001), The Cochrane Controlled Trials Register on The Cochrane Library
Issue 3, 2001, MEDLINE (1966 - August 2001), and EMBASE (1985 - August 2001). Manual searches of bibliographies and journals
were done as well as authors of trials and pharmaceutical companies producing ribavirin or interferon were contacted. SELECTION
CRITERIA: We included all randomised trials comparing ribavirin with or without alpha interferon versus no intervention, placebo,
or alpha interferon for chronic hepatitis C. DATA COLLECTION AND ANALYSIS: The primary outcome measures were the 'sustained'
(six months after treatment) virological response, and morbidity plus mortality. The secondary outcome measures were the 'end
of treatment' and 'sustained' biochemical response, the 'end of treatment' virologic response, histology, quality of life,
and adverse events. MAIN RESULTS: We included eight trials in which 271 patients were randomised to ribavirin versus placebo
or no intervention and 48 trials in which 6585 patients were randomised to interferon with or without ribavirin. Compared
with placebo or no intervention, ribavirin monotherapy had no significant effect on the virological response or histology
and only a transient effect on the biochemical response. Compared with interferon, combination therapy reduced the risk of
not having a sustained virological response by 26% in naive patients (relative risk (RR) 0.74; 95% confidence interval (CI)
0.70-0.78), 33% in relapsers (RR 0.67; 95% CI 0.57-0.78), and 11% in non-responders (RR 0.89; 95% CI 0.83-0.96). There was
no significant effect on morbidity plus mortality (Peto odds ratio 0.45; 95% CI 0.19-1.06). Irrespective of previous therapy,
combination therapy significantly reduced the risk of not having a sustained biochemical response (RR 0.76; 95% CI 0.59-0.84)
or improved histology (RR 0.67; 95% CI 0.56-0.81). Combination therapy also significantly increased the risk of treatment
discontinuation (RR 1.28; 95% CI 1.07-1.52) and several types of adverse events. REVIEWER'S CONCLUSIONS: Combination therapy
increased the number of naive patients, relapsers, and non-responders with a sustained virological, biochemical, or histological
response, but also the occurrence of adverse events.
Publication Types:
Review
PMID: 12076442 [PubMed - indexed for MEDLINE]
Cochrane Database Syst Rev. 2002;(2):CD000370. Related Articles, Links
Interferon for interferon naive patients with chronic hepatitis C.
Myers RP, Regimbeau C, Thevenot T, Leroy V, Mathurin P, Opolon P, Zarski JP, Poynard T.
Service d'Hepato-Gastroenterologie, Groupe Hospitalier Pitie-Salpetriere, Paris, France. drrobpmyers@hotmail.com
BACKGROUND: A previous meta-analysis of interferon therapy in naive patients with chronic hepatitis C has documented its
efficacy in achieving virologic clearance, and improving liver biochemistry and histology; however, since its publication
additional trials have been reported. OBJECTIVES: To evaluate the response to interferon in interferon naive patients with
chronic hepatitis C. The effect of treatment dose and duration, and the response in patients with cirrhosis and those with
normal aminotransferases was also investigated. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Cochrane Library
Issue 1, 1999), MEDLINE (January 1966 to December 1999), and reference lists were searched, and pharmaceutical companies were
contacted for unpublished trials. SELECTION CRITERIA: Randomised clinical trials comparing interferon with placebo, no treatment,
or different regimens of interferon were selected. Abstracts were excluded. DATA COLLECTION AND ANALYSIS: The primary outcome
measure was sustained disappearance of serum HCV RNA (virologic sustained response (SR)). Biochemical and end of treatment
responses, liver histology, and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and
Der Simonian and Laird. MAIN RESULTS: Fifty-four trials enrolling 6545 patients were included. Compared with no treatment,
interferon 3 MU thrice weekly for 12 months increased the probability of a virologic SR (Peto odds ratio (OR) 4.60; 95% confidence
interval (CI) 1.53 to 13.85). At this dosage and duration of therapy, the rate of virologic SR was 17% (95% CI 10 to 28%)
in interferon-treated patients versus 3% (95% CI 1 to 10%) in controls. A dose of 6 MU was more effective than 3 MU thrice
weekly (OR for 12 months treatment, 2.21; 95% CI 1.10 to 4.45), as were durations of 12 months or greater versus six months
(OR 1.87; 95% CI 1.30 to 2.67). Adverse events were more common with higher doses and prolonged durations of treatment. Compared
with no therapy, interferon increased the probability of histologic improvement (OR 9.22; 95% CI 5.69 to 14.94). The response
to interferon in cirrhotic patients (virologic SR, 17%; 95% CI 11 to 26%) was similar to that in non-cirrhotic patients. However,
interferon was no more effective than control in patients with normal aminotransferases. REVIEWER'S CONCLUSIONS: Interferon
is effective in achieving viral clearance and improving liver biochemistry and histology in interferon naive patients with
chronic hepatitis C. Higher doses and prolonged durations are more effective, but associated with more frequent adverse events.
Interferon is associated with similar benefits in patients with cirrhosis, but the efficacy in patients with normal aminotransferases
is unproven.
Publication Types:
Review
PMID: 12076394 [PubMed - indexed for MEDLINE]
Ann Intern Med. 2002 Feb 19;136(4):288-92. Related Articles, Links
Comment in:
Ann Intern Med. 2002 Dec 17;137(12):1012.
Summary for patients in:
Ann Intern Med. 2002 Feb 19;136(4):I48.
Surprisingly small effect of antiviral treatment in patients with hepatitis C.
Falck-Ytter Y, Kale H, Mullen KD, Sarbah SA, Sorescu L, McCullough AJ.
German Cochrane Institute, Stefan-Meier-Strasse 26, 79104 Freiburg, Germany.
BACKGROUND: The effect and applicability of interferon-based antiviral therapies in the general population of persons
with hepatitis C virus (HCV) infection are unknown. OBJECTIVE: To determine the applicability and usefulness of anti-viral
therapy in a metropolitan clinic population. DESIGN: Retrospective case series of consecutively referred patients. SETTING:
A teaching county hospital in Cleveland, Ohio. PATIENTS: 327 patients referred to a liver clinic after a positive result for
antibody against HCV on enzyme-linked immunosorbent assay (ELISA). MEASUREMENTS: Treatment rates; reasons for nontreatment.
RESULTS: 34 patients had no detectable HCV RNA. Of the remaining 293 patients, 72% were not treated for the following reasons:
37% did not adhere to evaluation procedures, 34% had medical or psychiatric contraindications, 13% had ongoing substance or
alcohol abuse, 11% preferred no treatment, and 5% had normal liver enzyme levels. Only 83 patients (28%) were treated; 13%
had a sustained viral response. CONCLUSION: Most patients with HCV infection are not candidates for interferon-based therapies;
alternative interventions should be sought for these patients.
PMID: 11848726 [PubMed - indexed for MEDLINE]
Aliment Pharmacol Ther. 2001 Dec;15(12):1899-905. Related Articles, Links
The efficacy of thymosin in the treatment of chronic hepatitis B virus infection: a meta-analysis.
Chan HL, Tang JL, Tam W, Sung JJ.
Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
BACKGROUND: Trials of thymosin treatment in chronic hepatitis B virus infection have been small and the results have been
inconsistent. AIM: To conduct a meta-analysis to evaluate the efficacy of thymosin treatment in chronic hepatitis B virus
infection. METHODS: Randomized controlled trials comparing thymosin for over 24 weeks vs. placebo (or usual care) in the treatment
of chronic hepatitis B virus infection were identified through MEDLINE, EMBASE and the Cochrane Register of Clinical Trials.
Biochemical (normalization of transaminases) and virological (loss of hepatitis B virus DNA and hepatitis B e antigen) responses
were analysed using the intention-to-treat method. The odds ratio was used to measure the magnitude of the efficacy. RESULTS:
Five trials (353 patients) were identified. The odds ratio (95% confidence interval) of the virological response of thymosin
over placebo at the end of treatment, 6 months post-treatment and 12 months post-treatment were 0.56 (0.2-1.52), 1.67 (0.83-3.37)
and 2.67 (1.25-5.68), respectively. There was an increasing trend of the virological response with time since the cessation
of thymosin treatment (P=0.02). There was no difference in the biochemical response between the thymosin and placebo groups
at the end of treatment, 6 months post-treatment and 12 months post-treatment. CONCLUSIONS: Thymosin is effective in suppressing
viral replication in chronic hepatitis B virus infection, but the effect is delayed until 12 months after the cessation of
treatment.
Publication Types:
Meta-Analysis
PMID: 11736720 [PubMed - indexed for MEDLINE]
J Viral Hepat. 2001 Sep;8(5):358-66. Related Articles, Links
Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review.
Liu J, Lin H, McIntosh H.
The Cochrane Hepato-Biliary Group, The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University
Hospital, Copenhagen, Denmark. Jianping_l@hotmail.com
To evaluate the efficacy and safety of genus Phyllanthus for chronic hepatitis B virus (HBV) infection we performed a
systematic review of randomized clinical trials. Randomized trials comparing genus Phyllanthus vs. placebo, no intervention,
general nonspecific treatment, other herbal medicine, or interferon treatment for chronic HBV infection were identified by
electronic and manual searches. Trials of Phyllanthus herb plus interferon (IFN) vs. IFN alone were also included. No blinding
and language limitations were applied. The methodological quality of trials was assessed by the Jadad scale plus allocation
concealment. Twenty-two randomized trials (n=1947) were identified. The methodological quality was high in five double-blind
trials and low in the 17 remaining trials. The combined results showed that Phyllanthus species had positive effect on clearance
of serum HBsAg (relative risk 5.64, 95% CI 1.85-17.21) compared with placebo or no intervention. There was no significant
difference on clearance of serum HBsAg, HBeAg and HBV DNA between Phyllanthus and IFN. Phyllanthus species were better than
nonspecific treatment or other herbal medicines for the clearance of serum HBsAg, HBeAg, HBV DNA, and liver enzyme normalization.
Analyses showed a better effect of the Phyllanthus plus IFN combination on clearance of serum HBeAg (1.56, 1.06-2.32) and
HBV DNA (1.52, 1.05-2.21) than IFN alone. No serious adverse event was reported. Based on this review Phyllanthus species
may have positive effect on antiviral activity and liver biochemistry in chronic HBV infection. However, the evidence is not
strong due to the general low methodological quality and the variations of the herb. Further large trials are needed.
Publication Types:
Meta-Analysis
PMID: 11555193 [PubMed - indexed for MEDLINE]
J Hepatol. 2004 Mar;40(3):491-500. Related Articles, Links
Complementary and alternative therapies in the treatment of chronic hepatitis C: a systematic review.
Coon JT, Ernst E.
Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter EX2
4NT, UK. jo.thompson-coon@pms.ac.uk
BACKGROUND/AIMS: Hepatitis C is an escalating global health problem. The recommended treatment regimen is associated with
considerable expense, adverse effects and poor efficacy in some patients. Complementary therapies are widely promoted for
and used by patients with hepatitis C. The aim is to systematically assess the efficacy of complementary therapies in treating
chronic hepatitis C. METHODS: Systematic searches were conducted in six databases, reference lists of all papers were checked
for further relevant publications and information was requested from experts. No language restrictions were imposed. RESULTS:
Twenty-seven eligible randomised clinical trials were located involving herbal products and supplements. No randomised clinical
trials were identified for any other complementary therapy. In 14 of the trials, patients received interferon-alpha in combination
with the complementary therapy. Less than half the trials (11/27) were of good methodological quality. Compared with the control
group, significant improvements in virological and/or biochemical response were seen in trials of vitamin E, thymic extract,
zinc, traditional Chinese medicine, Glycyrrhiza glabra and oxymatrine. CONCLUSIONS: We identified several promising complementary
therapies, although extrapolation of the results is difficult due to methodological limitations. More research is warranted
to establish the role of these and other therapies in the treatment of hepatitis C.
Publication Types:
Review
Review, Tutorial
PMID: 15123365 [PubMed - indexed for MEDLINE]
Phytomedicine. 2004 Feb;11(2-3):152-6. Related Articles, Links
Effects of lycopene-beadlet or tomato-powder feeding on carbon tetrachloride-induced hepatotoxicty in rats.
Kim Y, DiSilvestro R, Clinton S.
Human Nutrition, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210-1295, USA.
The carotenoid lycopene has been touted as possessing various antioxidant properties, but there are no demonstrations
that lycopene inhibits tissue injury due to acute oxidant stress. Thus, the present study examined the effects of intake of
lycopene or tomato extract, a rich source of lycopene, on acute liver injury caused by the oxidant carbon tetrachloride (CCl4).
Feeding with tomato extract (10% tomato powder), but not with lycopene (0.25% lycopene beadlets), partially inhibited CCl4-induced
hepatic injury based on the serum activities of sorbitol dehydrogenase and aspartate aminotransferase. No effect was seen
for either lycopene or tomato extract on serum beta-glucuronidase activity, a marker of lysosomal injury. We concluded that
tomato extract, but not lycopene, partially protected against acute liver injury due to chemically-induced oxidant stress.
PMID: 15070165 [PubMed - indexed for MEDLINE]
New Combo Treatment for Hepatitis C
WebMD Medical News Reviewed By Michael Smith, MD
on Wednesday, December 04, 2002
Dec. 4, 2002 -- People with chronic hepatitis C have a new drug treatment to consider. The FDA has approved the combination
of Pegasys and ribavirin to treat the disease in people who haven't been treated with interferon alpha, the standard drug
for hepatitis C. Pegasys, approved in October, is a type of interferon that stays in the body longer. Ribavirin is available
under the name brand Rebetol, and a second brand of ribavirin -- Copegus -- will be available in early 2003.
Combining Pegasys with the antiviral drug ribavirin can effectively suppress the virus more than half the time in patients
with the hard-to-treat type of hepatitis C (called genotype 1), and more than 80% of the time in those with the easier-to-treat
types (predominantly genotypes 2 and 3), according to Roche, the manufacturer of Pegasys. Genotype 1 is the most common in
the U.S., comprising about 85% of cases.
Here's more on the new drug approval:
Brand names: Pegasys; Copegus or Rebetol
Generic names: peginterferon alfa-2a; ribavirin
Manufacturer: Roche (Pegasys, Copegus), Schering (Rebetol)
How it is used: Pegasys injections of 180 micrograms once a week; ribavirin tablets in total daily doses of 800 to 1,200
mg (depending on a patient's weight) split between two doses.
Basis of approval: Approval was based on two phase III clinical trials. One compared the combination treatment on both
the easy- and hard-to-treat types of the virus for either 24 or 48 weeks, with lower doses of ribavirin in the shorter term.
The best results were for patients with the easier-to-treat virus (genotype non-1 hepatitis C) who were treated for 24 weeks
with a lower dose of ribavirin -- they had an 82% response rate. And the type 1 patients who had the higher ribavirin dose
for 48 weeks had a 51% response rate.
The other study compared the Pegasys-ribavirin combination with another combination -- interferon alpha-2b (not the peg
form) and ribavirin. The response rate was 53% for the Pegasys group and 44% for the regular interferon group.
A second form of pegylated interferon, Peg-Intron, was approved for use with ribavirin in August 2001.
Concerns: Patients who take interferon drugs should be monitored closely for signs of neuropsychiatric changes, such as
depression, autoimmune, blood, and infectious disorders. Ribavirin can cause birth defects and anemia.
N Z Med J 2001 Mar 23;114(1128):103-4 Related Articles, Links
Comment in:
N Z Med J. 2001 Mar 23;114(1128):101-2.
Interferon-alpha2a/ribaviran versus interferon-alpha2a alone for the retreatment of hepatitis C patients who relapse after
a standard course of interferon.
Chapman BA, Stace NH, Edgar CL, Bartlett SE, Frampton CM, Scahill SL, Jennings LC.
Canterbury Health, Christchurch. brucec@chhlth.govt.nz
AIM: To compare the efficacy of a descalating dose of interferon (48 weeks) versus a combination therapy of interferon
and ribavirin (24 weeks) in hepatitis C positive subjects who relapsed within six months of cessation of a standard six month
course of interferon three million units thrice weekly. METHODS: All 32 subjects had biopsy proven chronic hepatitis C, were
PCR positive and had elevated transaminase enzymes at least one and a half times the upper limit of normal. Subjects were
randomly assigned to either a descalating dose of interferon-alpha-2a; six million units thrice weekly for 24 weeks followed
by 3 MIU 3x for 24 weeks or interferon three million units thrice weekly for 24 weeks plus ribavirin 1,000 mg/day for 12 weeks.
A complete virological response was defined as a negative PCR for HCV RNA at 24 weeks after cessation of therapy. RESULTS:
Sixteen patients were assigned to each arm and the sustained virological response was 50% for both the interferon and combination
therapy arm (pNS). The biochemical response correlated with the virological response; 7/8 virological responders in the interferon
alone had normalisation of transaminase 24 weeks post treatment as did 8/8 of those in the combination arm. One patient withdrew
from treatment in the descalating interferon group and three required dose reduction. No subjects in the combination arm discontinued
therapy but dose reduction was required in three subjects. CONCLUSION: High dose descalating interferon-alpha 2a and a combination
of interferon-alpha 2a and ribavirin were effective in achieving a sustained virological response in 50% of subjects who had
relapsed after a standard six month course of interferon.
Publication Types: Clinical Trial
Randomized Controlled Trial
PMID: 11346153 [PubMed - indexed for MEDLINE]
Am Clin Lab 2002 May;21(4):19-21 Related Articles, Links
The use of alternative medicine in the treatment of hepatitis C.
Bean P.
Rogers Memorial Hospital, Oconomowac, WI, USA. pambean@charter.net
More than one-third of Americans use herbs for health purposes, yet patients and physicians usually lack accurate information
about safety and efficacy of herbal remedies. In recent years, there has been a substantial increase in the use of so-called
complementary and alternative therapies by patients with liver disease. Medical professionals and laboratorians need to be
informed about popular alternative therapies and be open-minded to the possibility that some benefit may come from some therapies
currently regarded as alternative. Silymarin extracted from the milk thistle is most widely subscribed to as a remedy for
liver diseases. The beneficial effects of silymarin are most often seen in the patients who had cirrhosis as a result of alcohol
abuse. An ongoing clinical trial will provide some insight as to whether milk thistle directly affects HCV. Silymarin has
a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published.
The active component of licorice root, glycyrrhizin, has been shown to reduce alanine transaminase and aspartate transaminase
values in the serum. This protective function has recently been explained as the inhibitory effects of glycyrrhizin on immune-mediated
cytotoxicity against hepatocytes and on nuclear factor (NF)-kappa B, which activates genes encoding inflammatory cytokines
in the liver. Finally, some patients with hepatitis C take St. John's Wort and ginger to treat the side effects caused by
interferon therapy. An excellent review of this subject was recently published by the NCCAM.
Publication Types:
Review Review, Tutorial
PMID: 12087634 [PubMed - indexed for MEDLINE]
Ann Intern Med 2002 May 21;136(10):747-57 Related Articles, Links
Approach to the patient with chronic hepatitis C virus infection.
Herrine SK.
Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Chronic hepatitis C virus (HCV) infection is common and often asymptomatic. Antibodies against HCV are a highly sensitive
marker of infection. Molecular testing for HCV is used to confirm a positive result on antibody testing and to provide prognostic
information for treatment; however, quantitative HCV RNA does not correlate with disease severity or risk for progression.
Chronic HCV infection is most frequently associated with remote or current intravenous drug use and blood transfusion before
1992, although as many as 20% of infected patients have no identifiable risk factor. In an estimated 15% to 20% of persons
infected with HCV, the infection progresses to cirrhosis; alcohol intake is an important cofactor in this progression. Most
specialists prefer to include an examination of liver histology in the management of patients with chronic HCV infection to
aid prognostic and treatment decisions. The current standard of pharmacologic treatment of chronic HCV is weekly subcutaneous
peginterferon in combination with daily oral ribavirin, which results in sustained virologic response in approximately 55%
of chronically infected patients. Side effects of interferon therapy include myalgias, fever, nausea, irritability, and depression.
The cost-effectiveness of interferon therapy is similar to that of many commonly accepted medical interventions. The primary
care physician serves a vital role in identifying patients with chronic HCV infection, educating patients about risk factors
for transmission, advising patients about the avoidance of alcohol, and aiding patients in making treatment decisions.
PMID: 12020143 [PubMed - indexed for MEDLINE]
Gastroenterol Nurs 2001 Mar-Apr;24(2):95-7 Related Articles, Links
Milk thistle and the treatment of hepatitis.
Giese LA.
Gastroenterology nurses and associates will find it helpful to be informed about milk thistle (silybum marianum), a popular,
safe and promising herb used by patients with liver disease. Silymarin is a derivative from the milk thistle plant with few
side effects that has been safely used for centuries to treat liver ailments. Since the 1970s, there has been a reemergence
of the marketing and use of silymarin. Research results of some small studies suggest silymarin has hepatoprotective, antiinflammatory,
and regenerative properties producing a beneficial effect for some types of hepatitis. It is unclear, however, whether silymarin
might interfere with the effect of interferon or ribavirin. A well-designed, placebo-controlled study of a larger population
is needed. It is certainly encouraging that a large collaborative study is currently underway for milk thistle therapy in
hepatitis C. This study is funded by NCCAM, the National Institute of Allergy and Infectious Diseases (NIAID), and the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Research updates are available online at www.nccam.nih.gov
and through the NCCAM Clearinghouse at 1-888-644-6226.
Publication Types:
Review, Tutorial
PMID: 11847735 [PubMed - indexed for MEDLINE]
NCCAM Clearinghouse article
Introduction
Hepatitis C is a serious communicable (contagious) disease of the liver that is caused by the hepatitis C virus (HCV).
Hepatitis C and its implications were identified only recently. There still is much to learn about the disease, the virus
that causes it, and treatment options, both conventional and alternative.
About 3 million Americans are infected with HCV, and many of them do not even know they have it. Other forms of viral
hepatitis usually resolve without treatment. But most people with HCV, 85 percent, develop chronic (frequent or long-lasting)
hepatitis C. The majority of people infected with HCV show no symptoms for up to 20 to 30 years. During that time, though,
the infection may be slowly damaging the person's liver.
The virus can be found in a number of organs of the body. However, the infection is spread mainly by contact with the
blood of an infected person. Once a person is infected, the body's immune (disease-fighting) system cannot combat the virus
very well.
Most people with chronic hepatitis C develop long-term liver disease, which interferes with the liver's ability to work
properly. Some patients eventually develop cirrhosis (scarring of the liver); some get liver cancer; and some even die from
liver disease.
Repeated injections of regular ("conventional") drugs, like interferon, currently available to treat chronic
hepatitis C get rid of the virus only in approximately 30 to 40 percent of infected people. In addition, these drugs can produce
unbearable side effects. So, many people are looking to complementary and alternative therapies for help.
Alternative Care
No complementary medicine or alternative medicine therapies have been scientifically proven to cure or even ease symptoms
of hepatitis C.
However, some people are turning to herbs for relief. They use herbs either to help with hepatitis itself or to deal with
side effects of interferon. These harmful side effects can include: sudden hearing loss; anemia and other forms of low blood
cell counts; headaches; heart, eye, liver, or kidney problems; and disorders of the mind, including depression. Among potential
herbal therapies (including licorice root, ginseng, ginger, and St. John's wort) for hepatitis C, the most promising alternative
treatment seems to be the herb commonly called milk thistle.
Preliminary studies in animals show that milk thistle may help protect the liver from injury by a variety of toxins ("poisons"
such as drugs, viruses, alcohol, radiation, and poisonous mushrooms) and limit the damage from them.1,2 To date, the most
reliable, and also quite preliminary, studies on people show that milk thistle does not cure liver disease, but that it may
improve the way the liver works in patients with cirrhosis.1 However, there is no current evidence to indicate that milk thistle
directly affects HCV.
In Germany, where many herbs are regulated and prescribed like drugs, health authorities have approved milk thistle as
a complementary treatment (given in addition to conventional drugs) for cirrhosis, hepatitis, and similar liver conditions.2
But a great deal of research still is needed before this alternative therapy could be considered a standard treatment option
in the United States.
Top
Milk Thistle
Milk thistle originally is from Europe, but now it also is grown in the United States. Its scientific name is Silybum
marianum. The ingredient that experts believe is responsible for its medicinal qualities is called silymarin. Silymarin is
found in the fruits of the milk thistle plant. Studies in animals have shown that this active ingredient promotes the following
activities:
Liver Cell Growth: Silymarin appears to promote the growth of some types of cells in the liver.1,2
Antioxidation: Silymarin may be an effective "antioxidant," which means it may help fight a destructive chemical
process in the body known as "oxidation." In oxidation, harmful substances produced in the body (called free radicals)
can damage cells. Some studies suggest that silymarin can prevent these substances from damaging liver cells.1,3,4
Antihepatotoxic Activity: Studies suggest that silymarin can block various types of toxins from entering and injuring
liver cells.1,2,5
Inflammation Inhibition: Silymarin is thought to prevent inflammation (swelling) of the liver; this may be described as
displaying anti-inflammatory properties.1
Milk thistle is not used to prevent HCV from causing liver disease. Rather, it is used with the hope that it would minimize
the damage to the liver that HCV can cause.
Top
Studies of Milk Thistle in People
Although studies in animals provide a good deal of information on potential new treatments, studies in humans are needed
before it can be determined if these therapies are appropriate, safe, and effective in people. The most rigorous type of study
to establish a scientific basis for use of a new therapy in people is a randomized, double-blind, placebo-controlled (RDBPC)
trial.
Although not focused primarily on HCV disease, the most relevant existing research data regarding milk thistle's use as
a therapy for hepatitis comes from two RDBPC trials of silymarin's effects on cirrhosis.1 The two studies produced conflicting
results.
The first, reported in 1989, examined 170 patients with cirrhosis from various causes, including alcohol abuse.6 Approximately
half (87) of the patients received silymarin (140 milligrams 3 times a day for 2 years). The others (83 patients) received
a placebo. Because 24 patients dropped out of the study, a total of 146 patients (73 in each group) finished the 2-year study.
The doctors in this study noted that the number of patients who died in the 4 years after the study was 31 percent lower
in the group that received the silymarin than in the group of patients who received the placebo. The beneficial effects of
silymarin were especially seen in the patients who had cirrhosis as a result of alcohol abuse. The doctors did not report
that any patients experienced side effects from silymarin treatment.
A more recent RDBPC trial, however, did not find silymarin to have any significant benefits for patients with cirrhosis.7
In this study, reported in 1998, doctors examined 200 patients with cirrhosis caused by alcohol abuse. Approximately half
(103) of the patients received silymarin (150 milligrams 3 times a day for 2 years). The other half (97) received a placebo.
A total of 125 patients (57 in the treatment group and 68 in the placebo group) finished the 2-year study. To measure effectiveness,
the doctors measured (1) time to death and (2) the worsening of the disease.
Survival was similar in both the silymarin and placebo groups, and silymarin did not seem to improve the course of the
disease in the treatment group. The doctors who performed the experiment did not note side effects in any of the patients.
Although small, one randomized controlled trial on hepatitis patients suggests that a specific component in silymarin
may be beneficial in managing chronic hepatitis.8 In this study, reported in 1993, 10 patients with chronic hepatitis were
assigned to the treatment group and 10 others were assigned to the placebo group. The treatment group received 240 milligrams
of silybin, a component of silymarin, two times a day for 1 week. The results of tests that measure how well the liver is
functioning showed significant improvement in the treatment group, suggesting that silybin may help treat chronic hepatitis.
Milk thistle in the treatment of liver disease needs to be studied further. Fortunately, negative side effects have not
yet been reported, and this herbal therapy may be much less expensive than conventional drug therapies. Yet, it should be
mentioned that conventional therapies have been proven to work in a substantial portion of patients.
Because milk thistle does not dissolve well in water, the herb is not effective in the form of a tea. It currently is
marketed in the United States as a dietary supplement in the form of capsules containing 200 milligrams of a concentrated
extract with 140 milligrams of silymarin.
Top
Other Herbs That May Help
Licorice Root: Herbalists use tea made with licorice root to manage some of the effects hepatitis has on the liver. The
scientific name for licorice root is Glycyrrhiza glabra, and its active component is called glycyrrhizin. Studies suggest
that licorice root displays antiviral and anti-inflammatory properties.9
Licorice root does come with a warning, however. If taken regularly (more than 3 grams of licorice root a day for more
than 6 weeks, or more than 100 milligrams of glycyrrhizin a day), this herb can cause the following conditions in some people:
high blood pressure, sodium and water retention, low potassium levels in the bloodstream, and disturbance of an important
electrolyte balancing system in the body.
Signs and symptoms of excessive licorice root consumption may include headache, sluggishness, puffiness and swollen ankles,
and even heart failure or cardiac arrest (when the heart suddenly stops beating).10
Glycyrrhizin has been used in Japan for more than 20 years as a treatment for chronic hepatitis.9,11 In a 1998 review11
of several randomized controlled trials, researchers reported that treatment with glycyrrhizin is effective in easing liver
disease in some people. Several of the trials reviewed indicated improvements in liver tissue that had been damaged by hepatitis.
Some of them also showed improvements in how well the liver does its job.
A 1997 experiment suggested that glycyrrhizin also may help prevent the development of liver cancer in patients with chronic
hepatitis C.12 The use of glycyrrhizin as a complementary therapy (in addition to conventional use of interferon drugs) has
been studied, but no significant benefit has been found yet.13,14
Ginseng: Tests on animals and on human tissues suggest that ginseng may help the body's disease-fighting and glandular
systems. Tests in small animals also suggest that ginseng may help improve the way the liver works and reduce damage to liver
tissue caused by hepatitis and similar conditions.15,16,17 However, a search of the current literature shows no studies in
people that test ginseng's helpfulness for hepatitis. Only one study, conducted in Italy, shows that ginseng may be helpful
for elderly people with liver conditions similar to hepatitis.18
There are two true ginsengs: American ginseng (Panax quinquefolius) and Asian ginseng (Panax ginseng), which includes
Chinese, Japanese, and Korean ginseng. Siberian ginseng (Eleutherococcus senticosus) is not a true ginseng.1,19 It is hard
to get authentic ginseng products. Companies that market herbs for sale have poor quality control, so the quality of the different
brands varies widely. A 1990 analysis of 54 available ginseng products revealed that 85 percent of them contained little or
no ginseng at all!19 Ginseng most often is taken as a tea.
Herbs That May Ease Interferon's Effects
Ginger: For 2,500 years, the Chinese have used ginger (Zingiber officinale) to treat nausea.1 Some, but not all, research
studies confirm that ginger may reduce nausea.1 This herb may relieve nausea and vomiting caused by interferon drug therapy
in some patients with hepatitis C. Ginger generally is recognized as safe and is not known to cause any serious side effects.
Ginger is relatively inexpensive and readily available. It most commonly is taken in the form of a tea.
St. John's Wort: Some patients with hepatitis C take the herb St. John's wort (Hypericum perforatum) to treat depression
caused by interferon drug therapy. Although St. John's wort is not a proven treatment for depression, studies have shown that
it does have antidepressive effects over the short term. Although research largely has been done using capsules of this herb,
St. John's wort also is taken as a tea. There is no proof yet that St. John's wort is effective and safe over the long term.
St. John's wort does not require a prescription, and it is less expensive and may have fewer side effects than prescription
antidepressant drugs.20 Tests in people reveal it may cause side effects such as fatigue, dry mouth, dizziness, digestive
tract symptoms, and increased sensitivity to sunlight.
If You Have Hepatitis C
Get an accurate diagnosis from your doctor. Hepatitis C infection can be diagnosed only by using sophisticated blood tests
available to all doctors.
Tell your doctor about all of the medications you are taking, even any over-the-counter drugs or herbs or other alternative
therapies you may be using. Because the liver plays a key role in processing drugs, alcohol, and toxins in the bloodstream,
medications, alcoholic beverages, and certain herbs can make the disease worse.
Consider being vaccinated against hepatitis A and B.21 Unlike hepatitis A and B, previous infection with HCV does not
make you immune to it in the future.21 Infection with HCV also does not prevent you from becoming infected with other types
of hepatitis (hepatitis A, B, D, E, and G).
Do not try to treat the disease yourself.
Do not donate blood.
Do not drink alcohol, because it can further damage your already diseased liver.
Do not share needles if you use injection drugs.
For More Information
For more information about hepatitis C, you may want to contact the following organizations:
American Liver Foundation
1-800-465-4837 (1-800-GO-LIVER) (Toll-Free)
www.liverfoundation.org (Web Site)
Hepatitis Branch, Centers for Disease Control and Prevention
1-888-443-7232 (1-888-4HEPCDC) (Toll-Free)
www.cdc.gov/ncidod/diseases/hepatitis (Web Site)
Hepatitis Foundation International
1-800-891-0707 (Toll-Free)
www.hepfi.org (Web Site)
National Digestive Diseases Information Clearinghouse
301-654-3810
www.niddk.nih.gov/health/digest/nddic.htm (Web Site)
For more information about alternative therapies for hepatitis C, you may wish to contact the following organizations:
American Botanical Council
www.herbalgram.org (Web Site)
Herb Research Foundation
303-449-2265 (Telephone)
www.herbs.org (Web Site)
Top
References
1. O'Hara, M., Kiefer, D., Farrell, K., and Kemper, K. "A Review of 12 Commonly Used Medicinal Herbs." Archives
of Family Medicine. 1998. 7(6):523-36.
2. Tyler, V.E. "Milk Thistle." In: The Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies,
3rd ed., edited by M.C. Smith. Binghamton, NY: Pharmaceutical Products Press, 1993. pp. 209-10.
3. Garciapina, M.P., Perez-Alvarez, V., and Mourelle, M. "Silymarin Protects Against Paracetamol-Induced Lipid Peroxidation
and Liver Damage." Journal of Applied Toxicology. 1992. 12(6):439-42.
4. Letteron, P., Labbe, G., Degott, C., Berson, A., Fromenty, B., Delaforge, M., Larrey, D., and Pessayre, D. "Mechanism
for the Protective Effects of Silymarin Against Carbon Tetrachloride-Induced Liver Peroxidation and Hepatotoxicity in Mice.
Evidence that Silymarin Acts Both as an Inhibitor of Metabolic Activation and as a Chain-Breaking Antioxidant." Biochemical
Pharmacology. 1990. 39(12):2027-34.
5. Davila, J.C., Lenherr, A., and Acosta, D. "Protective Effect of Flavonoids on Drug-Induced Hepatotoxicity In Vitro."
Toxicology. 1989. 57(3):267-86.
6. Ferenci, P., Dragosics, B., Dittrich, H., Frank, H., Benda, L., Lochs, H., Meryn, S., Base, W., and Schneider, B. "Randomized
Controlled Trial of Silymarin Treatment in Patients with Cirrhosis of the Liver." Journal of Hepatology. 1989. 9(1):105-13.
7. Pares, A., Planas, R., Torres, M., Caballeria, J., Viver, J.M., Acero, D., Panes, J., Rigau, J., Santos, J., and Rodes,
J. "Effects of Silymarin in Alcoholic Patients with Cirrhosis of the Liver: Results of a Controlled, Double-Blind, Randomized
and Multicenter Trial." Journal of Hepatology. 1998. 28(4):615-21.
8. Buzzelli, G., Moscarella, S., Giusti, A., Duchini, A., Marena, C., and Lampertico, M. "A Pilot Study of the Liver
Protective Effect of Silybin-Phosphatidylcholine Complex (IdB1016) in Chronic Active Hepatitis." International Journal
of Clinical Pharmacology, Therapy, and Toxicology. 1993. 31(9):456-60.
9. Werbach, M.R. and Murray, M.T. Botanical Influences on Illness: A Sourcebook of Clinical Research. Tarzana, CA: Third
Line Press, 1994.
10. Tyler, V.E. "Licorice." In: The Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies,
3rd ed., edited by M.C. Smith. Binghamton, NY: Pharmaceutical Products Press, 1993. pp. 197-9.
11. van Rossum, T.G., Vulto, A.G., de Man, R.A., Brouwer, J.T., and Schalm, S.W. "Review Article: Glycyrrhizin as
a Potential Treatment for Chronic Hepatitis C." Alimentary Pharmacology and Therapeutics. 1998. 12(3):199-205.
12. Arase, Y., Ikeda, K., Murashima, N., Chayama, K., Tsubota, A., Koida, I., Suzuki, Y., Saitoh, S., Kobayashi, M., and
Kumada, H. "The Long-Term Efficacy of Glycyrrhizin in Chronic Hepatitis C Patients." Cancer. 1997. 79(8):1494-500.
13. Abe, Y., Ueda, T., Kato, T., and Kohli, Y. "Effectiveness of Interferon, Glycyrrhizin Combination Therapy in
Patients with Chronic Hepatitis C." Nippon Rinsho (Japanese Journal of Clinical Medicine). 1994. 52(7):1817-22.
14. Okuno, T., Arai, K., and Shindo, M. "Efficacy of Interferon Combined Glycyrrhizin Therapy in Patients with Chronic
Hepatitis C Resistant to Interferon Therapy." Nippon Rinsho (Japanese Journal of Clinical Medicine). 1994. 52(7):1823-7.
15. Davydov, V.V., Molokovskii, D.S., and Limarenko, A.I. "Efficacy of Ginseng Drugs in Experimental Insulin-Dependent
Diabetes and Toxic Hepatitis." Patologicheskaia Fiziologiia i Eksperimentalnaia Terapiia. 1990. (5):49-52.
16. Jeong, T.C., Kim, H.J., Park, J.I., Ha, C.S., Park, J.D., Kim, S.I., and Roh, J.K. "Protective Effects of Red
Ginseng Saponins Against Carbon Tetrachloride-Induced Hepatotoxicity in Sprague Dawley Rats." Planta Medica. 1997. 63(2):136-40.
17. Matsuda, H., Samukawa, K., and Kubo, M. "Anti-Hepatitic Activity of Ginsenoside Ro." Planta Medica. 1991.
57(6):523-6.
18. Zuin, M., Battezzati, P.M., Camisasca, M., Riebenfeld, D., and Podda, M. "Effects of a Preparation Containing
a Standardized Ginseng Extract Combined with Trace Elements and Multivitamins Against Hepatotoxin-Induced Chronic Liver Disease
in the Elderly." Journal of International Medical Research. 1987. 15(5):276-81.
19. Tyler, V.E. "Ginseng and Related Herbs." In: The Honest Herbal: A Sensible Guide to the Use of Herbs and
Related Remedies, 3rd ed., edited by M.C. Smith. Binghamton, NY: Pharmaceutical Products Press, 1993. pp. 153-8.
20. Philipp, M., Kohnen, R., and Hiller, K.O. "Hypericum Extract Versus Imipramine or Placebo in Patients with Moderate
Depression: Randomised Multicentre Study of Treatment for Eight Weeks." British Medical Journal. 1999. 319(7224):1534-9.
21. National Institutes of Health. Management of Hepatitis C. NIH Consensus Statement Online. March 24-26, 1997. 15(3):1-41.
NIH Consensus Statement No. 5. odp.od.nih.gov/consensus/cons/105/105_statement.htm.
Cochrane Database Syst Rev 2001;(4):CD003183 Related Articles, Links
Medicinal herbs for hepatitis C virus infection.
Liu JP, Manheimer E, Tsutani K, Gluud C.
The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University
Hospital, Dept. 7701, H:S Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark, DK-2100. Jianping l@hotmail.com
BACKGROUND: Hepatitis C virus (HCV) infection is a serious health problem world-wide. Medicinal herbs are increasingly
being used for hepatitis C. OBJECTIVES: To assess the efficacy and safety of medicinal herbs for hepatitis C virus infection.
SEARCH STRATEGY: Searches were applied to The Controlled Trial Registers of The Cochrane Hepato-Biliary Group, The Cochrane
Complementary Medicine Field, and The Cochrane Library as well as MEDLINE, EMBASE, BIOSIS, Chinese and Japanese databases.
Five Chinese journals and one Japanese journal were handsearched. No language restriction was used. SELECTION CRITERIA: Randomised
clinical trials comparing medicinal herbs (single herb or compound of herbs) versus placebo, no intervention, general non-specific
treatment, other herbal medicine, or interferon and/or ribavirin treatment. Trials of medicinal herbs plus interferon and/or
ribavirin versus interferon and/or ribavirin alone were also included. Trials could be double-blind, single-blind, or unblinded.
DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. The methodological quality of the trials
was evaluated using the generation of allocation sequence, allocation concealment, double blinding, and the Jadad-scale. The
outcomes were presented as relative risk or weighted mean difference, both with 95% confidence interval. MAIN RESULTS: Ten
randomised trials, including 517 patients with mainly chronic hepatitis C, evaluated ten different medicinal herbs versus
various control interventions (four placebo, four interferon, two other herbs). The methodological quality was considered
adequate in four trials and inadequate in six trials. Compared with placebo in four trials, none of the medicinal herbs showed
positive effects on clearance of serum HCV RNA or anti-HCV antibody or on serum liver enzymes, except one short-term trial
in which a silybin preparation showed a significant effect on reducing serum aspartate aminotransferase and gamma-glutamyltranspeptidase
activities. The herbal compound Bing Gan Tang combined with interferon-alpha showed significantly better effects on clearance
of serum HCV RNA (relative risk 2.54; 95% confidence interval 1.43 to 4.49) and on normalisation of serum alanine aminotransferase
activity (relative risk 2.54; 95% confidence interval 1.43 to 4.49) than interferon-alpha monotherapy. The herbal compound
Yi Zhu decoction showed a significant effect on clearance of serum HCV RNA and normalisation of ALT levels compared to glycyrrhizin
plus ribavirin. Yi Er Gan Tang showed a significant effect on normalising serum alanine aminotransferase compared to silymarin
plus glucurolactone. There was no significant efficacy of the other examined herbs. The herbs were associated with adverse
events. REVIEWER'S CONCLUSIONS: There is no firm evidence of efficacy of any medicinal herbs for HCV infection. Medicinal
herbs for HCV infection should not be used outside randomised clinical trials.
PMID: 11687177 [PubMed - indexed for MEDLINE]
Eur J Med Res 2001 Sep 28;6(9):399-405 Related Articles, Links
Effects of a mistletoe preparation with defined lectin content on chronic hepatitis C: an individually controlled cohort
study.
Huber R, Ludtke R, Klassen M, Muller-Buscher G, Wolff-Vorbeck G, Scheer R.
Center for Complementary Medicien, Department of Internal Medicine II, University Hospital Freiburg, Germany. rhuber@med1.ukl.uni-freiburg.de
Despite advances in the therapy of chronic hepatitis C for some hepatitis C virus (HCV) genotypes interferon and ribavirin
combination therapy is effective in less than 50% of patients. Abnobaviscum Quercus (AQ) is a mistletoe preparation containing
defined amounts of mistletoe lectins (ML). It has shown immunomodulatory properties in vitro and in vivo. In small clinical
trials AQ resulted, within an anthroposophical treatment concept, in a biochemical or virological response in up to 40% of
patients with chronic hepatitis C. In order to evaluate the effect of this preparation we conducted an individually controlled
cohort study. 25 patients with chronic hepatitis C (mean duration 147 +/- 80 months) and elevated alanine aminotransferase
(ALT) levels were included in the study. As control they were observed for 6 months pre-treatment. This pre-treatment period
was followed by 6 months of active treatment in which the mistletoe preparation was subcutaneously injected three times a
week. Main outcome parameters were normalization of ALT and viral load. Hepatitis C associated signs and symptoms like tiredness,
fullness in the right upper abdomen and musculoskeletal pain were assessed monthly in a standardized questionnaire. All 25
patients completed the study and most of the patients wanted to continue treatment. Mean duration of treatment was 9.1 months.
None of the patients had complete or partial normalization of ALT or HCV RNA levels during pre-treatment or treatment period.
Mean ALT did not change during the study. Tiredness, fullness in the right upper abdomen and musculoskeletal pain were present
in 18, 8 and 4 patients respectively. They significantly improved within two months of treatment. A significant eosinophilia
(p=0.0001) occurred between month 2 and 6 during treatment. 9 month treatment with a ML containing mistletoe preparation has
no effect on viral load or ALT as markers of activity in patients with chronic hepatitis C. However, frequency and intensity
of clinical signs and symptoms in our patients decreased significantly, similar to reports of improved quality of life in
tumour patients treated with such preparations. A significant eosinophilia suggests that ML containing mistletoe preparations
induce a T-helper 2 immune response.
Publication Types:
Clinical Trial Controlled Clinical Trial
PMID: 11669085 [PubMed - indexed for MEDLINE]
Am J Chin Med 2000;28(3-4):351-60 Related Articles, Links
Clinical and pharmacological studies on liver diseases treated with Kampo herbal medicine.
Cyong JC, Ki SM, Iijima K, Kobayashi T, Furuya M.
Department of Bioregulatory Function, Graduate School of Medicine, University of Tokyo, Japan.
Hepatitis C virus (HCV) infection frequently causes chronic hepatitis, which is linked to the development of liver cirrhosis
and hepatocellular carcinoma. Most physicians who practice Kampo medicine in Japan have observed that Kampo medicine can be
as effective as interferon therapy in the treatment of chronic hepatitis C. In the present study, to evaluate the effect of
Kampo medicine on chronic hepatitis C, clinical treatment was assessed in short-term and long-term study, and it was shown
that ninjin-yoei-to (Formula ginseng compositae: TJ-108) was very effective. Therefore, to find the most active herbal component
of TJ-108 in the treatment of HCV, Citrus Unshiu Peel, Schisandra Fruit, and Polygala Root, which are specific to TJ-108,
were screened using an in vitro HCV infection model. Among the three herbs, Schisandra Fruit was found to be most active.
In the next step, Gomisin A, an active component of Schisandra Fruit, was studied using an in vitro model with MOLT-4 cells
and an animal model of immunologically induced acute hepatic failures. It is concluded that the therapeutic effect of TJ-108
on chronic hepatitis C is from the inhibitory effect on HCV infection, and also from the protective effect on immunological
hepatopathy of Schisandra Fruit and its lignan component, Gomisin A.
PMID: 11154048 [PubMed - indexed for MEDLINE]
Phytother Res 2000 Nov;14(7):510-6 Related Articles, Links
Inhibitory effects of sudanese medicinal plant extracts on hepatitis C virus (HCV) protease.
Hussein G, Miyashiro H, Nakamura N, Hattori M, Kakiuchi N, Shimotohno K.
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
One hundred fifty-two methanol and water extracts of different parts of 71 plants commonly used in Sudanese traditional
medicine were screened for their inhibitory effects on hepatitis C virus (HCV) protease (PR) using in vitro assay methods.
Thirty-four extracts showed significant inhibitory activity (>/=60% inhibition at 100 microg/mL). Of these, eight extracts,
methanol extracts of Acacia nilotica, Boswellia carterii, Embelia schimperi, Quercus infectoria, Trachyspermum ammi and water
extracts of Piper cubeba, Q. infectoria and Syzygium aromaticum, were the most active (>/=90% inhibition at 100 microg/mL).
From the E. schimperi extract, two benzoquinones, embelin (I) and 5-O-methylembelin (II), were isolated and found as potent
HCV-PR inhibitors with IC(50) values of 21 and 46 microM, respectively. Inhibitory activities of derivatives of I against
HCV-PR as well as their effects on other serine proteases were also investigated.Copyright 2000 John Wiley & Sons, Ltd.
PMID: 11054840 [PubMed - indexed for MEDLINE]
Altern Med Rev 2000 Aug;5(4):355-71 Related Articles, Links
Hepatitis C; a retrospective study, literature review, and naturopathic protocol.
Milliman WB, Lamson DW, Brignall MS.
Naturopathic Medicine Program, Bastyr University, Kenmore, WA, USA. doctorwbm@earthlink.net
The standard medical treatment of hepatitis C infection is only associated with sustained efficacy in a minority of patients.
Therefore, the search for other treatments is of utmost importance. Several natural products and their derivatives have demonstrated
benefit in the treatment of hepatitis C and other chronic liver conditions. Other herbal and nutritional supplements have
mechanisms of action that make them likely to be of benefit. This article presents comprehensive protocol, including diet,
lifestyle, and therapeutic interventions. The authors performed a retrospective review of 41 consecutive hepatitis C patients.
Of the 14 patients with baseline and follow-up data who had not undergone interferon therapy, seven had a greater than 25-percent
reduction in serum alanine aminotransferase (ALT) levels after at least one month on the protocol. For all patients reviewed,
the average reduction in ALT was 35 U/L (p=0.026). These data appear to suggest that a conservative approach using diet and
lifestyle modification, along with safe and indicated interventions, can be effective in the treatment of hepatitis C. Controlled
trials with serial liver biopsy and viral load data are necessary to confirm these preliminary findings.
Publication Types:
Review
Review, Tutorial
PMID: 10956381 [PubMed - indexed for MEDLINE]
Full text available at: www.hepcbc.ca/Naturopathic%20Protocol.pdf
Altern Med Rev 1999 Aug;4(4):220-38 Related Articles, Links
Hepatitis C: epidemiology and review of complementary/alternative medicine treatments.
Patrick L.
Hepatitis C is emerging as a serious worldwide problem. In the United States the current mortality figures may triple
in the next ten years, rivaling HIV. The disease has a latency of 10-30 years and symptoms or signs may not appear until cirrhosis
is evident. Adequate diagnosis, including liver biopsy, is essential in assessing the current stage of the viral infection
and the need for treatment. Hepatitis C may manifest as hepatic fibrosis, cirrhosis, hepatocellular carcinoma, lichen planus,
glomerulonephritis, mixed cryoglobulinemia, or porphyria. The hepatic damage is due both to the cytopathic effect of the virus
and the inflammatory changes secondary to immune activation. The use of the botanical components glycyrrhizin, catechin, silymarin
and phytosterols, and the antioxidants N-acetylcysteine and vitamin E are reviewed for their efficacy in treating chronic
hepatitis and affecting liver damage.
Publication Types:
Review
Review, Tutorial
PMID: 10468647 [PubMed - indexed for MEDLINE]
J Altern Complement Med 1997 Spring;3(1):77-82 Related Articles, Links
Two cases of hepatitis C treated with herbs and supplements.
Stern E.
The treatment of two cases of hepatitis C using herbal medicine and nutritional supplements is presented. The selection
of medicinals was based upon both biomedical findings and traditional Chinese medical diagnosis. The text describes the course
of each patient's illness documented both subjectively and objectively using blood values and traditional Chinese medicine
analysis as parameters. Explanation and/or citations are given for each medicinal used. Both patients improved during the
course of treatment; subjective signs and symptoms (especially fatigue) as well as liver enzyme levels demonstrated improvement.
PMID: 9395695 [PubMed - indexed for MEDLINE]
J Gastroenterol Hepatol 2002 Feb;17 Suppl:S146-54 Related Articles, Links
Management of viral hepatitis C.
Leung NW.
Prince of Wales Hospital and Chinese University of Hong Kong, Hong Kong. nancyleung@cuhk.edu.hk
The hepatitis C virus was first identified in 1989. It causes chronic hepatitis, cirrhosis and hepatocellular carcinoma.
Global anti-HCV prevalence is 1-3%. Contaminated blood product, dirty needles and instruments, and injection drug use are
the main parenteral routes of transmission. Cultural practices, such as acupuncture, tattoo, body piercing and scarring, also
play a role. Universal precaution is the mainstay for prevention before vaccine is developed. Therapy for chronic hepatitis
C (CHC) with interferon (IFN) is not satisfactory. Non-response and early relapse reduce sustained response (SR). In 1997,
National Institute of Health consensus recommended IFN therapy only for selected patients with compensated CHC, raised ALT
and moderate to severe histologic disease activity; 15-20% SR is expected. Major advances in CHC therapy is combination therapy.
Ribavirin in combination with IFN significantly increases SR to 30-40%. Even patients with high viral load, genotype 1, significant
fibrosis or cirrhosis respond better. EASL and APASL Consensus in 1999 recommended IFN-ribavirin combination as the first
line therapy. Recent data on pegylated IFN showed very encouraging results. Combined with ribavirin, 60% SR was achieved.
It benefits patients with severe bridging necrosis and also cirrhosis. However, 23-27% of patients receiving combination therapy
with either IFN type, experienced adverse events and required therapy discontinuation. Many important issues remained unsolved.
Therapy for children, the elderly, patients with comorbidity and extra-hepatic syndromes need to be addressed. Therapy is
too expensive and not affordable to the majority of patients in developing countries.
Publication Types: Review
Review, Tutorial
PMID: 12000600 [PubMed - indexed for MEDLINE]
Rinsho Byori 2000 Jan;48(1):5-13 Related Articles, Links
[Hepatitis C: epidemiology and therapy--with special reference to long-term prognosis after IFN therapy]
[Article in Japanese]
Fujiyama S, Tanaka M.
Third Department of Internal Medicine, Kumamoto University School of Medicine.
Blood transfusion or blood products are a important route for transmission of hepatitis C virus(HCV) infection. Routes
of infection other than blood transfusion are medical treatments including hemodialysis, exposure of hospital employees to
needles contaminated with blood, drug abusers, acupuncture, tattooing, certain types of sexual behavior and mother-to-infant
infection. The prevalence of anti-HCV antibodies in blood donors in Kumamoto Prefecture was 1.30%(1,704 of 131,376) between
February and October 1992 and 0.46%(622 of 132,847) between April 1998 and May 1999, respectively. Also, the prevalence of
anti-HCV was 22.9%(126 of 550) in the highly endemic area. The prevalence of HCV infection was evaluated in 548 patients undergoing
hemodialysis, and 216 members of the hospital dialysis staff. Of 548 hemodialysis patients, 166(30.3%) were positive and significantly
higher than those for either hospital staff members(2.3%; p < 0.01) or healthy blood donors(1.3%; p < 0.01). Patients
with a history of blood transfusion tended to have a higher positivity rate for anti-HCV than did the non-transfused group.
Positivity for anti-HCV was related to the duration fo hemodialysis. Although hemodialysis patients remain a high-risk group
for HCV infection, the prevalence of anti-HCV antibodies has decreased recently thanks to the use of erythropoietin for renal
anemia, the universal screening of blood donors for anti-HCV antibodies, and improvements in infection control measures for
this virus. To evaluate the effect of interferon(IFN) therapy on the incidence of hepatocellular carcinoma(HCC) or decompensated
liver cirrhosis, 490 patients with chronic hepatitis or liver cirrhosis type C who had undergone liver biopsy since 1987,
were followed periodically. Of these patients, 411 received IFN and 79 were untreated. The degree of liver fibrosis was assessed
from stage F0(no fibrosis) to stage F4(cirrhosis). Response to IFN was determined virologically and biochemically. HCC developed
in IFN-treated patients and in 17 untreated patients with stage F3 or F4 fibrosis. In multivariate analysis, IFN therapy was
associated with a reduced risk of HCC, especially among patients with sustained virological response(CR), among those with
persistently normal serum ALT levels, and among those with ALT levels less than two times the upper limit of normal(PR). Also,
the cumulative incidence of decompensated liver cirrhosis and cumulative survival in treated and untreated patients differed
significantly. None of the patients with CR or PR progressed to the decompensated state and all patients with CR or PR have
survived to date. In conclusion, IFN therapy significantly reduces the risk for HCC or decompensated cirrhotic stage, especially
among virological or biochemical responders.
PMID: 10756668 [PubMed - indexed for MEDLINE]
Hepatogastroenterology 2002 Mar-Apr;49(44):529-31 Related Articles, Links
Dietary iron restriction improves aminotransferase levels in chronic hepatitis C patients.
Iwasa M, Kaito M, Ikoma J, Kobayashi Y, Tanaka Y, Higuchi K, Takeuchi K, Iwata K, Watanabe S, Adachi Y.
Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu City, Mie 514-8507, Japan.
motoh@clin.medic.mie-u.ac.jp
BACKGROUND/AIMS: It is generally accepted that iron overload plays an important role in the pathogenesis of liver cell
injury in chronic hepatitis C. The present study was undertaken to evaluate whether low-iron diet improves liver function
tests in patients with chronic hepatitis C. METHODOLOGY: Seventeen patients with chronic hepatitis C (13 men and 4 women,
54 +/- 14 years old) that did not respond to, or were unsuitable for interferon therapy, were enrolled in this study. All
patients had been pretreated with ursodeoxycholic acid for more than 12 months before the beginning of the study. Dietary
iron intake was restricted to less than 7 mg/day, and the patients were followed up for 18 months. RESULTS: Mean daily iron
intakes, calculated from food records, were 5.9 and 6.4 mg after 6 and 12 months, respectively. The mean serum ferritin decreased
significantly from 362 ng/mL at entry to 179 ng/mL after 18 months. The serum unsaturated iron binding capacity level increased
significantly from 163 micrograms/dL at entry to 203 micrograms/dL after 18 months. The serum aspartate aminotransferase decreased
significantly from 62 IU/L at entry to 47 IU/L after 18 months, and serum alanine aminotransferase from 68 IU/L at entry to
53 IU/L after 18 months. Serum iron, hepatitis C virus-RNA titer and platelet count remained unchanged throughout the study.
CONCLUSIONS: These results suggest that iron-restricted diet may be an important therapeutic modality for improving liver
injury in patients with chronic hepatitis C.
PMID: 11995488 [PubMed - indexed for MEDLINE]
Br J Nutr 2000 Mar;83(3):235-9 Related Articles, Links
Beneficial influence of an indigenous low-iron diet on serum indicators of iron status in patients with chronic liver
disease.
Tandon N, Thakur V, Guptan RK, Sarin SK.
Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India.
The main Fe storage organ in the body is the liver. In patients with chronic liver disease, secondary Fe overload is common.
Phlebotomy, often used in the West to reduce Fe overload to improve the efficacy of interferon therapy, is not socially acceptable
in India. We assessed the efficacy of a low-Fe diet in reducing serum Fe levels. Nineteen patients with hepatitis B- and C-related
chronic liver disease, ten with normal (< 25 mumol/l) baseline serum Fe levels (group A) and nine with high (> 25 mumol/l)
serum Fe levels (group B) were included. All the subjects were advised to eat a low-Fe diet. The daily Fe intake was reduced
approximately 50% by consumption of the rice-based diet. Haemoglobin, serum Fe, transferrin saturation index (TSI), ferritin
and alanine transaminase (EC 2.6.1.2) levels were studied at 1 and 4 months. Dietary Fe intake and body weight were closely
monitored. All patients complied with the dietary regimen and at 4 months significant (P < 0.001) reductions from baseline
were seen in serum Fe (20 (SD 3) v. 12 (SD 4) mumol/l group A; 30 (SD 3) v. 19 (SD 7) mumol/l group B) and TSI (38 (SD 8)
v. 23 (SD 9)% group A; 53 (SD 15) v. 34 (SD 13)%, group B) in both the groups, albeit earlier in group B subjects. Serum ferritin
levels, however, reduced only in group A (112 (SD 62) v. 43 (SD 25) ng/ml, P < 0.05) and not in group B. Non-significant
reductions in haemoglobin levels were seen in both groups. Alanine transaminase levels reduced significantly (P < 0.05)
in both the groups (95 (SD 49) v. 44 (SD 25) IU/l, group A; 82 (SD 16) v. 51 (SD 14) IU/l group B). Thus, a low-Fe diet results
in significant reductions in serum Fe and TSI levels, irrespective of baseline Fe levels. This diet should be evaluated to
improve the efficacy of interferon therapy in patients with hepatitis B- and C-related chronic liver disease.
PMID: 10884711 [PubMed - indexed for MEDLINE]
Eur J Gastroenterol Hepatol 1995 Feb;7(2):151-4 Related Articles, Links
Effects of ursodeoxycholic acid on serum liver enzymes in patients with hepatitis C virus-related chronic liver disease.
Puoti C, Magrini A, Filippi T, Annovazzi G, Pannullo A.
Liver Unit, Marino General Hospital, Rome, Italy.
OBJECTIVE: To study the effect of ursodeoxycholic acid (UDCA) on serum liver enzyme levels [alanine aminotransferase (ALT)
and gamma-glutamyl transferase (GGT)] in 101 patients with hepatitis C virus-related chronic liver disease. METHODS: Forty-nine
patients were assigned to receive UDCA (450 mg/day) over a period of 6 months and 52 to receive no treatment. RESULTS: In
the UDCA group, serum ALT and GGT levels significantly improved. ALT values decreased from pre-treatment levels of 157.0 +/-
62.6 IU/l to 82.5 +/- 46.4 IU/l (P < 0.05), and GGT fell from 141.3 +/- 86.2 IU/l to 66.0 +/- 49.5 IU/l (P < 0.001).
No significant change occurred in the mean ALT and GGT levels in the control group. CONCLUSION: Although our encouraging preliminary
results must be validated by double-blind histological trials, UDCA may be an alternative treatment for patients who fail
to respond to interferon therapy.
Publication Types:
Clinical Trial
Controlled Clinical Trial
Randomized Controlled Trial
PMID: 7712308 [PubMed - indexed for MEDLINE]
Hepatology 1995 Feb;21(2):322-7 Related Articles, Links
Interferon and ursodeoxycholic acid combined therapy in the treatment of chronic viral C hepatitis: results from a controlled
randomized trial in 80 patients.
Boucher E, Jouanolle H, Andre P, Ruffault A, Guyader D, Moirand R, Turlin B, Jacquelinet C, Brissot P, Deugnier Y.
Clinique des Maladies du Foie, Hopital Pontchaillou, Rennes, France.
Because 70% to 75% of patients with chronic hepatitis C either do not respond to or relapse after interferon (IFN) therapy,
and because ursodeoxycholic acid (UDCA) has been shown to reduce aminotransferase levels in patients with chronic hepatitis,
we undertook a prospective controlled randomized trial of IFN (group I) versus IFN plus UDCA (group II) in 80 patients with
chronic hepatitis C. IFN was administered in both groups for 6 months (3 to 5 million units [MU] three times a week), and
in group II UDCA (10 mg/kg/d) was administered with IFN and then alone for 3 additional months. Response to therapy was defined
as the normalization of alanine transaminase (ALT) levels. The results showed that 6 months after cessation of IFN, 59% of
responders had relapsed in group I but only 27% had relapsed in group II (P = .03). There was no difference between the two
groups for the initial (month 6) and the late (months 15 and 18) response rates to IFN. There was no virological effect or
significant histological improvement attributable to the addition of UDCA to IFN treatment. In conclusion, the results of
this study show that the addition of UDCA to IFN therapy significantly prolongs the period for which serum ALT remain, within
the normal range after discontinuation of IFN. Further studies would be required to determine whether UDCA has any potential
for long-term amelioration of the histological severity of liver disease caused by hepatitis C virus (HCV) infection, and,
therefore, whether it could be advocated as an adjunct to antiviral therapy.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 7843700 [PubMed - indexed for MEDLINE]
Eur J Gastroenterol Hepatol 1999 Oct;11(10):1077-83 Related Articles, Links
Combined ursodeoxycholic acid and glycyrrhizin therapy for chronic hepatitis C virus infection: a randomized controlled
trial in 170 patients.
Tsubota A, Kumada H, Arase Y, Chayama K, Saitoh S, Ikeda K, Kobayashi M, Suzuki Y, Murashima N.
Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.
OBJECTIVE AND DESIGN: To assess the efficacy and safety of combination therapy using ursodeoxycholic acid with glycyrrhizin
for chronic hepatitis C virus infection, we conducted a prospective randomized controlled trial of glycyrrhizin (group G)
compared with glycyrrhizin plus ursodeoxycholic acid (group G+U) in 170 patients. METHODS: All patients had elevated serum
aminotransferase levels over 6 months before entry into the trial. Glycyrrhizin was administered to both groups for 24 weeks,
and in group G+U, ursodeoxycholic acid (600 mg/day) was administered orally as well. RESULTS: Serum aspartate transaminase
and alanine transaminase concentrations significantly decreased during treatment in both groups, but serum gamma-glutamyl
transpeptidase concentrations fell significantly only in group G+U. Concentrations of all three enzymes fell significantly
more in group G+U than in group G, and had normalized in more cases when the trial ended at 24 weeks. However, levels of HCV
viraemia did not change during the trial in either group. Multiple regression analysis linked only the treatment regimen,
not HCV-related factors or liver histology, to the degree of serum enzyme reduction. No adverse effects were noted in either
group. CONCLUSIONS: The combined therapy with ursodeoxycholic acid and glycyrrhizin is safe and effective in improving liver-specific
enzyme abnormalities, and may be an alternative to interferon in chronic hepatitis C virus infection, especially for interferon-resistant
or unstable patients.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 10524635 [PubMed - indexed for MEDLINE]
J Gastroenterol Hepatol 1996 Dec;11(12):1155-60 Related Articles, Links
Efficacy of ursodeoxycholic acid in combination with interferon-alpha in treating chronic hepatitis C: results of a long-term
follow-up trial.
Tanaka K, Kondo M, Sakaguchi T, Saito S, Arata S, Ikeda M, Kitamura T, Morimoto M, Sekihara H.
Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Ursodeoxycholic acid (UDCA) has recently been combined with interferon (IFN) in the treatment of individuals with chronic
hepatitis C. However, whether its addition results in a long-term favourable response to IFN remains unclear. A prospective
randomized trial of IFN alone versus IFN plus UDCA was therefore undertaken in 52 patients with chronic hepatitis C. All patients
received a 24 week course of IFN-alpha (6 x 10(6) U/day for 2 weeks and then three times a week for 22 weeks) and half also
received UDCA (600 mg/day) with IFN and then alone for 48 additional weeks. Normalization of serum alanine transaminase (ALT)
concentrations at 0, 24 and 48 weeks after cessation of IFN therapy was apparent in 77, 42 and 42% of patients in the IFN-alone
group and in 77, 54 and 42% of patients in the IFN plus UDCA group, respectively. There was no significant difference between
the two groups with regard to response rate to IFN and the addition of UDCA to IFN treatment had no significant effect on
hepatitis C virus (HCV) viraemia. During the follow-up period, 10 of 20 patients with normal serum ALT at the end of IFN treatment
relapsed in the IFN-alone group compared with 11 of 20 patients in the IFN plus UDCA group. Among these relapsed patients,
serum ALT concentration was significantly lower in the IFN plus UDCA group than in the IFN-alone group during the follow-up
period. Twenty-four weeks after cessation of IFN therapy, the percentage of patients with HCV-RNA in their serum who showed
a normalization of serum ALT concentrations was significantly higher in the IFN plus UDCA group than in the IFN-alone group
(44 vs 6%). Thus, although the addition of UDCA was not associated with a favourable long-term response to HCV viraemia, it
did reduce the risk and the severity of relapse following the cessation of IFN therapy.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 9034935 [PubMed - indexed for MEDLINE]
Hepatic Encephalopathy
(Liver caused brain inflammation and degeneration)
Long term alcohol use can result in fat entering the liver and scarring (cirrhosis). Over time, this may impede the
liver's functioning and/or provide the liver's blood with a direct route back into the blood stream (a shunt). In time, a
number of toxins (metabolic products, primarily ammonia) may find their way into the brain. These can cause swelling, which
can be worsened by other compounds (glutamine) that come in to bring them out. The resulting effects are termed Hepatic Encephalopathy
(HE). Since 2002, the definition for alcohol cirrhosis related disease has been updated to Hepatic Encephalopathy type C.
Current treatment for HE includes dietary restriction, but there is argument about whether protein restriction is advisable
or not. Non-absorbable sugars are given, but it is unclear how they work. Improving diet does seem to help in both the short
and long-term.
The long-term results of ignoring HE (failure, coma) are very serious, and if this diagnosis is possible, all necessary
precautions should be taken.
Rocz Akad Med Bialymst. 2002;47:186-93. Related Articles, Links
Early detection of hepatic encephalopathy by recording visual evoked potential (VEP).
Zamir D, Storch S, Kovach I, Storch R, Zamir C.
Department of Internal Medicine D, Barzilai Medical Center, Israel. zamir@barzi.health.gov.il
The visual evoked potential (VEP) record in response to a pattern stimulus is a non invasive and reliable method of detecting
central and peripheral nerve system abnormalities. VEP recording have been used in animals with fulminant hepatic failure,
and also in-patients with hepatic encephalopathy and acute severe hepatitis. Our aims were: a. to evaluate the potency of
PVEP in assessing hepatic encephalopathy. b. to find the rate of pathologic PVEP in patients with advanced liver cirrhosis.
VEP was recorded in 14 chronic liver cirrhotic patients (6 alcoholic, 6 HCV-related, 2 cryptogenic) and 14 controls. Patients
with any neurologic abnormalities were excluded from the study. All patients were subjected to the Mental State Score (MSS)
test, and venous blood ammonia was measured on the same day of VEP recording. In 10/14 (71%) patients some VEP recording abnormality
was detected. In the cirrhotic patients, P100 latency was significantly longer (P < 0.05) than in controls. Low amplitude
was observed in 8 patients compared to controls. Marked increase of N75 (3 patients) and marked increase of N145 (2 patients)
were observed. Mean blood ammonia and MSS score were normal in all patients. No correlation was found between both MSS score
and blood ammonia levels and the P100 delay. Five out of 10 patients with pathologic VEP developed hepatic encephalpathy during
a follow-up of one year, compared to one out of 4 patients with no pathology on VEP recording. VEP recording may be a valuable
tool in assessing patients with early hepatic encephalopathy and in predicting encephalopathy.
PMID: 12533959 [PubMed - indexed for MEDLINE]
Endocrine. 2003 Nov;22(2):143-50. Related Articles, Links
Chronic daily ethanol and withdrawal: 4. Long-term changes in plasma testosterone regulation, but no effect on GnRH gene
expression or plasma LH concentrations.
Rasmussen DD, Sarkar DK, Roberts JL, Gore AC.
VA Puget Sound Health Care System, S-116 Mental Illness Research, Education and Clinical Center, 1660 S. Columbian Way,
Seattle, WA, USA. drasmuss@u.washington.edu
Although ethanol has been repeatedly demonstrated to inhibit the hypothalamo-pituitary-testes axis by multiple mechanisms,
plasma testosterone levels can be normal in alcoholics who do not exhibit severely compromised liver function and even increased
in some abstinent alcoholics, suggesting that adaptive changes to chronic alcohol abuse may alter these regulatory mechanisms.
To address this variability, we have investigated the effects of chronic ethanol and withdrawal on rat testosterone regulation
using a well-characterized liquid diet model that we have previously demonstrated to (1) provide daily oral ethanol consumption
that produces behaviorally relevant plasma ethanol levels during the active (awake) stage of the photoperiod; (2) establish
physical dependence on ethanol; and (3) produce not only hypothalamo-pituitary-adrenal axis, but also behavioral (anxiety-like
behavior, response to novelty, sucrose preference) changes consistent with those of actively drinking and subsequently abstinent
alcoholics. The results demonstrate that chronic daily episodes of ethanol consumption and withdrawal by male Sprague-Dawley
rats decreased (p < 0.01) plasma testosterone levels late in the afternoon (by 70% relative to ad libitum-fed controls
and 63% relative to pair-fed controls), but not in the morning. During gradual cessation of daily ethanol consumption, morning
plasma testosterone levels increased, and this 90-115% (p < 0.05) increase was maintained for 3 d after complete cessation
of ethanol consumption. Three weeks after cessation of ethanol consumption, plasma testosterone levels were again increased
by approx 100% (p < 0.01). Plasma luteinizing hormone (LH) concentrations and anterior hypothalamus/preoptic area gonadotropin-releasing
hormone (GnRH) mRNA levels were not altered at any of these time points. Thus, chronic daily ethanol consumption and daily
withdrawal induced changes in circulating testosterone regulation that (a) were time of day dependent and (b) included adaptive
changes persisting long after consumption of ethanol ceased. Accordingly, resolution of changes in testosterone regulation
and their potential roles in alcohol abuse and relapse will require evaluating changes throughout the circadian cycle during,
shortly after, and long after active alcohol abuse.
PMID: 14665718 [PubMed - in process]
Alcohol Clin Exp Res. 2003 Apr;27(4):682-5. Related Articles, Links
Testosterone increases in men after a low dose of alcohol.
Sarkola T, Eriksson CJ.
Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland.
BACKGROUND: Heavy acute alcohol drinking decreases blood testosterone in men due to an effect on the testicular level.
An acute increase in blood testosterone levels after a low alcohol dose has, however, recently been reported in women. The
objective of this investigation was to study the effect of a low alcohol dose on testosterone in men and further elucidate
the mechanism behind the effect by using 4-methylpyrazole, an inhibitor of alcohol metabolism. METHODS: A double-blind placebo-controlled
interventional crossover trial in random order (n = 13). RESULTS: After intake of alcohol (0.5 g/kg, 10% w/v), an acute increase
in plasma testosterone (from 13.5 +/- 1.2 nmol/liter to 16.0 +/- 1.6 nmol/liter, mean +/- SEM; p < 0.05), a decrease in
androstenedione (from 5.1 +/- 0.4 nmol/liter to 4.0 +/- 0.3 nmol/liter; p < 0.05), and an increase in the testosterone:androstenedione
ratio (from 2.8 +/- 0.3 to 4.2 +/- 0.4; p < 0.01) were observed. The effects were not observed during pretreatment with
4-methylpyrazole (10-15 mg/kg orally), which inhibited the ethanol elimination rate by 37 +/- 3%. CONCLUSIONS: Alcohol intake
affects the androgen balance in men through an effect mediated by the alcohol-induced change in the redox state in the liver.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12711931 [PubMed - indexed for MEDLINE]
Alcohol Alcohol. 2003 Sep-Oct;38(5):400-6. Related Articles, Links
J Clin Endocrinol Metab. 2001 May;86(5):1981-5. Related Articles, Links
The role of the liver in the acute effect of alcohol on androgens in women.
Sarkola T, Adlercreutz H, Heinonen S, von Der Pahlen B, Eriksson CJ.
Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland.
The hypothalamic-pituitary-gonadal and -adrenal axes are regarded as the main sites of the actions of alcohol on steroids.
In the present study the effect of alcohol (0.4-0.5 g/kg, orally) on venous plasma and urinary androgens was investigated
in 21 premenopausal women using oral contraceptives as well as in 10 premenopausal nonusers. After intake of alcohol, an acute
elevation in plasma testosterone, a decline in androstenedione levels, and an elevation in the ratio of testosterone to androstenedione
were observed in both groups. The effects lasted throughout the period of ethanol elimination and were abolished during pretreatment
with 4-methylpyrazole (10-15 mg/kg, orally). The acute effects were higher in the group using oral contraceptives than in
the nonusers. The testosterone effect in plasma was reflected in the free testosterone fraction. A decline in urinary androsterone
and etiocholanolone levels, the principal catabolic products of androgens, was observed during alcohol intoxication. In conclusion,
the present acute effects on plasma and urinary steroid hormones seem to be explained by an inhibited catabolism mediated
by the alcohol-induced change in the redox state in the liver. Our results suggests that the liver should be included as a
major site in the acute endocrinological effects of alcohol on steroid hormones in women.
PMID: 11344195 [PubMed - indexed for MEDLINE]
L-carnitine alleviates alcohol-induced liver damage in rats: role of tumour necrosis factor-alpha.
Bykov I, Jarvelainen H, Lindros K.
Department of Mental Health and Alcohol Research, National Public Health Institute, POB 33, 00251 Helsinki, Finland.
AIMS: Excessive alcohol intake induces hepatic fatty infiltration, which has been suggested to sensitize the liver to
further damage. To test this hypothesis, L-carnitine, a constitutional lipotropic compound, was administered to rats chronically
treated with ethanol by liquid diet feeding for 10 weeks. RESULTS: Ethanol administration caused marked steatosis, mild inflammation
and elevated plasma alanine aminotransferase and tumour necrosis factor alpha (TNF-alpha) concentrations. Dietary supplementation
with L-carnitine significantly reduced all these parameters as well as the hepatic concentration of thiobarbituric acid reactive
substances, an indicator of lipid peroxidation products. Pretreatment with L-carnitine also significantly blunted ethanol-induced
stimulation of TNF-alpha release by isolated Kupffer cells. CONCLUSIONS: This study provides direct support for the notion
that steatosis sensitizes the liver to further damage and suggests an involvement of TNF-alpha in this process.
PMID: 12915513 [PubMed - indexed for MEDLINE]
Neuropsychobiology. 1999;39(3):144-50. Related Articles, Links
Lower serum zinc in relation to serum albumin and proinflammatory cytokines in detoxified alcohol-dependent patients without
apparent liver disease.
De Vos N, Song C, Lin A, Demedts P, Wauters A, Neels H, De Jongh R, Kenis G, Bosmans E, Altamura C, Maes M.
Clinical Research Center for Mental Health (CRC-MH), Antwerp, Belgium.
Recently, it was reported that there may be an activation of the inflammatory response system in detoxified alcohol-dependent
patients without apparent liver disease (AWLD). The aims of the present study were to examine serum zinc (Zn) concentrations,
total serum protein (TSP) and patterns obtained in the electrophoretically separated protein fractions in relation to serum
interleukin-6 (IL-6) and IL-8 concentrations in detoxified AWLD patients. Zn, TSP, SP electrophoresis, and serum IL-6 and
IL-8 concentrations were determined in detoxified AWLD patients and age-matched healthy volunteers. Serum Zn, TSP and the
serum concentrations of albumin (Alb) and the beta fraction were significantly lower in detoxified AWLD patients than in healthy
volunteers. The percentage of the alpha2 fraction was significantly higher in detoxified AWLD patients. Lower serum Zn in
detoxified AWLD patients was attributable to lowered serum Alb. Lower serum Alb was significantly and negatively correlated
to increased serum IL-8. The percentage of the alpha1 and alpha2 fractions were significantly and positively related to serum
IL-6 and IL-8. The results show that there is an in vivo activation of the inflammatory response system in detoxified AWLD
patients and that lower serum Zn may be causally related to lower serum Alb.
Publication Types:
Clinical Trial
PMID: 10087459 [PubMed - indexed for MEDLINE]
Psychopharmacology (Berl). 2003 Jul;168(3):280-92. Epub 2003 Apr 24. Related Articles, Links
Effects of repeated withdrawal episodes, nicotine dose, and duration of nicotine exposure on the severity and duration
of nicotine withdrawal in rats.
Skjei KL, Markou A.
Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037,
USA.
RATIONALE: The aversive aspects of nicotine withdrawal contribute to high relapse rates to tobacco smoking after cessation
attempts. OBJECTIVES: To investigate the influence of nicotine dose, duration of nicotine exposure, and withdrawal history
on the severity of nicotine withdrawal in rats, as assessed by brain stimulation reward thresholds and somatic signs of withdrawal.
METHODS: Repeated spontaneous and precipitated withdrawals were investigated through four successive removals of osmotic minipumps
delivering nicotine/saline, or with daily injections of the nicotinic receptor antagonist dihydro-beta-erythroidine during
chronic nicotine/saline exposure, respectively. The effects of dose and duration of exposure were investigated using minipumps
of varying duration delivering different nicotine doses. RESULTS: Increased duration of nicotine exposure: a). prolonged the
duration but did not alter the magnitude of withdrawal-associated threshold elevations; b). increased somatic signs early
during withdrawal. Increased total nicotine exposure (i.e. increased dose and exposure duration) increased the duration of
threshold elevations (no effect on magnitude) but had no effect on somatic signs. Neither repeated spontaneous nor repeated
precipitated withdrawals altered the magnitude of withdrawal significantly. CONCLUSIONS: Increases in total nicotine dose
resulted in increased severity of the affective aspects of withdrawal. Further, continuous drug exposure resulted in longer
lasting withdrawal than intermittent administration even when the total nicotine dose was the same. There was no correlation
between threshold elevations and somatic signs of withdrawal. In conclusion, the severity of nicotine withdrawal is mitigated
by characteristics of the drug exposure regimen such as drug dose, duration of exposure and whether exposure is continuous
or intermittent.
PMID: 12712232 [PubMed - indexed for MEDLINE]
Psychopharmacology (Berl). 2003 Jan;165(3):280-90. Epub 2002 Nov 14. Related Articles, Links
Oral caffeine maintenance potentiates the reinforcing and stimulant subjective effects of intravenous nicotine in cigarette
smokers.
Jones HE, Griffiths RR.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive,
Baltimore, MD 21224-6823, USA. hendreejones@yahoo.com
RATIONALE: Epidemiological, clinical and pre-clinical observations suggest that caffeine can potentiate the reinforcing
and discriminative effects of nicotine. OBJECTIVE: The present study examined whether chronic exposure to moderate doses of
caffeine affects the reinforcing and subjective effects of intravenously administered nicotine. METHODS: The effects of oral
caffeine maintenance on the subjective and physiological effects of intravenously administered nicotine and caffeine were
examined using double-blind methods in nine volunteers with current use of tobacco, caffeine, and cocaine. Each subject was
exposed to two chronic drug phases (200 mg/70 kg oral caffeine t.i.d. and placebo t.i.d.), each of at least 12 days duration.
Within each drug phase, the subject received intravenous injections of placebo, nicotine (1.0 and 2.0 mg/70 kg), and caffeine
(200 and 400 mg/70 kg) in mixed order. Physiological and subjective data were collected before and repeatedly after drug or
placebo injection. RESULTS: Both intravenous nicotine and caffeine produced significant increases in ratings of drug effect,
stimulated, rush, and bad effect, with only nicotine significantly increasing ratings of liking and good effect. Caffeine
maintenance significantly increased ratings of drug effect and stimulated after the high dose of nicotine, and significantly
decreased ratings of bad effect after the low dose of nicotine. Caffeine maintenance also significantly increased the identification
of the low dose of nicotine as a stimulant. A drug versus money measure of reinforcement showed that subjects were willing
to pay money to receive nicotine injections, but willing to forfeit money to avoid caffeine injections. Furthermore, subjects
were willing to pay significantly more money to receive the high dose of nicotine in the caffeine maintenance phase than in
the abstinence phase. Both intravenous nicotine and caffeine increased diastolic blood pressure and decreased skin temperature,
and nicotine also increased heart rate. These physiological effects of intravenous nicotine and caffeine as well as the subjective
effects of intravenous caffeine were not influenced by caffeine maintenance. CONCLUSIONS: The results extend recent clinical
and preclinical findings by showing that oral caffeine maintenance can potentiate the reinforcing and stimulant subjective
effects of nicotine.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 12434259 [PubMed - indexed for MEDLINE]
Trop Gastroenterol. 2003 Apr-Jun;24(2):59-62. Related Articles, Links
Nutrition in the management of hepatic encephalopathy.
Srivastava N, Singh N, Joshi YK.
Department of Food and Nutrition, MS University, Vadodara.
Nutritional factors play a major role both in the pathogenesis as well as management of hepatic encephalopathy (HE). Physicians
treating patients with chronic liver disease often restrict the intake of dietary protein to prevent a rise in blood ammonia
levels. The role of protein restriction in patients with chronic hepatic encephalopathy (CHE) has been questioned recently
as the efficacy of protein withdrawal in patients with CHE has never been subjected to a controlled trial. Evidence suggests
that protein intake plays only a limited role in precipitating encephalopathy. In fact, measures taken to suppress endogenous
protein breakdown are more effective than dietary restrictions in reducing the load of amino acids on the decompensated liver.
A protein intake of less than 40 g per day, as has been indicated, contributes to a negative nitrogen balance, which along
with increased endogenous protein breakdown, worsens encephalopathy. A positive nitrogen balance may have positive effects
on encephalopathy. Rather, depressed plasma branched-chain amino acid (BCAA) levels, implicated in the pathogenesis of HE,
also supervene in cirrhosis only when malnutrition is present as well. Therefore, the emphasis in the nutritional management
of patients with HE should not be on the reduction of protein intake. Instead, the goal should be to promote synthesis by
making available ample amounts of amino acids, while instituting other measures to reverse the ongoing catabolism. Different
protein sources have varying effects on HE and efforts should be made to identify the most tolerated protein source to prevent
malnutrition and maintain these patients on a long-term basis.
Publication Types:
Review
Review, Tutorial
PMID: 14603821 [PubMed - indexed for MEDLINE]
Aliment Pharmacol Ther. 2003 Aug 15;18(4):357-73. Related Articles, Links
Review article: Nutritional therapy in alcoholic liver disease.
Stickel F, Hoehn B, Schuppan D, Seitz HK.
Department of Medicine I, University of Erlangen-Nuremberg, Germany.
Chronic alcohol consumption may lead to primary and secondary malnutrition. In particular, protein energy malnutrition
not only aggravates alcoholic liver disease but also correlates with impaired liver function and increased mortality. Therefore,
in these patients, adequate nutritional support should be implemented in order to improve their prognosis. Clinical trials
addressing this issue have shown that nutritional therapy either enterally or parenterally improves various aspects of malnutrition,
and there is increasing evidence that it may also improve survival. Therefore, malnourished alcoholics should be administered
a diet rich in carbohydrate- and protein-derived calories preferentially via the oral or enteral route. Micronutrient deficiencies
typically encountered in alcoholics, such as for thiamine and folate, require specific supplementation. Patients with hepatic
encephalopathy may be treated with branched-chain amino acids in order to achieve a positive nitrogen balance. Fatty liver
represents the early stage of alcoholic liver disease, which is usually reversible with abstinence. Metadoxine appears to
improve fatty liver but confirmatory studies are necessary. S-adenosyl-L-methionine may be helpful for patients with severe
alcoholic liver damage, since various mechanisms of alcohol-related hepatotoxicity are counteracted with this essential methyl
group donor, while a recent large trial showed that the use of polyenylphosphatidylcholine is of limited efficacy.
Publication Types:
Review
Review, Tutorial
PMID: 12940921 [PubMed - indexed for MEDLINE]
Med Hypotheses. 2003 Aug;61(2):307-13. Related Articles, Links
Probiotics can treat hepatic encephalopathy.
Solga SF.
Johns Hopkins Hospital, Baltimore 21205, USA. solga@jhmi.edu
Hepatic encephalopathy (HE) is a common and dreaded complication of liver disease. The effects of HE can range from minimal
to life threatening. Even 'minimal HE' causes major dysfunction in many aspects of daily living. The exact pathogenesis of
HE remains unknown. However, the products of gut flora metabolism are universally recognized as critical. Present treatments
for HE include the cathartic agent lactulose and poorly absorbable antibiotics. While effective, these treatments incur numerous
side-effects and cost.Probiotics are viable bacteria given orally to improve health. Probiotics have multiple mechanisms of
action that could disrupt the pathogenesis of HE and may make them superior to conventional treatment.
Publication Types:
Review
Review, Tutorial
PMID: 12888324 [PubMed - indexed for MEDLINE]
Rev Esp Enferm Dig. 2003 Feb;95(2):135-42, 127-34. Related Articles, Links
Hepatic encephalopathy: nomenclature, pathogenesis and treatment.
[Article in English, Spanish]
Quero Guillen JC, Carmona Soria I, Garcia Montes JM, Jimenez Saenz M, Herrerias Gutierrez JM.
Servicio de Aparato Digestivo. Hospital Virgen Macarena. Sevilla. Spain. queroguillen@yahoo.es
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome in patients with liver failure and/or a portal-systemic bypass.
Since 2002 a new nomenclature of HE exists, that classifies HE in encephalopathy type A (associated with acute liver failure),
type B (associated with portal-systemic bypass), and type C (associated with liver cirrhosis). HE type A is characterized
by a rapid development to coma, cerebral edema, and a poor short-term prognosis. Therefore, these patients should be referred
to a liver transplantation center. Standard treatment of HE consists of non absorbable disaccharides, non absorbable antibiotics,
and a diet with an appropriate amount of proteins. In addition, the possibility of performing a liver transplantation should
be evaluated. In patients with intractable HE other alternative treatments adjunct to standard treatment, like zinc, sodium
benzoate, ornithine aspartate, branched chain amino acids, flumazenil, and bromocriptine should be considered.
PMID: 12760720 [PubMed - indexed for MEDLINE]
Metab Brain Dis. 2002 Dec;17(4):221-7. Related Articles, Links
Pathophysiology of hepatic encephalopathy: a new look at ammonia.
Butterworth RF.
Neuroscience Research Unit, CHUM (Hopital Saint-Luc), University of Montreal, 1058 St-Denis Street, Montreal, Quebec H2X
314, Canada. roger.butterworth@umontreal.ca
Results of neuropathologic, spectroscopic, and neurochemical studies continue to confirm a major role for ammonia in the
pathogenesis of the central nervous system complications of both acute and chronic liver failure. Damage to astrocytes characterized
by cell swelling (acute liver failure) or Alzheimer Type II astrocytosis (chronic liver failure) can be readily reproduced
by acute or chronic exposure of these cells in vitro to pathophysiologically relevant concentrations of ammonia. Furthermore,
exposure of the brain or cultured astrocytes to ammonia results in similar alterations in expression of genes coding for key
astrocytic proteins. Such proteins include the structural glial fibrillary acidic protein, glutamate transporters, and peripheral-type
(mitochondrial) benzodiazepine receptors. Brain-blood ammonia concentration ratios (normally of the order of 2) are increased
up to fourfold in liver failure and arterial blood ammonia concentrations are good predictors of cerebral herniation in patients
with acute liver failure. Studies using 1H magnetic resonance spectroscopy in patients with chronic liver failure reveal a
positive correlation between the severity of neuropsychiatric symptoms and brain concentrations of the brain ammonia-detoxification
product glutamine. Increased intracellular glutamine may be a contributory cause of brain edema in hyperammonemia. Positron
emission tomography studies using 13HN3 provide evidence of increased blood-brain ammonia transfer and brain ammonia utilization
rates in patients with chronic liver failure. In addition to the use of nonabsorbable disaccharides and antibiotics to reduce
gut ammonia production, new approaches to the treatment of hepatic encephalopathy by lowering of brain ammonia include the
use of L-ornithine-L-aspartate and mild hypothermia.
Publication Types:
Review
Review, Tutorial
PMID: 12602499 [PubMed - indexed for MEDLINE]
Wiad Lek. 2002;55(5-6):301-9. Related Articles, Links
[Therapeutic management of hepatic encephalopathy]
[Article in Polish]
Helewski KJ, Kowalczyk-Ziomek GI, Konecki JJ.
Katedra i Zaklad Histologii i Embriologii SAM, ul. Jordana 19, 41-808 Zabrze.
Therapeutic management in hepatic encephalopathy depends on its etiology as well as progression degree. Both in acute
and chronic encephalopathy one should tend to establish probable causes and try to eliminate them. Cutting down on proteins
in diet is one of the most important suggestions in chronic hepatic encephalopathy. In order to reduce intestinal production
of ammonia, non-absorbable disaccharides (lactulose), antibiotics (neomycin) and sodium benzoate are the most commonly used.
Branched chain amino acids administered orally or parenterally may be useful in improving patient's condition and restoring
the balance of blood amino acids. The GABA-benzodiazepine receptor theory led to application of its antagonists, such as flumazenil,
in the management of hepatic encephalopathy. However, providing a proper treatment is not easy due to unstable and often not
very characteristic course of hepatic encephalopathy. What is more, clinical trials of some drugs used in the treatment of
hepatic encephalopathy do not confirm their effectiveness.
Publication Types:
Review
Review, Tutorial
PMID: 12235697 [PubMed - indexed for MEDLINE]
Dig Liver Dis. 2001 Aug-Sep;33(6):492-500. Related Articles, Links
Vegetarian diets in hepatic encephalopathy: facts or fantasies?
Amodio P, Caregaro L, Patteno E, Marcon M, Del Piccolo F, Gatta A.
Dept Medicine V, Clinical Nutrition, University of Padua, Italy. piero.amodio@unipd.it
Diet treatment characterized by a reduction in or a selection of food proteins is currently suggested in hepatic encephalopathy.
This article is a review of the present knowledge about the characteristics and the rationale of vegetarian diets in cirrhotic
patients with overt or latent encephalopathy. In addition, evidence relating diet and encephalopathy and the nutritional features
and needs of cirrhotic patients is reported. Finally, the rationale of a diet based on vegetable and milk-derived proteins
that may overcome the limits and the possible adverse effects of a strict vegetarian diet is presented.
Publication Types:
Review
Review, Tutorial
PMID: 11572577 [PubMed - indexed for MEDLINE] Eur J Gastroenterol Hepatol. 2001 Sep;13(9):1067-72. Related Articles,
Links
Role of Helicobacter pylori infection and its eradication in patients with subclinical hepatic encephalopathy.
Miquel J, Barcena R, Boixeda D, Fernandez J, SanRoman AL, Martin-de-Argila C, Ramosa F.
Department of Gastroenterology, Hospital Ramon y Cajal, Alcala Medicine University, Ctra Colmenar K, 9100 Madrid, Spain.
AIMS: Helicobacter pylori infection in cirrhotic patients has been associated with episodes of hepatic encephalopathy
(HE), although conclusive data are still lacking. This prospective study has evaluated the prevalence of H. pylori infection
in 37 patients with advanced cirrhosis of the liver and subclinical hepatic encephalopathy (SHE), diagnosed by changes in
psychometric tests and/or electrophysiological tests, as well as the repercussion of H. pylori eradication on ammonaemia and
the evolution of this disorder. RESULTS: A positive result for H. pylori infection was obtained in 22/37 (59%) patients. Initial
fasting blood levels of ammonia were high in both groups. Infected and non-infected patients showed similar levels (62.05
mmol/l v. 62.5 mmol/l), which were lowered by the standard diet, although statistical significance was only reached in the
infected patient group (53.05 +/- 26 mmol/l; P < 0.05). Infection was eradicated in 19 patients, but no reduction of blood
levels of ammonia was observed after H. pylori eradication among infected patients (52.37 +/- 29 mmol/l). No change has been
found in either group after the administration of diet or antimicrobials with regard to psychometric and/or electrophysiological
tests. CONCLUSIONS: H. pylori infection does not contribute significantly to high blood levels of ammonia in patients with
advanced cirrhosis and SHE. Likewise, H. pylori eradication does not induce any improvement in the psychometric and/or electrophysiological
tests used to define SHE.
PMID: 11564957 [PubMed - indexed for MEDLINE]
Br J Nutr. 2001 Mar;85 Suppl 1:S23-30. Related Articles, Links
Beneficial health effects of low-digestible carbohydrate consumption.
Scheppach W, Luehrs H, Menzel T.
Department of Medicine, University of Wuerzburg, Germany. w.scheppach@medizin.uni-wuerzburg.de
Low-digestible carbohydrates represent a class of enzyme-resistant saccharides that have specific effects on the human
gastrointestinal tract. in the small bowel, they affect nutrient digestion and absorption, glucose and lipid metabolism and
protect against known risk factors of cardiovascular disease. In the colon they are mainly degraded by anaerobic bacteria
in a process called fermentation. As a consequence, faecal nitrogen excretion is enhanced, which is used clinically to prevent
or treat hepatic encephalopathy. Low-digestible carbohydrates are trophic to the epithelia of the ileum and colon, which helps
to avoid bacterial translocation. Short-chain fatty acids are important fermentation products and are evaluated as new therapeutics
in acute colitis. They are considered in the primary prevention of colorectal cancer. The bifidogenic effect of fructo-oligosaccharides
merits further attention, Unfermented carbohydrates increase faecal bulk and play a role in the treatment of chronic functional
constipation, symptomatic diverticulosis and, possibly, the irritable bowel syndrome. In conclusion, low-digestible carbohydrates
may play a role in the maintenance of human digestive health. However, the strength of evidence differs between disease entities.
Publication Types:
Review
Review, Tutorial
PMID: 11321025 [PubMed - indexed for MEDLINE]
Postgrad Med. 2001 Feb;109(2):52-4, 57-60, 63-5 passim. Related Articles, Links
Hepatic encephalopathy. Metabolic consequence of cirrhosis often is reversible.
Abou-Assi S, Vlahcevic ZR.
Division of Gastroenterology, McGuire Veterans Affairs Medical Center and Virginia Commonwealth University School of Medicine,
1201 Broad Rock Rd, Richmond, VA 23249, USA. sabouassi@hotmail.com
Hepatic encephalopathy is a well-recognized clinical complication of chronic liver disease. About 30% of patients with
cirrhosis die in hepatic coma. Hepatic encephalopathy can occur in patients with fulminant liver disease without evidence
of portal-systemic shunting. These patients have increased intracranial pressure and brain edema with a deleterious clinical
course and poor prognosis unless liver transplantation is available. The pathogenesis of portal-systemic hepatic encephalopathy
probably is multifactorial, although the predominant causative agent appears to be ammonia. The molecular basis of neurotoxicity
of ammonia or other agents implicated in the condition is poorly understood. Therapy includes timely recognition and correction
of precipitating factors. Once the condition is manifested, standard therapy is acute administration of lactulose, a disaccharide
that is undigested in the small intestine. Its beneficial action is not fully understood. The use of oral antibiotics and
BCAAs is of some benefit in patients who do not respond to lactulose. Limitation of protein in the diet may be useful for
short periods but is not recommended for long-term use because of potential worsening of already poor nutrition. Several experimental
therapies based on potential pathogenetic mechanisms have not resulted in improved outcomes over standard therapy with lactulose.
However, future research will likely focus on the correction of alterations in neurotransmission. It is hoped that newer therapies
will provide protection from the putative neurotoxins that cause secondary defects in neurotransmission.
Publication Types:
Review
Review, Tutorial
PMID: 11272694 [PubMed - indexed for MEDLINE]
J Gastroenterol Hepatol. 2000 Dec;15(12):1436-41. Related Articles, Links
A balanced 5:1 carbohydrate:protein diet: a new method for supplementing protein to patients with chronic liver disease.
Ilan Y, Sobol T, Sasson O, Ashur Y, Berry EM.
Liver Unit, Department of Medicine, Hadassah Hebrew-University Medical School, Jerusalem, Israel. ilan@hadassah.org.il
BACKGROUND AND AIMS: Protein malnutrition in patients with chronic liver disease contributes to bone and muscle weakness
and compromises immune function and survival. In contrast, high-protein diets may induce or exacerbate hepatic encephalopathy.
The aim of the present study was to test whether increased amounts of protein, balanced by dietary carbohydrate in a 1:5 ratio,
may be given to chronic liver disease patients in order to minimize postprandial increases in plasma amino acid (AA) concentrations.
METHODS: Eight patients with chronic liver disease were studied. Each received, in a randomized order, three different diets
of 2510 kJ of either high protein (37:50:28, carbohydrate:protein:fat), high carbohydrate (126:10:6) or a balanced 5:1 carbohydrate:protein
diet (105:21:11). All patients were followed for plasma AA, glucose and insulin levels, as well as for cognitive and behavioral
changes. RESULTS: Following the high protein diet, AA concentrations were significantly increased. In contrast, after the
balanced diet, AA levels were practically constant enabled. All diets was well tolerated and no cognitive or behavioral changes
appeared. CONCLUSION: The administration of a balanced 5:1 carbohydrate:protein diet may enable patients with chronic liver
disease to tolerate increased amounts of dietary protein, without altering plasma amino acid concentrations.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 11197057 [PubMed - indexed for MEDLINE]
Med Sci Monit. 2000 Nov-Dec;6(6):1223-6. Related Articles, Links
Influence of the metabolic complications of liver cirrhosis on dietary intake.
Tozun N.
Department of Gastroenterology, Marmara Medical University, Istanbul, Turkey.
The role of the nutrition is discussed in relation to chronic liver disease. An outline of the general principles involved
in regulating nutrition in patients with advanced liver disease is given followed by an evaluation of the effects of malnutrition
on the outcome of the disease. Major problems faced over the course of advanced liver disease are carbohydrate intolerance,
sodium and fluid retention which may progress to hepatorenal syndrome, and hepatic encephalopathy. Interest on diet regulation
in such cases has been recently reemphasized in multicenter studies particularly in the liver transplant setting and alcoholic
liver disease. Controversies exist regarding albumin infusion after paracenthesis, low protein diet in hepatic encephalopathy
and water restriction before sodium. The effect of nutrition on the outcome of liver disease and survival is not well established.
However patients with better nutritional state do much better after transplant.
Publication Types:
Review
Review, Tutorial
PMID: 11208483 [PubMed - indexed for MEDLINE]
Nutrition. 1999 Apr;15(4):284-8. Related Articles, Links
Low plasma levels of docosahexaenoic acid in patients with liver cirrhosis and its correction with a polyunsaturated fatty
acid-enriched soft oil capsule.
Watanabe A, Saito S, Tsuchida T, Higuchi K, Okita M.
3rd Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Plasma levels of docosahexaenoic acid (DHA, C22:6 omega 3) were found to be decreased in 11 patients with alcoholic and
non-alcoholic liver cirrhosis depending on the severity of liver damage. In this reduction, we found impaired metabolism of
omega-3 long-chain polyunsaturated fatty acids in the cirrhotic liver and poor dietary intake of DHA to involved in the reduction
of DHA plasma levels. The deficiency of this fatty acid, which is concentrated in the nervous tissues, may be related to the
impaired neural function observed in hepatic encephalopathy of these patients. Oral DHA supplementation was supplied in the
form of a polyunsaturated fatty acid-enriched soft oil capsule (omega 3/omega 6 ratio = 0.91, and P/S ratio = 1.87). Twelve
capsules per day (containing 408 mg DHA, which corresponds to one-fourth of the DHA content in a normal daily diet) improved
the DHA contents in the plasma phospholipid fractions of 5 alcoholic patients with low DHA levels.
PMID: 10319360 [PubMed - indexed for MEDLINE]
Hepatology. 1994 Jan;19(1):67-71. Related Articles, Links
Gastrointestinal transit in cirrhotic patients: effect of hepatic encephalopathy and its treatment.
Van Thiel DH, Fagiuoli S, Wright HI, Chien MC, Gavaler JS.
Oklahoma Transplantation Institute, Baptist Medical Center of Oklahoma, Oklahoma City 73112.
Chronic hepatic encephalopathy is highly responsive to changes in diet, to antibiotic therapy and to ingestion of nondigestible
disaccharides. The precise pathophysiology of chronic hepatic encephalopathy in individual cases is highly variable, although
ammonia toxicity and production of neurotransmitterlike substances in the gut have been proposed to contribute to the overall
syndrome of chronic hepatic encephalopathy. The support for this hypothesis is based on the empiric observation that reduction
in protein intake, a catharsis or both are effective treatments for chronic hepatic encephalopathy. This study was performed
to evaluate the effect of mild subclinical and low-grade (grade 0 to 1) chronic hepatic encephalopathy on gastric emptying
and oral-cecal transit times. Thirty patients were studied. Ten had no evidence of chronic hepatic encephalopathy, as determined
with a battery of neuropsychiatric studies (group 1); 10 had subclinical hepatic encephalopathy, as judged on the basis of
abnormal neuropsychiatric test performance but normal neurological examination (group 2); and 10 had grade 1 hepatic encephalopathy.
Each underwent a liquid gastric emptying study and a lactulose oral-cecal transit time study. No significant differences between
groups were evident in the results of the gastric emptying studies. In contrast, the time required for a lactulose load to
reach the cecum was significantly greater in the patients with hepatic encephalopathy (p < 0.01) and increased as a function
of the hepatic encephalopathy grade.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 8276369 [PubMed - indexed for MEDLINE]
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