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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(e.g. solvents) or iatrogenic (e.g. antispychotic or tacrine) liver diseases, which are mostly outdated and underpowered,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
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