Although there are many reports of the use of herbals for the treatment of chronic liver diseases, most treatment trials have suffered from poor scientific design, uncertainty of the required dosage of herbals, and an insufficient number of study participants. A recent review of complementary and alternative medications (CAM) to treat liver diseases focused on the classification, epidemiology, and the philosophy of CAM and reviewed the criteria needed to conduct a scientifically valid research study focusing on herbal products.
There has been skepticism regarding the evidence that silymarin has a direct impact on the hepatitis C virus (HCV)—some studies suggest that it does, but most studies are unable to confirm these reports. However, at least two articles in major journals have suggested that silymarin or its congeners may inhibit HCV. In one report, investigators found that a standardized silymarin extract inhibited tumor necrosis factor -alpha in anti-CD3–stimulated human peripheral blood mononuclear cells and nuclear factor-kappa B-dependent transcription in human hepatoma Huh-7 cells. Silymarin also displayed prophylactic and therapeutic effects against HCV infection and when combined with interferon-alpha, was more inhibitory of HCV replication than was interferon alone. This indicates that silymarin has anti-inflammatory and antiviral effects in patients with chronic hepatitis C.
In a case series /phase I study, patients with HCV were treated with intravenous silibinin with and without PEG-interferon and ribavirin. In the case series, 16 HCV nonresponder patients were administered intravenous silibinin in a dose of 10 mg/kg/day for 7 days. Subjects then began treatment with oral silibinin in combination with PEG-interferon and ribavirin for 12 weeks. At the end of the study period, all patients were positive for HCV RNA, but 5 of 13 completed patients had reductions in HCV RNA. Significance was not reported. In the same study, the authors presented results of a phase I study in which 20 patients were administered 5 mg/kg, 10 mg/kg, 15 mg/kg, or 20 mg/kg of silibinin for 14 days in combination with PEG-interferon and ribavirin (initiated on day 8). A significant drop in HCV RNA was observed on day 7 in patients administered the 10 mg/kg, 15 mg/kg, and 20 mg/kg doses of silybinin. Further declines were observed in HCV RNA with administration of PEG-interferon and ribavirin. Except for mild gastroenteritis, intravenous silibinin monotherapy was well tolerated.
In patients with chronic liver disease, a randomized, placebo-controlled study found normalization of serum AST, ALT, and bilirubin levels after 1 month of treatment with silymarin (140 mg 3 times a day) in comparison to treatment with a placebo. In one of the largest observational studies involving 2,637 patients with chronic liver disease, 8-week treatment with 560 mg/day of silymarin resulted in reductions of serum AST, ALT, and gamma-glutamyltranspeptidase ([GGT], a marker of bile duct disease) and a decrease in the frequency of palpable hepatomegaly.
Another published report describes the use of silybinin as the only effective antidote in patients with liver damage from Amanita phalloides (Fr.) Link poisoning. Patients were administered doses of 35 to 55 mg/kg body weight, with no reports of adverse events. A recent retrospective review of the treatment for Amanita phalloides poisoning suggests that silymarin continues to be a promising drug in the treatment of this rare mushroom poisoning. The beneficial effect of silymarin on liver histology suggests it has a role in the prevention of hepatitis and/or hepatocellular carcinoma; however, no clinical trials in humans have investigated these uses of silymarin.