[Effects of supplementation with the antioxidant flavonoid, silymarin, in chronic hepatitis C patients treated with peg-interferon + ribavirin. A placebo-controlled double blind study].

UNLABELLED: Since oxidative stress may play a pathogenetic role in chronic hepatitis C, and sustained virological response to antiviral therapy is limited in HCV1 genotype infection, a double blind study was performed in HCV1 patients treated with pegylated interferon + ribavirin, to assess the efficacy of supplementation with the antioxidant flavonoid silymarin. PATIENTS AND METHODS: Thirty-two naive HCV1 positive patients with biopsy proven chronic hepatitis C, to be treated with pegylated interferon + ribavirin, have been randomized: group A): 16 patients have been given the antiviral therapy for 6-12 months plus placebo for the first 3 months; group B): 16 patients have been treated with pegylated interferon + ribavirin for 6-12 months plus silymarin, 2 x 166 mg/day, was given for 3 months. Serum alanine aminotransferase and HCV-RNA levels as well as parameters of oxidative stress such as plasma or red blood cell hemolysate, malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase and myeloperoxidase were determined after 0, 1, 3, 6 and 12 months during the treatment. Sustained virological response as undetectable serum HCV RNA was evaluated 24 weeks after the end of therapy.
RESULTS: In the silymarin group, a more rapid decrease in the malondialdehyde level as well as a marked decrease in superoxide dismutase and an increase in myeloperoxidase activity after month 12 were found, alanine aminotransferase normalized in 6/16 (vs control 9/16) cases, and sustained virological response occurred in 3/16 (vs 7/16) patients. DISCUSSION/
CONCLUSION: Although silymarin supportation to antiviral therapy improved oxidative stress, it was able to affect favourably neither the alanine aminotransferase nor the sustained virological response. These contradictory findings may be related to randomization bias as patients in study group B had more negative predictors of response: they were older with higher fibrosis score and even with more severe pretreatment baseline oxidative stress. Regarding the recently published in vitro experiments with silybinin on HCV replication as well as the newest convincing clinical observations, we do suggest further studies with more than three times higher doses of silymarin in controlled trials to assess the value of this supplementation in antivirally treated HCV patients.

RCT Entities:   Population Interventions Outcomes