[Effects of supplementation with the antioxidant flavonoid, silymarin, in chronic hepatitis C patients treated with peg-interferon + ribavirin. A placebo-controlled double blind study]. / Az antioxidáns flavonoid silymarin szupplementációja hatásának placebokontrollos vizsgálata PEG-IFN + ribavirin antivirális kezelésben részesülô krónikus C-hepatitises betegekben.

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.

[Immunology of HCV infection: the causes of impaired cellular immune response and the effect of antiviral treatment]. / A hepatitis C-vírus-infekció immunológiája: az elégtelen celluláris immunválasz okai es az antivirális kezelés hatásai.

BACKGROUND: The outcome of HCV infection and the response to antiviral treatment depend on both viral and host factors. Host immune response contributes not only to viral control, clinical recovery and protective immunity, but also to chronic hepatitis and liver cirrhosis. Establishing immunological status and identifying pretreatment immunological factors associated with better response to therapy might be of importance in the understanding of the successful immune response and in the future of combination therapy to HCV infection. AIMS: The authors delivered a review on the immunology of HCV infection and characterized the cause of impaired cellular immune response in chronic HCV infection. Natural killer (NK) cell activity, perforin and the inhibitory CD81 HCV co-receptor expression, and Th1/Th2 cytokine production of the monocytes and lymphocytes have been investigated. PATIENTS AND METHODS: 42 patients with chronic hepatitis C, out of them 25 being on interferon (PEG-IFN) + ribavirin (RBV) therapy, 12 sustained virological responders, 26 HCV carriers with normal transaminase values and 22 healthy controls were studied. NK cell activity, perforin and CD81 expression, the IFNgamma, TNFalpha, IL-2 (Th1) and IL-4, IL-6, IL-10 (Th2) production of LPS stimulated monocytes and PMA + ionomycine stimulated lymphocytes were measured by flow-cytometry. RESULTS: In patients with chronic hepatitis C we demonstrated decreased NK cell activity associated with increased CD81 expression. The perforin expression of lymphocytes was also impaired in HCV patients. The pretreatment capacity of the macrophages to produce TNFalpha was predictive for sustained virological response. This increased TNFalpha production of the monocytes counteracted the observed impaired Th1 type cytokine production of the lymphocytes. IL-10 and IL-4 production showed positive correlation with HCV RNA levels, and negative correlation with histological activity index was noted. PEG-IFN + RBV treatment increased NK activity, perforin expression, Th1 type cytokine production of thr lymphocytes and downregulated CD81 expression inducing effective cellular immune response against HCV. The author's results provide further data to understand the causes of impaired cellular immune response in chronic HCV hepatitis and may be useful in the developement of immunotherapy as an adjunctive treatment to cure patients with chronic hepatitis C.