Effect of Peg‐Interferon, Ribavirin and Danazol on experimental fibrosis induced in rats

The current standard therapy of patients with chronic hepatitis C is the combination of peg‐interferon (IFN)‐α and ribavirin.However, it is well known that interferon in combination with ribavirin treatment may exacerbate the neutropenia and thrombocytopenia in those patients. Danazol therapy seems to be a useful and well‐tolerated treatment for refractory immune thrombocytopenic associated with several autoimmune diseases. The aim of this work was to investigate whether the simultaneous administration of peg‐interferon, ribavirin and danazol mofify the liver fibrosis. Male Wistar were included in: Control; Danazol (0.166mg/day); IFN (1.2μg/week) + Ribavirina (1 mg/day); IFN + Rib + Dan; CCl 4 (0.4 g/kg/ 8 weeks); CCl 4 + IFN + Rib; CCl 4 + IFN + Rib + Dan. At the end of treatment we analyzed liver function and morphology, collagen content, and the mRNA for TGF‐beta1, TNF‐alpha, PDGF e interleukins (1, 6 and 10). Our results showed that the combined treatment with peg‐interferon, ribavirin and danazol improved the liver function and architecture. It was reduced the total amount of collagen which correlated with the collagen bands in liver tissue. The treatment with peg‐interferon, ribavirin and danazol induce a change in the patron of expression of pro‐imflamatory and anti‐inflamatory cytokines. Therefore the combine treatment with treatment with peg‐interferon, ribavirin and danazol appear to be a new terapeutic option in those patients with chronic hepatitis C virus infection.