Danazol improves thrombocytopenia in HCV patients treated with peginterferon and ribavirin.

BACKGROUND: Thrombocytopenia is a common hematologic disorder observed in patients with chronic hepatitis C virus (HCV) infection. Combined peginterferon (PEG-INF) and ribavirin treatment may exacerbate thrombocytopenia in patients with HCV. OBJECTIVE: The aim of this pilot clinical trial was to assess the efficacy, tolerability and safety of Danazol in thrombocytopenia associated with PEG-INF and ribavirin treatment in patients with HCV. MATERIAL AND METHODS: We included patients whose platelets were < 90,000/mm³ and who were undergoing antiviral treatment. Danazol (300-600 mg/day) was administered during and until the end of antiviral therapy [7.6 months (2 to 11 months)]. The monitoring was performed through platelet analysis and liver function tests. A viral load test was done at the beginning and end of treatment. Fortynine patients receiving a combined therapy of PEG-INF, ribavirin and Danazol increased their platelet levels to 121,081/mm³ (46,000-216,000/mm³); 10.6% of patients gained > 100,000 platelets/mm³, and 71% of patients maintained their initial platelet levels. Sustained viral response (SVR) was achieved in 63% of patients. SVR rates were high in patients with genotype non 1 (78.7%) and decreased in patients with genotype 1 (60.1%). The increase in platelet levels was associated to an increase in fibrinogen levels and a decrease in the activity of ALT. By contrast, patients without SVR presented a delayed response to increased platelet levels and showed no significant improvement in liver function when they received Danazol. CONCLUSION: Danazol can be used along with PEG-INF and ribavirin to treat thrombocytopenia in patients with HCV.

Combined therapy with danazol, pegilated interferon, and ribavirin improves thrombocytopenia and liver injury in rats with fibrosis.

The aim of this study was to investigate the effects of combinations of pegilated-interferon (PEG-IFN), ribavirin, and danazol on thrombocytopenia and liver injury in rats with fibrosis. Male adult Wistar rats were treated with either mineral oil, danazol (0.83 mg/kg per day), PEG-interferon alpha-2a (PEG-IFN, 0.3 microg/ week) + ribavirin (12 mg/kg per day), PEG-IFN + ribavirin + danazol, CCl(4) (4 g/kg for eight weeks), CCl(4) + PEG-IFN + ribavirin, or CCl(4) + PEG-IFN + ribavirin+ danazol. The following assays were conducted: hematology, clinical chemistry, liver function, liver fibrosis, lymphocyte cytokine mRNA expression, and bone-marrow DNA content. Platelet counts were low in sham-treated animals and animals treated with PEG- IFN + ribavirin (30% and 25% respectively; P < 0.05). PEG-IFN + ribavirin + danazol reduced platelet counts of fibrotic animals by only 9% (P < 0.05). PEG- IFN + ribavirin reduced hepatic collagen content by 50%, whereas danazol + PEG-IFN + ribavirin reduced hepatic collagen content by 60% (P < 0.05). PEG-IFN + ribavirin reduced the total bilirubin concentration by 27%, alanine amino transferase (ALT) activity by 75% and gamma-glutamyl transpeptidase (gamma-GTP) activity by 74% (P < 0.05). In contrast, danazol + PEG-IFN + ribavirin reduced total bilirubin levels by 61%, alkaline phosphatase activity by 45%, ALT activity by 76%, and gamma-GTP activity by 74% (P < 0.05). The only treatment that increased interleukin 10 (IL-10) mRNA in fibrotic rats was PEG-IFN + ribavirin. However, danazol + PEG-IFN + ribavirin reduced the expression of IL-6, IL-10, tumor necrosis factor alpha and transforming growth factor ss. Bone-marrow DNA content was not altered by any treatment. In conclusion, PEG-IFN + ribavirin + danazol could be a new therapeutic option for patients with liver injury, fibrosis, and thrombocytopenia.