PEGYLATED-INTERFERON AND RIBAVIRIN THERAPY OF HCV-RELATED TYPE II MIXED CRYOGLOBULINEMIA

Background. Mixed Cryoglobulinemia (MC) is the most frequent extrahepatic disease in patients affected by chronic hepatitis C virus (HCV) infection. It has been supposed that the association of pegylated-interferon (peg-IFN) alpha-2A and ribavirin (RBV) could represent a rational and effective therapy for HCV-related MC with detectable HCV RNA, not only in patients with hepatic disease [Chronic Hepatitis (CH), Child-Pugh Class A Hepatic Cirrhosis (HC)] but also without clinical, biochemical and histological signs of hepatic involvement. Aim. To evaluate safety and efficacy of peg-IFN alpha-2A in combination with RBV for treatment of HCV-related MC with detectable HCV RNA, in patients with and without hepatic disease. Methods. 235 patients affected by chronic HCV infection: 175 with CH, 38 with Child-Pugh Class A HC and 22 without hepatic disease. 24/235 patients affected by HCV-related type II MC: 16 with chronic liver disease (14 with CH, 2 with Child-Pugh Class A HC) and 8 without hepatic disease. All 24 patients affected by HCV-related type II MC, previously untreated, underwent treatment with standard dose of peg-IFN alpha-2A 180 mcg once weekly and weight based RBV (WBV) 1000 1200 mg/day. Results. At 12 weeks, 4/16 (25%) patients with hepatic disease (2 with CH and 2 with Child-Pugh Class A HC) were non-responders to therapy and stopped it. Twenty remaining patients (12 with CH and 8 without hepatic disease) early virological responders (EVR) continued therapy until to 48 weeks. At the end of therapy, we observed a strict association between the eradication of HCV and a complete clinical response (disappearance of cutaneous manifestations of cryoglobulinemic vasculitis) with a complete virological and clinical response in 12/16 (75%) and 8/8 (100%) patients with and without hepatic disease, respectively. Some patients (4 with hepatic disease and 1 without hepatic disease) relapsed both virologically and clinically a few weeks after the end of therapy. At the end of follow-up (72 weeks), in the first group 8/16 (50%) patients achieved a complete clinical response and sustained virological response (SVR), 4/16 (25%) non-responders and 4/16 (25%) relapsers, while in the second group 7/8 (87.5%) patients achieved a complete clinical response and SVR and 1/8 (12.5%) relapsers. Therefore, we observed a higher rate of complete clinical response and SVR (87.5% vs 50%) in patients without hepatic disease compared with patients with hepatic disease (p<0.01). Conclusions. peg-IFN alpha-2A in combination with RBV seems safe and useful for the treatment of HCV-related type II MC not only in patients with but also without hepatic disease. Moreover, in our study seems that the antiviral therapy is more efficacy in patients affected by HCV-related type II MC without hepatic involvement than in those with hepatic disease.