Biomedical subjects
Publications and source records attributed to Damien Sene.
Hepatitis C virus (HCV) is the leading cause of chronic liver disease in industrialized countries. HCV also causes a variety of extrahepatic disorders, of which systemic vasculitis, of the cryoglobulin or polyarteritis nodosa type, is the most severe. This article reviews the main diagnostic, pathophysiologic and therapeutic aspects of HCV-induced systemic vasculitis.
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OBJECTIVE: Type II mixed cryoglobulinemia (MC) is a systemic vasculitis usually associated with hepatitis C virus (HCV), which may involve the skin, kidneys, and nervous system. Molecular evidence of antigen-driven B cell proliferation is definitively provided in HCV-associated type II MC, and HCV appears to be the key trigger. The present trial was established to investigate the efficacy of therapy with PEGylated interferon alfa-2b (PEG-IFN alfa-2b) plus ribavirin in patients with HCV-related MC vasculitis. METHODS: Nine consecutive patients with HCV-related MC received PEG-IFN alfa-2b (1.5 microg/kg/week) subcutaneously plus oral ribavirin (800-1,200 mg/day) for at least 6 months. The response to treatment was analyzed by comparing clinical, immunologic, and virologic parameters at the initial evaluation with those observed during followup. RESULTS: The mean +/- SD duration of therapy with PEG-IFN alfa-2b plus ribavirin was 13.5 +/- 2.8 months. After a mean period of 18.6 months following discontinuation of treatment, all 9 patients are alive. Seven patients (78%) had a sustained virologic response and were complete clinical responders. Serum cryoglobulin disappeared in 5 of 9 patients (56%), and complement levels normalized in 80% of the patients. One patient had a partial virologic response with a complete clinical response. In another patient, a clinical relapse of MC vasculitis occurred in association with the reappearance of HCV RNA. Treatment was well tolerated, and no patient had side effects for which discontinuation of therapy was required. CONCLUSION: Treatment with PEG-IFN alfa-2b plus ribavirin can achieve a complete clinical response in most patients with HCV-related MC vasculitis. Complete clinical response correlates with the eradication of HCV and requires a shorter treatment period than that previously reported for IFNalpha plus ribavirin.
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OBJECTIVE: To describe epidemiological, clinical, and immunological characteristics and the longterm course of persistent mixed cryoglobulinemia (MC) in patients infected with hepatitis C virus (HCV). METHODS: Retrospective study of HCV infected patients (HCV RNA positive) who had persistent positive MC, with 2 immunochemical typings of MC carried out after 24-month minimum interval. RESULTS: In total, 125 patients were studied, aged 52 +/- 13 years at diagnosis of MC, with duration of HCV infection of 18 +/- 10 years. At entry, 60 patients had type II MC, 53 patients had type III, and 12 patients had the oligoclonal type. At the second immunochemical typing, after a mean interval of 45 +/- 20 months, MC was type II in 72 patients, type III in 39 patients, and the oligoclonal type in 14 patients. The proportion of cases of MC with the same immunochemical type was higher among patients with type II (78%) than type III (59%) or oligoclonal MC (17%) (p < 0.01). The MC that changed turned more to type II (55.5%) than type III (29%) or the oligoclonal type (15.5%) (p = 0.0002). MC vasculitis (purpura, arthralgia, peripheral neuropathy, renal involvement) and other extrahepatic manifestations (polyarteritis nodosa, lymphoma) in 60/125 patients was associated with advanced age (p < 0.01), a longer duration of infection (p < 0.05), type II MC (odds ratio = 5, p < 0.01), and a higher MC serum level (p < 0.01). CONCLUSION: During chronic active HCV infection, type II MC is more stable over time than type III and oligoclonal MC. The oligoclonal type appears to be an intermediate stage in the course of type III changing to type II MC. Symptomatic persistent HCV MC was associated with advanced age, longer duration of HCV infection, type II MC, and a higher MC serum level.