Extra-hepatic Morbidity and Mortality of Chronic Hepatitis C

Chronic hepatitis C virus (HCV) infection is associated with several extra-hepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B cell non-Hodgkin’s lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurologic manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extra-hepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extra-hepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alpha and ribavirin was shown to improve some of these extra-hepatic effects: sustained virologic response is associated with resolution of complications of cryoglobulinemia, reduced levels of insulin resistance, reduced incidence of diabetes and stroke, and improved fatigue and cognitive functioning. The availability of new interferon-free, well-tolerated anti-HCV treatment regimens is broadening the spectrum of patients available for therapy, including those in whom interferon was contraindicated, and will likely result in greater improvements in the extra-hepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extra-hepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.