title: Extrahepatic morbidity and mortality of chronic hepatitis C.
abstract: Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B-cell non-Hodgkin lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurological manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extrahepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extrahepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alfa and ribavirin was shown to improve some of these extrahepatic effects; sustained virological 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 extrahepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.
authors: Division of Gastroenterology and Hepatology and Division of Clinical Pathology, University Hospital, Geneva, Switzerland.
authors: Francesco
authors: F
authors: Negro
authors: Department of Gastroenterology and Hepatology, St George's Hospital, London, England.
authors: Daniel
authors: D
authors: Forton
authors: Gastroenterology and Internal Medicine, University of Palermo, Palermo, Italy.
authors: Antonio
authors: A
authors: Craxì
authors: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Mark S
authors: MS
authors: Sulkowski
authors: Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Ontario, Canada.
authors: Jordan J
authors: JJ
authors: Feld
authors: Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Hannover, Germany. Electronic address: manns.michael@mh-hannover.de.
authors: Michael P
authors: MP
authors: Manns
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D003449:Cryoglobulinemia / Q000453:epidemiology / Q000821:virology; D005921:Glomerulonephritis / Q000453:epidemiology / Q000821:virology; D044882:Glucose Metabolism Disorders / Q000453:epidemiology / Q000821:virology; D016174:Hepacivirus / Q000187:drug effects* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology / Q000401:mortality* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D008223:Lymphoma / Q000453:epidemiology / Q000821:virology; D009017:Morbidity; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D014657:Vasculitis / Q000453:epidemiology / Q000821:virology
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin
keywords: Cardiovascular Risk; Cryoglobulins; Fatigue; Health-Related Quality of Life; Insulin Resistance