Extrahepatic Manifestations of Hepatitis C Infection

Abstract

Chronic infection with the hepatitis C virus (HCV) is a major cause of liver disease worldwide and is also responsible for extrahepatic manifestations (EHM) involving many different organs and apparatus: skin, salivary glands, eyes, thyroid, kidneys, peripheral and central nervous system, and immune system. Mixed cryoglobulinemia is the most frequent, best known and strictly HCV-associated EHM. A significant association between HCV and B-cell Non-Hodgkin-Lymphoma is reported although the incidence of lymphoma among HCV-infected patients overall remains low. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular disorders. 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. Because of this associations, it is suggested testing for HCV infection the patients with a clinical condition described as linked to hepatitis C. Conversely, patients diagnosed with HCV infection should have evaluation for a possible EHM. EHM of HCV can be considered an established indication for antiviral treatment with direct acting antivirals, even in the absence of overt liver disease. Successful eradication of HCV can improve and in some cases cure EHM of HCV. B cell depleting agents may be considered to be the best biological target option for patients with more severe EHM in combination with the antivirals.