Extrahepatic Manifestations of Hepatitis C Virus Infection

Abstract

The hepatitis C virus (HCV) is a hepatotropic virus that causes liver cirrhosis and hepatocellular cancer, but it is now considered a systemic disease because of the additional HCV-associated extrahepatic manifestations (EHMs) that occur. HCV infection is a global health problem, with 150–170 million people being chronically infected. It is estimated that about 350,000 patients die from HCV-related complications. However, the risks of mortality and morbidity are underestimated because studies do not take into account extrahepatic outcomes of chronically infected HCV patients. Extrahepatic complications of HCV infection have been shown to be more prevalent in large cohort studies, where two thirds of patients chronically infected with HCV infection have experienced EHMs (Cacoub et al., Arthritis Rheum 42:2204–2212, 1999; El-Serag et al., Hepatology 36:1439–1445, 2002). Some of these EHMs are well documented and more common, while others are rare or their association with HCV is unproven. HCV-associated autoimmune or lymphoproliferative disorders, from benign mixed cryoglobulinemia to frank lymphomas, have been reported. More recently, many other extrahepatic HCV-related disorders have been reported, including cardiovascular, renal, metabolic, and central nervous system diseases. Viral eradication of HCV has significantly reduced the rates of hepatic and extrahepatic deaths (Cacoub et al., Arthritis Rheum 42:2204–2212, 1999; Adinolfi et al., World J Gastroenterol 20:3410–3417, 2014; Zignego et al., Dig Liver Dis 39:2–17, 2007; Lee et al., J Infect Dis 206:469–477, 2012; Omland et al., Clin Gastroenterol Hepatol 9:71–78, 2011; Uto et al., Hepatology 50:393–399, 2009; Hsu et al., Hepatology 59:1293–1302, 2014). The aim of this chapter is to give a brief objective approach to the epidemiology, pathogenesis, and treatment of HCV-associated EHMs.