Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis C Virus Infection

SIMPLE SUMMARY: Hepatitis C is a liver infection caused by the hepatitis C virus and is a major health problem that contributes to the global burden of chronic disease. Chronic infection can lead to liver cancer and death from end-organ damage. Despite the introduction of novel anti-viral therapy, the disease burden is still high. This review focuses on the various extrahepatic manifestations of the hepatitis C virus, including frequency, mechanism, and outcomes. Despite the introduction of direct-acting antiviral drugs which have more than a 90% rate of sustained virologic responses, about one-third of patients with chronic HCV infections still develop at least one extrahepatic manifestation. ABSTRACT: Hepatitis C virus (HCV) is a significant cause of chronic liver diseases worldwide and is associated with negative consequences, including cirrhosis, hepatic decompensation, hepatocellular carcinoma, and increased risk of mortality. In addition to liver-related morbidities, HCV is also associated with several extrahepatic manifestations, including mixed cryoglobulinemia, diabetes mellitus, cardiocerebrovascular disease, lymphoma, and autoimmune diseases. These non-liver-related complications of HCV increase the complexity of this disease and can contribute to the economic burden, morbidity, quality of life, and mortality throughout the world. Therefore, understanding how this virus can contribute to each extrahepatic manifestation is worth investigating. Currently, the advancement of HCV treatment with the advent of direct-acting anti-viral agents (DAAs) has led to a high cure rate as a result of sustained virologic response and tremendously reduced the burden of extrahepatic complications. However, HCV-associated extrahepatic manifestations remain a relevant concern, and this review aims to give an updated highlight of the prevalence, risk factors, associated burdens, and treatment options for these conditions.