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Chronic infection with the hepatitis C virus (HCV) is a slow progressive disease. While fibrosis development may not be linear over time, it has been estimated that 15–20% of patients will establish cirrhosis within 20 years of HCV acquisition.1 Once cirrhosis is present, it is clear that the patient's prognosis is heavily affected, with a 3–5% annual risk of liver failure as well as hepatocellular carcinoma (HCC). Although liver transplantation may be lifesaving in selected cases, organ shortage remains an important limitation. As a result, cirrhosis-related complications are considered to be one of the main reasons why chronic HCV infection is associated with an impaired overall survival.2 Fortunately, many HCV-infected patients are not expected to develop advanced hepatic fibrosis. Are these patients unaffected by the virus? Probably not. Chronic HCV infection remains a multifaceted disease, which is not restricted to the liver. Patients may experience a variety of liver-unrelated discomforts such as fatigue, nausea, abdominal or musculoskeletal pain, loss of weight, and neuropsychiatric symptoms including depression, irritability and malaise. These symptoms are non-specific and can often be attributed to extrahepatic manifestations of HCV infection. Extrahepatic manifestations are reported in up to 74% of patients, can be present long before the stage of advanced liver disease, and may be largely responsible for the frequent impaired health-related quality of life among patients with chronic HCV infection.3 Among the best known manifestations are mixed …
Competing interests AJvdM received financial compensation for lecture activities from MSD and Gilead.
Provenance and peer review Commissioned; internally peer reviewed.