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HCV infection is a major global health threat. HCV is estimated to infect ~71.1 million persons worldwide and to cause approximately 400 000 deaths annually.1 Although HCV-related mortality is reportedly due to the end-stage complications of chronic hepatitis C (decompensated cirrhosis and hepatocellular carcinoma), the above official figures do not take into consideration the mortality attributable to the multifaceted extrahepatic disorders caused by this pathogen.2 3 The list of such extrahepatic manifestations (EHM) is long and includes—but is not limited to—the cryoglobulinaemia-associated syndrome (characterised by fatigue, arthralgia, skin vasculitis, glomerulonephritis and cerebritis, among others), some subtypes of non-Hodgkin’s B cell lymphoma, insulin resistance (which may progress to type 2 diabetes and its cardiovascular sequelae) and various neurological conditions, such as cognitive dysfunction. The causal link between most of these EHM and HCV infection has been established, thanks to a wealth of epidemiological and clinical data, and especially based on the repeated observation that treatment-induced viral clearance is associated with clinical improvement.2 Their pathogenesis encompasses direct and indirect mechanisms, and may involve autoimmune reactions. Incidentally, for the latter reason, some EHMs have been for long time considered a contraindication to interferon (IFN)-α therapy. The recent advent …
Contributors FN wrote the entire manuscript.
Competing interests The corresponding author has received research grant from Gilead Sciences, and is advising Merck, Gilead and AbbVie.
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Provenance and peer review Commissioned; internally peer reviewed.