Introducing treat-to-target strategies of autoimmune extrahepatic manifestations of chronic hepatitis C virus infection

The hepatitis C virus (HCV) is recognized as one of the hepatic viruses most often associated with extrahepatic manifestations (EHMs). It is currently accepted that cryoglobulinemic vasculitis (CV) is the key autoimmune extrahepatic disease associated with HCV infection. Therapeutic approaches have mainly been based on the use of old antiviral interferon (IFN)-based regimens and immunosuppressive therapies, often with an inadequate balance between therapeutic benefits and excess side effects. Areas covered: Therapeutic management of HCV patients with EHMs, including both non-autoimmune (cardiovascular, hematological, general features) and autoimmune complications (organ-specific and systemic autoimmune diseases). Therapies included antiviral (IFN, ribavirin, direct-acting antivirals - DAAs-) and non-antiviral (immunosuppressive agents, rituximab, plasma exchanges) options. The review analyses the current evidence for proposing a treat-to-target (T2T) approach for HCV-related autoimmune EHMs based on an organ-by-organ strategy. Expert commentary: Eradication of HCV must be considered the key T2T in the therapeutic approach to HCV-related EHMs, as there has been a disruptive change due to the appearance of direct-acting antivirals (DAAs) as game-changers in HCV therapy, with an efficacy reaching nearly 100%. In this scenario, the central role played until now by IFN and ribavirin is not currently supported and they will not be used in the future.