• Elena Treppo, Luca Quartuccio, Gaafar Ragab, and Salvatore DE Vita.
• Department of Medicine, Rheumatology Clinic, University of Udine, ASUFC, Udine, Italy.
• Minerva Med. 2021 Apr 1; 112 (2): 201-214.

IntroductionHepatitis C Virus (HCV) is a well-known worldwide infection, responsible for hepatic and extrahepatic complications. Among extrahepatic manifestation, the rheumatologic are the most common ones. With the arrival of Direct Antiviral Agents (DAA), the treatment and the clinical perspective have rapidly changed, permitting to achieve a sustained virological response (SVR) and preventing complications of chronic infection.Evidence AcquisitionWe performed on PubMed a literature search for the articles published by using the search terms "HCV infection," "HCV syndrome," "HCV-related rheumatologic disorders," "cryoglobulinemia," "cryoglobulinemic vasculitis" and "mixed cryoglobulinemia."Evidence SynthesisMixed cryoglobulinemia (MC) is the prototype of HCV-associated rheumatologic disorder. HCV-related MC is typically considered by physicians as a human model disease to linking infection with autoimmune diseases. Chronic HCV infection can lead to a multistep process from a simple serological alteration (presence of circulating serum cryoglobulins) to frank systemic vasculitis (cryoglobulinemic vasculitis [CV]) and ultimately to overt malignant B lymphoproliferation (such as non-Hodgkin lymphoma [NHL]). Antiviral therapy is indicated to eradicate the HCV infection and to prevent the complications of chronic infection. Immunosuppressive therapy is reserved in case of organ threatening manifestations of CV. In this review, we discuss the main clinical presentation, diagnostic approach and treatment of rheumatologic manifestations of HCV infection.ConclusionsChronic HCV infection is responsible for complex clinical condition, ranging from hepatic to extra-hepatic disorders. Cryoglobulins are the result of this prolonged immune system stimulation, caused by tropism of HCV for B-lymphocyte.

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