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Mixed cryoglobulinemia is the most common extrahepatic manifestation of chronic HCV infection. The disease can occur both asymptomatically and in the form of systemic vasculitis with a wide range of clinical manifestations. The development of cryoglobulinemia is based on relatively benign lymphoproliferation, which, as pathological clones increase and their malignancy can lead to the appearance of B-cell non-Hodgkin's lymphomas. The new treatment of HCV infection with direct acting antivirals allows to achieve an increase in the rate of virus elimination. However, the clinical and, especially, immunological responses associated with the disappearance of cryoglobulins, as well as the normalization of the rheumatoid factor and C4 complement components, were significantly weaker compared to the virological response. Recently, it became known about the possible positive dynamics of these parameters in the future course, but the timing and volume of such observations are clearly insufficient. The persistence of elevated rheumatoid factor values, hypocomplementemia, and, especially, cryoglobulinemia after achieving a sustained virologic response as a result of antiviral therapy raises a number of serious questions relevant for clinical practice. Among the main issues are how often and how quickly normalization of these immunological disorders is possible? What are the consequences of their persistence? Under what conditions is it appropriate to consider alternative approaches to antiviral therapy and to use immunobiological drugs aimed at suppressing B-lymphocyte proliferation? These problems, as well as some aspects of the pathogenesis, clinical course, and treatment of extrahepatic manifestations of chronic HCV infection based on virus-induced lymphoproliferation are discussed in this literature review.

Mixed cryoglobulinemia associated with chronic HCV infection in the era of modern antiviral therapy: Can the problem be considered solved?