Abstract
The hepatitis C virus (HCV) is both hepatotropic and lymphotropic, responsible for a great number of hepatic and extrahepatic immune-system disorders that comprise the so-called HCV syndrome. HCV-associated rheumatic diseases are characterized by frequent clinico-serological overlap; therefore, correct classification of individual patients is necessary before therapeutic decisions are made. This is particularly difficult to do, however, because of the coexistence of viral infection and complex autoimmune alterations. In this context, mixed cryoglobulinemia syndrome (MCs) represents the prototype of virus-related autoimmune-lymphoproliferative diseases. MCs can be treated at different levels by means of etiological treatment with antivirals (peg-interferon-alpha plus ribavirin) aimed at HCV eradication and/or pathogenetic/symptomatic treatments directed to both immune-system alterations and the vasculitic process (rituximab, cyclophosphamide, steroids, plasmapheresis, and so on). In clinical practice, the therapeutic strategy should be modulated according to severity/activity of the MCs and possibly tailored to each individual patient's conditions. Cryoglobulinemic skin ulcers may represent a therapeutic challenge, which should be managed by means of both local and systemic treatments. HCV-associated arthritis should be differentiated from the simple comorbidity of HCV infection and classical rheumatoid arthritis. It may be treated with low doses of steroids and/or hydroxychloroquine; the use of biologics (rituximab) may be considered in more severe cases. Primary Sjögren's syndrome is rarely associated with HCV infection, while sicca syndrome and myalgia are frequently detectable in hepatitis C patients, with or without cryoglobulinemic vasculitis. Other autoimmune rheumatic disorders (poly/dermatomyositis, polyarteritis nodosa, osteosclerosis, fibromyalgia, and so on) have been reported as potentially associated with HCV infection in patient populations from different countries, suggesting the role of genetic and/or environmental co-factors. The therapeutic approach to these disorders should be decided according to each individual patient's evaluation, including hepatic, virological, and immunological findings.
Highlights
Following the discovery of hepatitis C virus (HCV) in 1989 as the major etiological agent of non-A-non-B chronic hepatitis [1], some epidemiological studies suggested its possible role in the pathogenesis of mixed cryoglobulinemia syndrome (MCs), which represents the prototype of HCV-associated autoimmunelymphoproliferative disorders [1,2,3,4]
HCV infection is the underlying condition that generally precedes by a long time interval the clinical appearance of extrahepatic diseases
The same immunological alterations may be observed in a significant percentage of individuals with isolated HCV infection [1,6]
Summary
Following the discovery of hepatitis C virus (HCV) in 1989 as the major etiological agent of non-A-non-B chronic hepatitis [1], some epidemiological studies suggested its possible role in the pathogenesis of mixed cryoglobulinemia syndrome (MCs), which represents the prototype of HCV-associated autoimmunelymphoproliferative disorders [1,2,3,4]. MCs represents the crossroad between classical rheumatic diseases, such as rheumatoid arthritis (RA) and primary Sjögren’s syndrome (pSS), and other autoimmune lymphoproliferative disorders [1] (Figure 1) It is characterized by the typical clinical triad of purpura, weakness, and arthralgias and by multisystem organ involvement [1,2]. Some studies have suggested that sequential or combined antiviral and immunosuppressive therapy could represent a rather useful therapeutic strategy for treating MCs [18,25,26] This more aggressive treatment could be indicated in patients with major clinical manifestations and/or inadequate remission after standard treatments. Even if a possible causative role of HCV in these autoimmune diseases cannot be totally excluded, these patients might be better classified as having a simple comorbidity They invariably represent a troublesome clinical condition, mainly with regards to therapeutic approach. These latter may be based on standard immunosuppressive treatments, possibly integrated by sequential/combined antiviral treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
