Published online Mar 27, 2015. doi: 10.4254/wjh.v7.i3.327
Peer-review started: August 31, 2014
First decision: November 14, 2014
Revised: December 27, 2014
Accepted: January 9, 2015
Article in press: January 9, 2015
Published online: March 27, 2015
The clinical course of chronic hepatitis C virus (HCV) infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several immune-mediated disorders; a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion of patients with HCV infection, are responsible for the production of different autoantibodies and immune-complexes, such as mixed cryoglobulins. These serological alterations may characterize a variety of autoimmune or neoplastic diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated and lymphoproliferative disorders; interestingly, in some cases the disease may evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential as suggested by several clinico-epidemiological and laboratory studies; in addition to hepatocellular carcinoma that represents the most frequent HCV-related malignancy, a causative role of HCV has been largely demonstrated in a significant percentage of patients with isolated B-cells non-Hodgkin’s lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCV-related thyroid involvement. Patients with HCV infection are frequently asymptomatic or may develop only hepatic alteration, while a limited but clinically relevant number can develop one or more autoimmune and/or neoplastic disorders. Given the large variability of their prevalence among patients’ populations from different countries, it is possible to hypothesize a potential role of other co-factors, i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra-hepatic diseases.
Core tip: The proposed definition of hepatitis C virus (HCV) syndrome encompasses the multiform complex of clinico-pathological conditions potentially correlated to chronic HCV infection. The natural history of HCV syndrome is the result of multifactorial and multistep pathogenetic process, which usually proceeds from mild, often isolated manifestations, to systemic immune-mediated disorders, and less frequently to overt malignancies. Here we analyze the clinical, epidemiological, and pathogenetic aspects of this multifaceted condition, including the updated results of the world literature.