title: Successful and Safe Long-Term Standard Antiviral Therapy in a Patient with "Explosive" Immune Response in Course of HCV-Related Liver Cirrhosis.
abstract: Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential detail in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ and non-organ-specific autoantibody production up to overt non-Hodgkin's lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, including rheumatoid factor (RF) and cryo- and non-cryoprecipitable immune complexes, as well as clinical manifestations, comprising dermatitis, polyarthralgias and arthritis, pulmonary disease, aplastic anemia, glomerulonephritis and vasculitis. The mechanism of these extra-hepatic disorders is thought of as linked to immune complex disease, but their pathogenesis is poorly clarified. Immune-suppressive treatment could induce high-level hepatitis C viremia and impair hepatic disease. We report a female patient, whose chronic HCV-related liver cirrhosis with associated explosive, but oligosymptomatic lymphoproliferative immune response, i.e., RF beyond three thousand times the upper of normal range (unr), type II cryoglobulinemia with cryocrit 40% and monoclonal gammopathy IgM-k, has been successfully and safely treated by long-lasting (sixty-six months) combined antiviral therapy (pegylated interferon alfa and ribavirin), at moderate and tapering dose regimen, prolonged for nearly 24 months after the first viral suppression. At the last follow-up (fifty-one months), the patient was showing very-long term antiviral response, progressive decline of secondary immune activation and absence of significant side-effects. Further research is required to fully verify the real impact on therapeutic choice/regimen.
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy. paolo.conca@unina.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Conca
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy. giovanni.cafaro@hotmail.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cafaro
authors.affiliation: Haematology Unit, Federico II University Medical School of Naples, 80131 Naples, Italy. amalia.derenzo@unina.it.
authors.forename: Amalia
authors.initials: A
authors.lastname: De Renzo
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy. antocopp@unina.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Coppola
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy. ernesto.cimino@unina.it.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Cimino
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy. tarantin@unina.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tarantino
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000209:etiology; D003449:Cryoglobulinemia / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007075:Immunoglobulin M / Q000187:drug effects / Q000276:immunology*; D008103:Liver Cirrhosis / Q000821:virology*; D008875:Middle Aged; D011379:Prognosis
chemical_list: D000998:Antiviral Agents; D007075:Immunoglobulin M
keywords: antiviral treatment; cryoblobulins; hepatitis C infection; lymphoproliferative disorders; rheumatoid factor