{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T14:56:09Z","timestamp":1761663369981,"version":"build-2065373602"},"reference-count":16,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T00:00:00Z","timestamp":1434672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms160614075","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T10:23:33Z","timestamp":1434709413000},"page":"14075-14085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Successful and Safe Long-Term Standard Antiviral Therapy  in a Patient with \u201cExplosive\u201d Immune Response in Course of HCV-Related Liver Cirrhosis"],"prefix":"10.3390","volume":"16","author":[{"given":"Paolo","family":"Conca","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Cafaro","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amalia","family":"De Renzo","sequence":"additional","affiliation":[{"name":"Haematology Unit, Federico II University Medical School of Naples, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Coppola","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernesto","family":"Cimino","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7751-2715","authenticated-orcid":false,"given":"Giovanni","family":"Tarantino","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8916","DOI":"10.3748\/wjg.v19.i47.8916","article-title":"Immunological alterations in hepatitis C virus infection","volume":"19","author":"Calvaruso","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"502156","DOI":"10.1155\/2012\/502156","article-title":"Hepatitis C virus infection and mixed cryoglobulinemia","volume":"2012","author":"Lauletta","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7889","DOI":"10.3748\/wjg.v19.i44.7889","article-title":"Direct effects of hepatitis C virus on the lymphoid cells","volume":"19","author":"Kondo","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"807351","DOI":"10.1155\/2012\/807351","article-title":"Pathogenetic Mechanisms of Hepatitis C Virus-Induced B-Cell Lymphomagenesis","volume":"2012","author":"Forghieri","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7874","DOI":"10.3748\/wjg.v19.i44.7874","article-title":"Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment","volume":"19","author":"Carbone","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S201","DOI":"10.1007\/s11739-012-0825-6","article-title":"The hepatitis C virus infection as a systemic disease","volume":"7","author":"Zignego","year":"2012","journal-title":"Intern. Emerg. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1136\/annrheumdis-2012-202770","article-title":"Peg-IFN\u03b1\/ribavirin\/protease inhibitor combination in hepatitis C virus associated mixed cryoglobulinemia vasculitis: Results at week 24","volume":"73","author":"Saadoun","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_8","first-page":"933","article-title":"Efficacy and safety of peginterferon alfa-2b plus ribavirin for HCV-positive mixed cryoglobulinemia: A multicentre open-label study","volume":"29","author":"Mazzaro","year":"2011","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1002\/jmv.23562","article-title":"Antiviral therapy of symptomatic HCV-associated mixed cryoglobulinemia: meta-analysis of clinical studies","volume":"85","author":"Fabrizi","year":"2013","journal-title":"J. Med. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1056\/NEJMoa013376","article-title":"Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection","volume":"347","author":"Hermine","year":"2002","journal-title":"N. Engl. J. 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Gastroenterol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/6\/14075\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:48:08Z","timestamp":1760215688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/6\/14075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,19]]},"references-count":16,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,6]]}},"alternative-id":["ijms160614075"],"URL":"https:\/\/doi.org\/10.3390\/ijms160614075","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2015,6,19]]}}}