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World J Gastroenterol. May 7, 2007; 13(17): 2467-2478
Published online May 7, 2007. doi: 10.3748/wjg.v13.i17.2467
Hepatitis C virus-related lymphoproliferative disorders: An overview
Anna Linda Zignego, Carlo Giannini, Clodoveo Ferri
Anna Linda Zignego, Carlo Giannini, Department of Internal Medicine, Center for Systemic Manifestations of Hepatitis Viruses (MASVE) and Center for Research, Transfer and High Education DENOThe, University of Florence, Medical School, Florence, Italy
Clodoveo Ferri, Rheumatology Unit, Department of Internal Medicine, Medical School, University of Modena and Reggio Emilia, Modena, Italy
Author contributions: All authors contributed equally to the work.
Correspondence to: Anna Linda Zignego, MD, PhD, Professor of Medicine, Department of Internal Medicine, University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
Telephone: +39-055-4296483 Fax: +39-055-417123
Received: March 7, 2007
Revised: March 8, 2007
Accepted: March 12, 2007
Published online: May 7, 2007

Hepatitis C virus (HCV) is a global health problem affecting 3% of the world's population (about 180 million) and a cause of both hepatic and extrahepatic diseases. B-cell lymphoproliferative disorders, whose prototype is mixed cryoglobulinemia, represent the most closely related as well as the most investigated HCV-related extrahepatic disorder. The association between extrahepatic (lymphoma) as well as hepatic malignancies (hepatocellular carcinoma) has justified the inclusion of HCV among human cancer viruses. HCV-associated manifestations also include porphyria cutanea tarda, lichen planus, nephropathies, thyreopathies, sicca syndrome, idiopathic pulmonary fibrosis, diabetes, chronic polyarthritis, sexual dysfunctions, cardiopathy/atherosclerosis, and psychopathological disorders. A pathogenetic link between HCV virus and some lymphoproliferative disorders was confirmed by their responsiveness to antiviral therapy, which is now considered the first choice treatment. The aim of the present paper is to provide an overview of extrahepatic manifestations of HCV infection with particular attention to B-cell lymphoproliferative disorders. Available pathogenetic hypotheses and suggestions about the most appropriate, currently available, therapeutic approaches will also be discussed.

Keywords: Hepatitis C virus, Extrahepatic manifestations, Lymphoproliferative disorders, Mixed cryoglobulinemia, Lymphoma