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World J Gastroenterol. Dec 21, 2013; 19(47): 8910-8915
Published online Dec 21, 2013. doi: 10.3748/wjg.v19.i47.8910
Hepatitis C virus-related mixed cryoglobulinemia: Is genetics to blame?
Laura Gragnani, Elisa Fognani, Alessia Piluso, Anna Linda Zignego
Laura Gragnani, Elisa Fognani, Alessia Piluso, Anna Linda Zignego, Center for Systemic Manifestations of Hepatitis Viruses, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Author contributions: All the authors contributed to this manuscript.
Supported by Grants from the “Associazione Italiana per la Ricerca sul Cancro” Investigator Grant, No. 1461; ‘‘Istituto Toscano Tumori’’; “Fondazione Istituto di Ricerche Virologiche Oretta Bartolomei Corsi”; “Ente Cassa di Risparmio di Firenze”
Correspondence to: Anna Linda Zignego, MD, PhD, Center for Systemic Manifestations of Hepatitis Viruses, Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy. a.zignego@dmi.unifi.it
Telephone: +39-55-4271077 Fax: +39-55-7947330
Received: September 27, 2013
Revised: October 28, 2013
Accepted: November 12, 2013
Published online: December 21, 2013
Processing time: 115 Days and 16.5 Hours
Abstract

Mixed cryoglobulinemia (MC) is the extrahepatic manifestation most strictly correlated with hepatitis C virus (HCV) infection; it is a benign autoimmune and lymphoproliferative disorder that evolves to lymphoma in 5%-10% of cases. MC is reputed to be a multistep and multifactorial process whose pathogenicity is still poorly understood. It is still unknown why only some chronically infected HCV patients develop MC and only some of these exhibit systemic symptoms (MC syndrome). Several studies have investigated the pathogenetic basis of MC and the most recent ones suggest that the virus is able to trigger such a disorder only in the presence of genetic factors that are still unknown. Here, we try to clarify the complex relationship between HCV-related MC and the host’s genetic background. The data that we report are heterogeneous and sometimes even conflicting. Therefore, large, multicenter studies are clearly needed. The identification of a characteristic genetic signature of cryoglobulinemic patients would be an important step toward a personalized approach in their clinical care. The new wide-ranging genomics technologies will hopefully help to resolve these complex issues.

Keywords: Hepatitis C virus; Mixed cryoglobulinemia; Genetics; Viral pathogenetic factors; Host pathogenetic factors

Core tip: Mixed cryoglobulinemia (MC) is the extrahepatic manifestation most strictly correlated with hepatitis C virus (HCV) infection; it is a benign autoimmune/ lymphoproliferative disorder that evolves to lymphoma in 5%-10% of cases. MC pathogenesis is still poorly understood. Several studies have tried to clarify the pathogenetic basis of MC and have suggested that HCV can trigger such a disorder only in the presence of still-undetermined genetic factors. Here, we attempt to clarify the relationship between HCV-related MC and the host’s genetic background. The data that we report are heterogeneous and sometimes conflicting, so large, multicenter studies are clearly needed.