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World J Gastroenterol. Nov 21, 2014; 20(43): 16197-16202
Published online Nov 21, 2014. doi: 10.3748/wjg.v20.i43.16197
Hepatitis C infection and lymphoproliferative disease: Accidental comorbidities?
Tawfik Khoury, Shmuel Chen, Tomer Adar, E Ollech Jacob, Meir Mizrahi
Tawfik Khoury, Shmuel Chen, Tomer Adar, E Ollech Jacob, Meir Mizrahi, Department of Internal Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, IL 91120, Israel
Meir Mizrahi, Institute for Gastroenterology and Liver Disease, Hebrew University-Hadassah Medical Center, Jerusalem, IL 91120, Israel
Author contributions: Khoury T and Chen S contributed equally; Mizrahi M study concept and design; Khoury T, Chen S, Adar T, Jacob EO, Mizrahi M acquisition of data; Mizrahi M analysis and interpretation of data; Khoury T, Chen S, Adar T, Jacob EO, Mizrahi M drafting of the manuscript; Khoury T, Chen S, Mizrahi M critical revision of the manuscript for important intellectual content; Chen S technical, or material support; Mizrahi M study supervision; Khoury T, Chen S, Adar T, Jacob EO, Mizrahi M review of the final manuscript prior to submission
Correspondence to: Meir Mizrahi, MD, Institute for Gastroenterology and Liver Disease, Hebrew University-Hadassah Medical Center, POB 12000, Jerusalem, IL 91120, Israel. mizrahim@hadassah.org.il
Telephone: +972-2-6778231 Fax: +972-2-6431021
Received: December 7, 2013
Revised: June 4, 2014
Accepted: June 26, 2014
Published online: November 21, 2014
Processing time: 347 Days and 22.4 Hours
Abstract

Chronic hepatitis C virus (HCV) infection has been associated with liver cancer and cirrhosis, autoimmune disorders such as thyroiditis and mixed cryoglobulinema, and alterations in immune function and chronic inflammation, both implicated in B cell lymphoproliferative diseases that may progress to non-Hodgkin lymphoma (NHL). HCV bound to B cell surface receptors can induce lymphoproliferation, leading to DNA mutations and/or lower antigen response thresholds. These findings and epidemiological reports suggest an association between HCV infection and NHL. We performed a systematic review of the literature to clarify this potential relationship. We searched the English-language literature utilizing Medline, Embase, Paper First, Web of Science, Google Scholar, and the Cochrane Database of Systematic Reviews, with search terms broadly defined to capture discussions of HCV and its relationship with NHL and/or lymphoproliferative diseases. References were screened to further identify relevant studies and literature in the basic sciences. A total of 62 reports discussing the relationship between HCV, NHL, and lymphoproliferative diseases were identified. Epidemiological studies suggest that at least a portion of NHL may be etiologically attributable to HCV, particularly in areas with high HCV prevalence. Studies that showed a lack of association between HCV infection and lymphoma may have been influenced by small sample size, short follow-up periods, and database limitations. The association appears strongest with the B-cell lymphomas relative to other lymphoproliferative diseases. Mechanisms by which chronic HCV infection promotes lymphoproliferative disease remains unclear. Lymphomagenesis is a multifactorial process involving genetic, environmental, and infectious factors. HCV most probably have a role in the lymphomagenesis but further study to clarify the association and underlying mechanisms is warranted.

Keywords: Blood; Hepatitis C infection; Non-Hodgkin’s lymphoma; Pathogenesis; Treatment

Core tip: This is a review of the literature regarding the relationship between hepatitis C virus and lymphoproliferative disease, an issue with unresolved conclusions until today.