Review
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World J Immunol. Jul 27, 2014; 4(2): 52-62
Published online Jul 27, 2014. doi: 10.5411/wji.v4.i2.52
Gut immune response in the presence of hepatitis C virus infection
Helal F Hetta, Minesh J Mehta, Mohamed Tarek M Shata
Helal F Hetta, Minesh J Mehta, Mohamed Tarek M Shata, Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH 45267, United States
Helal F Hetta, Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
Author contributions: All the authors contributed to this paper.
Supported by Egyptian Government Scholarship for Helal Hetta; and Merck Investigator Initiated Studies (IIS) IISP, No. 40458 (Shata)
Correspondence to: Mohamed Tarek M Shata, MD, PhD, Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, 231 Albert B. Sabin Way, Cincinnati, OH 45267, United States. mohamed.shata@uc.edu
Telephone: +1-513-5586110 Fax: +1-513-5581744
Received: April 2, 2014
Revised: May 22, 2014
Accepted: June 20, 2014
Published online: July 27, 2014
Processing time: 116 Days and 7.5 Hours
Abstract

Hepatitis C virus (HCV) is an important etiologic agent of hepatitis and a major cause of chronic liver infection that often leads to cirrhosis, fibrosis and hepatocellular carcinoma. Although, HCV is a hepatotropic virus, there is strong evidence that HCV could replicate extra-hepatic in the gastrointestinal tissue which could serve as a reservoir for HCV. The outcome of HCV infection depends mainly on the host innate and adaptive immune responses. Innate immunity against HCV includes mainly nuclear factor cells and activation of IFN-related genes. There is an immunologic link between the gut and the liver through a population of T-cells that are capable of homing to both the liver and gut via the portal circulation. However, little is known on the role of Gut immune response in HCV. In this review we discussed the immune regulation of Gut immune cells and its association with HCV pathogenesis, various outcomes of anti-HCV therapy, viral persistence and degree of liver inflammation. Additionally, we investigated the relationship between Gut immune responses to HCV and IL28B genotypes, which were identified as a strong predictor for HCV pathogenesis and treatment outcome after acute infection.

Keywords: Hepatitis C virus; Colonic Treg; Mucosal; Immune regulation; Liver inflammation; Interleukin-28B

Core tip: Chronic hepatitis C (CHC) is a global worldwide health problem with approximately 200 million people worldwide infected with hepatitis C virus (HCV). It is also a major cause of chronic liver infection that often leads to chronic hepatitis which may progress to cirrhosis, fibrosis and finally hepatocellular carcinoma. In CHC, immune responses play an important role in HCV pathogenesis and responses to therapy. Intra-hepatic immune responses to HCV are highly regulated. There is a clear relationship between hepatic immune responses and mucosal immune response in the gut. Additionally, genetic immunological markers have been proposed to predict response to HCV treatment, and outcome of infection.