Review
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 28, 2007; 13(12): 1770-1787
Published online Mar 28, 2007. doi: 10.3748/wjg.v13.i12.1770
A comparative review of HLA associations with hepatitis B and C viral infections across global populations
Rashmi Singh, Rashmi Kaul, Anil Kaul, Khalid Khan
Rashmi Singh, Rashmi Kaul, Anil Kaul, Department of Biochemistry and Microbiology, Center of Health Sciences, Oklahoma State University, Tulsa, OK 74107, United States
Khalid Khan, Department of Pediatrics, Division of Gastroenterology, University of Minnesota, United States
Author contributions: All authors contributed equally to the work.
Correspondence to: Rashmi Kaul, PhD, Assistant Professor of Immunology, Department of Biochemistry and Microbiology, Oklahoma States University-Center of Health sciences, 1111 W. 17th St. Tulsa, OK 74107, United States. rashmi.kaul10@okstate.edu
Telephone: +1-918-5611231 Fax: +1-918-5618276
Received: December 25, 2006
Revised: January 26, 2006
Accepted: March 7, 2007
Published online: March 28, 2007
Abstract

Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific therapeutic strategies for clearance of HBV and HCV infections or co-infections across global populations and aid in identification of HBV-HCV combined vaccine. HLA associations of chronic HBV or HCV development with confounding host factors including alcohol, drug abuse, insulin resistance, age and gender are lacking and warrant detailed investigation across global populations.

Keywords: Human leukocyte antigen; HBV persistence; HCV persistence; Interferon response to HBV and HCV; HBV vaccination response