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.

/pdf/a-comparative-review-of-hla-associations-with-hepatitis-b-14krik13c6.pdf

A comparative review of HLA associations with hepatitis B and C viral infections across global populations.

Considerable evidence suggests that host genetic factor play an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection in several ethic groups. Association study was performed included 150 chronic HBV patients, 100 resolved hepatitis B and 150 healthy individuals with similar ethic background. Interestingly, human leucocyte antigen (HLA)-DR13 show a strong association with the clearance of HBV [odds ratio (OR) = 0.04, 95% confidence interval (CI) = 0.00-0.26, corrected P-value (P(c)) = 0.0008] similar to reports from several ethic groups. TNF-alpha promoter polymorphisms (-863, -308 and -238) were also analysed. Only -863 C allele was found to be significantly decreased in chronic HBV patients compared with healthy control (P(c) = 0.03, OR = 0.54, 95% CI = 0.35-0.84 respectively). This -863C allele was not in linkage disequilibrium with HLA-DR13 suggesting that other genetic markers linked with -863C might influence clearance of chronic HBV infection in Thai. When stratified chronic HBV patients into patients without hepatocellular carcinoma (HCC) and with HCC, the -863 A allele was significantly increased in the HCC group compared to healthy control (P(c) = 0.003, OR = 2.61, 95% CI = 1.49-4.60). Haplotype analysis (-863/-308/-238) revealed that the homozygosity of the haplotype (CGG/CGG) was a protective marker for HCC (OR = 0.37, 95% CI = 0.17-0.79, P(c) = 0.02). One can propose that carriers of -863A genotype are associated with increased levels of TNF-alpha in the liver in response to HBV infection and induce hapatocyte damage that may finally lead to HCC development. Additional study is needed to validate these finding and to further explore the genetic pathogenesis of HBV infection.

Association of HLA-DRB1*13 and TNF-alpha gene polymorphisms with clearance of chronic hepatitis B infection and risk of hepatocellular carcinoma in Thai population.

Impact of host gene polymorphisms on susceptibility to chronic hepatitis B virus infection.

Association of TNF-alpha -308 polymorphism with the outcome of hepatitis B virus infection in Turkey.

Background
The clearance of hepatitis B virus (HBV) is a complex process which may be influenced by many factors including polymorphisms in the tumor necrosis factor (TNF- ) gene promoter. However, previous reports regarding the relationship between polymorphisms in the TNF- promoter and HBV clearance have been inconsistent. Therefore, we performed a meta-analysis on a large population to address this inconsistency.

/pdf/relationship-between-tnf-gene-promoter-polymorphisms-and-2s8o3wqqvl.pdf

Relationship between TNF- gene promoter polymorphisms and outcomes of hepatitis B virus infections: a meta-analysis.

Background: Clearance of hepatitis B virus (HBV) infection requires a good host immune response. Cytokines like tumor necrosis factor-alpha (TNF-α) may play a role in such immune response. Genetic changes in TNF-α gene promoter region are known to influence TNF-α expression. We therefore studied the role of one such mutation in chronic HBV infection. Methods: Presence of -308 G/A polymorphism in the promoter region of TNF-α gene was looked for in 100 patients with chronic HBV infection, 91 subjects with spontaneously recovered HBV infection, and 89 healthy controls, using a PCR-RFLP method. Results: Variant alleles (A/A or A/G) were found in 22 of 100 (22%) patients with chronic HBV infection, 21 of 91 (23%) subjects with spontaneous HBV clearance, and 14 of 89 (15.7%) control subjects (p=ns for inter-group comparisons). Conclusion: TNF-α promoter polymorphism -308A is common in Iranian population, but has no association with development of chronic HBV infection. [Indian J Gastroenterol

Tumor necrosis factor-alpha gene promoter polymorphism in Iranian patients with chronic hepatitis B.

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Tumor necrosis factor-alpha gene promoter polymorphism in Iranian patients with chronic hepatitis B.