Human Leukocyte Antigen Alleles and Haplotypes Associated With Chronicity of Hepatitis B Virus Infection in Koreans

Abstract Context.—Chronic hepatitis B infection is the leading cause of cirrhosis and hepatocellular carcinoma. Human leukocyte antigen may be involved in the chronicity of hepatitis B virus (HBV) infection. Objective.—To analyze the association between HBV chronicity and human leukocyte antigen alleles and haplotypes of 636 organ donors and recipients. Design.—Subjects were categorized into 2 groups according to their clinical and serologic profiles, specifically, an HBV natural convalescent group and an HBV chronic carrier (CC) group. Results.—Hepatitis B chronicity was positively associated with A33 (P = .004, odds ratio [OR] = 1.59) and DR7 (P < .001, OR = 2.58), and negatively associated with HLA-DR13 (P < .001, OR = 0.40). Coexpression of A33 and DR7 was significantly higher in the CC group (OR = 3.63), compared with that of either allele alone (OR = 1.76 in A33; OR = 2.53 in DR7). The statistically significant haplotypes were B44-DR7 (P < .001, OR = 5.44), A33-DR7 (P < .001, OR = 4.47), and A33-B44-DR7 (P < .001, OR = 7.31) in the CC group. Conclusions.—Our results indicate that alleles of A33, DR7, and haplotypes containing DR7 are associated with HBV chronicity among Koreans. Moreover, the 2 antigens had an additive effect on chronicity. These findings support the theory that human leukocyte antigen class I–restricted cytotoxic T cells and human leukocyte antigen class II– restricted helper T cells play an important role in HBV chronicity.

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Relationship of human leukocyte antigen class II genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients

World Journal of Gastroenterology ◽

10.3748/wjg.v11.i36.5721 ◽

2005 ◽

Vol 11 (36) ◽

pp. 5721 ◽

Cited By ~ 17

Author(s):

Yong-Nian Han

Keyword(s):

Hepatitis B Virus ◽

Virus Infection ◽

Hepatitis B ◽

Human Leukocyte Antigen ◽

Human Leukocyte Antigen Class ◽

Human Leukocyte ◽

Hepatitis B Virus Infection ◽

Leukocyte Antigen ◽

B Virus ◽

Relationship Of

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Human leukocyte antigen class I-independent pathways may contribute to hepatitis B virus-induced liver disease after liver transplantation

Hepatology ◽

10.1002/hep.1840180304 ◽

1993 ◽

Vol 18 (3) ◽

pp. 491-496

Author(s):

Gabriele Missale ◽

John J. Brems ◽

Howard Takiff ◽

Paul J. Pockros ◽

Francis V. Chisari

Keyword(s):

Liver Transplantation ◽

Liver Disease ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Human Leukocyte Antigen ◽

Human Leukocyte Antigen Class ◽

Human Leukocyte ◽

Class I ◽

Leukocyte Antigen ◽

B Virus

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Human Leukocyte Antigen Class II Association with Spontaneous Recovery from Hepatitis B Virus Infection in Koreans: Analysis at the Haplotype Level

Journal of Korean Medical Science ◽

10.3346/jkms.2008.23.5.838 ◽

2008 ◽

Vol 23 (5) ◽

pp. 838 ◽

Cited By ~ 12

Author(s):

Sung Won Cho ◽

Jae Youn Cheong ◽

Young Su Ju ◽

Do Hoon Oh ◽

Young Ju Suh ◽

...

Keyword(s):

Hepatitis B Virus ◽

Virus Infection ◽

Hepatitis B ◽

Human Leukocyte Antigen ◽

Human Leukocyte Antigen Class ◽

Spontaneous Recovery ◽

Human Leukocyte ◽

Hepatitis B Virus Infection ◽

Leukocyte Antigen ◽

B Virus

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Human leukocyte antigen class I-independent pathways may contribute to hepatitis B virus-induced liver disease after liver transplantation,

Hepatology ◽

10.1016/0270-9139(93)90346-o ◽

1993 ◽

Vol 18 (3) ◽

pp. 491-496 ◽

Cited By ~ 1

Author(s):

G Missale

Keyword(s):

Liver Transplantation ◽

Liver Disease ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Human Leukocyte Antigen ◽

Human Leukocyte Antigen Class ◽

Human Leukocyte ◽

Class I ◽

Leukocyte Antigen ◽

B Virus

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Hepatitis B infection outcome is associated with novel human leukocyte antigen variants in Ghanaian cohort

Experimental Biology and Medicine ◽

10.1177/1535370220921118 ◽

2020 ◽

Vol 245 (9) ◽

pp. 815-822

Author(s):

Kwesi Z Tandoh ◽

Kwadwo A Kusi ◽

Timothy N Archampong ◽

Isaac Boamah ◽

Osbourne Quaye

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

P Value ◽

Hepatitis B Infection ◽

Virus Persistence ◽

Hla Alleles ◽

Leukocyte Antigen ◽

B Virus

Chronic hepatitis B infection is an important medical problem in sub-Saharan Africa. With increasing concerns of dwindling access to needed care, increasing cost of treatment, and rising prevalence of dire outcomes like liver cirrhosis and hepatocellular cancer, the need to determine the genetic associations underpinning hepatitis B virus persistence or clearance in a population comes to the fore. Genetic association studies have suggested a variation in human leukocyte antigen alleles associated with hepatitis B virus outcome along geo-ethnic lines. We investigated the association of human leukocyte antigen alleles to hepatitis B virus outcome against this backdrop. We used targeted next generation sequencing to type the human leukocyte antigen class I and II alleles of 173 study participants. These comprised of 92 cases with chronic hepatitis B infection and 81 healthy controls with serological evidence of naturally cleared hepatitis B virus infection. We have identified human leukocyte antigen alleles associated with hepatitis B virus clearance and persistence for the first time in a Ghanaian population. The class 1 allele C*16:01 (odds ratio (OR) = 3.4, confidence interval (CI) = 1.6–7.0, P-value = 0.01) was associated with hepatitis B virus persistence. Four class I alleles and one class II allele: A*34:02 (OR = 0.1, CI = 0.04–0.2, P-value = 3.4e-05), A*74:01 (OR = 0.3, CI = 0.2–0.7, P-value = 0.0135), B*13:02 (OR = 0.04, CI = 0.01–0.2, P-value = 0.000172), C*08:04 (OR = 0.06, CI = 0.01–0.2, P-value = 7.83e-05), and DRB1*08:04 (OR = 0.2, CI = 0.03–0.27, P-value = 0.000252) were associated with hepatitis B virus clearance. Our data show that previously reported human leukocyte antigen alleles associations to hepatitis B virus outcome are not found in this Ghanaian study. This study has therefore identified human leukocyte antigen types that are associated with either hepatitis B virus persistence or clearance and highlights the importance of geo-ethnic pivoted studies in determining the genetic associations to acute hepatitis B virus infection outcome. Impact statement Genetic association studies can determine the effect size of gene loci on disease outcomes. In the arena of HBV infections, HLA alleles that associate with HBV outcomes can be used in clinical management decisions. This potential translational utility can shape the future management of HBV infections by identifying at-risk individuals and tailoring medical interventions accordingly. This precision medicine motif is currently only a nascent idea. However, it has stakes that may well override the current “wait and see” approach of clinical management of HBV infections. Here, we have identified HLA alleles associated with HBV outcome in a Ghanaian cohort. Our findings support the motif that HLA alleles associate with HBV outcome along geo-ethnic lines. This buttresses the need for further population pivoted studies. In the long term, our findings add to efforts towards the development of an HLA molecular-based algorithm for predicting HBV infection outcomes.

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