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Effect of HLA-DPA1 alleles on chronic hepatitis B prognosis and treatment response.

ABSTRACT: OBJECTIVE:Chronic hepatitis B (CHB) is a major health problem. The outcome of hepatitis B virus (HBV) infection is associated with variations in HLA-DPA1 alleles. The aim of this study was to investigate possible associations of HLA-DPA1 alleles with treatment response and with hepatitis B virus e antigen (HBeAg) seroconversion. METHODS:Eight different HLA-DPA1 alleles from 246 CHB patients were genotyped by polymerase chain reaction with sequence-specific primers at high resolution to investigate the association of HLA-DPA1 alleles with treatment response, development of cirrhosis, HBeAg seroconversion, and disease reoccurrence upon HBeAg loss. RESULTS:There was no significant association between HLA-DPA1 alleles and treatment response, development of cirrhosis, or HBeAg seroconversion. However, HLA-DPA1*04:01 allele was significantly more frequently found in patients who redeveloped disease upon HBeAg seroconversion (100% vs 36.8%: p=0.037; Fisher's exact test). CONCLUSION:HLA-DPA1*04:01 allele may be a risk factor for reoccurrence of CHB after HBeAg seroconversion.

SUBMITTER: Katrinli S

PROVIDER: S-EPMC5336620 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Effect of HLA-DPA1 alleles on chronic hepatitis B prognosis and treatment response.

Katrinli Seyma S Enc Feruze Yilmaz FY Ozdil Kamil K Ozturk Oguzhan O Tuncer Ilyas I Doganay Gizem Dinler GD Doganay Levent L

Northern clinics of Istanbul 20160101 3

<h4>Objective</h4>Chronic hepatitis B (CHB) is a major health problem. The outcome of hepatitis B virus (HBV) infection is associated with variations in HLA-DPA1 alleles. The aim of this study was to investigate possible associations of HLA-DPA1 alleles with treatment response and with hepatitis B virus e antigen (HBeAg) seroconversion.<h4>Methods</h4>Eight different HLA-DPA1 alleles from 246 CHB patients were genotyped by polymerase chain reaction with sequence-specific primers at high resoluti ...[more]

PMID: 28275747

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Project description:The neonatal hepatitis B vaccination (HBVac) was implemented 35 years ago in Taiwan, but many vaccinees exhibit inadequate long-term vaccine-induced seroprotective hepatitis B surface antibody (anti-HBs) levels. We investigated the association of the human leukocyte antigen (HLA) alleles (DPA1, DPB1, DQA1, and DQB1) with the long-term immunological response to the neonatal HBVac and adolescent booster HBVac in a Taiwanese cohort. We divided 281 Han students (median age 22, age range 17-29 years) into the following groups: (1) Group A (n = 61): anti-HBs titer ≥ 10 mIU/mL at the beginning of the study; (2) Group B (n = 75): anti-HBs level > 1000 mIU/mL after the first booster; (3) Group C (n = 37): anti-HBs level < 10 mIU/mL after the first booster; and (4) Group D (n = 5): anti-HBs level < 10 mIU/mL after three boosters. DQA1, DQB1, DPA1, and DPB1 typing of the participants was performed using sequence-specific oligonucleotides. Associations of HLA alleles and haplotypes with effects on neonatal HBVac and booster HBVac were examined through logistic regression analysis and Fisher's exact test. A false discovery rate-based measure of significance, the q-value, was used for multiple comparisons, and an association was considered significant if the corresponding q-value was < 0.1. DPA1 alleles were associated with the long-term immunological response to the neonatal HBVac. The estimated odds ratio (OR) of the lack of HBV protective immunity when carrying an additional DPA1*01 and DPA1*02 was 0.36 [95% confidence interval (CI) = 0.17-0.76, p = 0.0076] and 2.39 (95% CI = 1.17-4.87, p = 0.016), respectively. DPB1 and DQB1 alleles were associated with a response to the adolescent booster vaccination. The estimated ORs of being nonresponsive to the first booster when carrying an additional DPB1*05 and DQB1*02 were 2.11 (95% CI = 1.13-3.93, p = 0.019) and 3.73 (95% CI = 1.43-9.71, p = 0.0070), respectively. All DPB1*03 carriers responded to the first booster (p of Fisher's exact test = 0.0045). In our study, we discovered that HLA-DPA1 was primarily associated with the long-term response of primary infantile HBVac, and HLA-DPB1 and HLA-DQB1 exhibited associations with the HBV booster vaccination.

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Effect of HLA-DPA1 alleles on chronic hepatitis B prognosis and treatment response.

Publications

Effect of HLA-DPA1 alleles on chronic hepatitis B prognosis and treatment response.

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