Genetic polymorphisms of HLA-DP and isolated anti-HBc are important subsets of occult hepatitis B infection in Indonesian blood donors: a case-control study

Abstract

BackgroundOccult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the serum and/or liver in HBsAg-negative individuals. OBI is associated with the risk of viral transmission, especially in developing countries, and with progressive liver disease and reactivation in immunosuppressive patients. The objective of this study was to evaluate the relation of OBI to HLA-DP single nucleotide polymorphisms (SNPs) encoding antigen-binding sites for the immune response to HBV infection. As HLA-DP variants affect the mRNA expression of HLA-DPA1 and HLA-DPB1 in the liver, we hypothesised that high levels of HLA-DPA1 and HLA-DPB1 expression favour OBI development.MethodsThe study enrolled 456 Indonesian healthy blood donors (HBsAg negative). OBI was defined as the presence of HBV-DNA in at least two of four open reading frames (ORFs) of the HBV genome detected by nested PCR. SNPs in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs2281388) were genotyped using real-time Taqman® genotyping assays.ResultsOf 122 samples positive for anti-HBs and/or anti-HBc, 17 were determined as OBI. The minor allele in rs3077 was significantly correlated with OBI [odds ratio (OR) = 3.87, 95% confidence interval (CI) = 1.58–9.49, p = 0.0015]. The prevalence of the minor allele (T) was significantly higher in subjects with OBI than in those without (59% and 33%, respectively). The combination of haplotype markers (TGA for rs3077–rs3135021–rs9277535) was associated with increased risk of OBI (OR = 4.90, 95%CI = 1.12–21.52 p = 0.038). The prevalence of OBI was highest in the isolated anti-HBc group among the three seropositive categories: anti-HBs <500 mIU/ml, anti-HBs ≥500 mIU/ml, and isolated anti-HBc (29.41%, p = 0.014).ConclusionGenetic variants of HLA-DP and the presence of anti-HBc are important predictors of OBI in Indonesian blood donors.Trial registrationRef: KE/FK/194/EC; registered 01 March 2013. Continuing approval Ref: KE/FK/536/EC; registered 12 May 2014.Electronic supplementary materialThe online version of this article (10.1186/s12985-017-0865-7) contains supplementary material, which is available to authorized users.

GWAS identifying HLA‐DPB1 gene variants associated with responsiveness to hepatitis B virus vaccination in Koreans: Independent association of HLA‐DPB1*04:02 possessing rs1042169 G ‐ rs9277355 C ‐ rs9277356 A

“…Additionally, rs872956 in HLA‐DPB1 was associated with HBV reactivation, and the mRNA expression of HLA‐DPB1 was lower in the HBV reactivated group after treatment with immunomodulatory agents . The rs3077 T in HLA‐DP was related to an increased risk of occult hepatitis B infection in an Indonesian population and HBsAg seroclearance in Caucasians . Collectively, these findings imply that a relationship exists between HLA‐DP variants and the host immune response after HBV infection …”

Variation of HLA-DPB1 Gene in Hepatitis B Infection

“…Subsequently, the genotypes of DPB1 * 05:01, 09:01, and DPB1 * 02:01, 04:01, and 04:02 were again found to be susceptible to HBV in Japanese [9] and Chinese [10] populations. The studies also found that some DPB1 alleles and rs9277535G related to weak HBV vaccines response [23] , low sensitive of HBV drug therapy [15] , incidence of occult HBV infection [24] , and also prone to hepatocellular carcinoma development [25] . In our study, we found the strongly association between rs9277535 and HLA-DPB1 alleles and HBV infection susceptibility.…”

Sarcopenia and intramuscular fat deposition are associated with poor survival in Indonesian patients with hepatocellular carcinoma: a retrospective study

“…In addition, we only included patients enrolled in Yogyakarta Province Hospital (RSUP Dr. Sardjito), a tertiary hospital that receives patients referred from several provinces in Indonesia. Furthermore, although the patients included were mostly Javanese, it is the most prevalent ethnic population in Indonesia (40.06%) [5].…”

“…In Indonesia, liver cancer is the fifth most commonly diagnosed cancer and was the fourth leading cause of cancer-related deaths in 2012 [4]. Because of its endemicity of hepatitis B virus (HBV) infection, which is the third-highest prevalence worldwide, HBV is regarded as the leading cause of HCC in Indonesia [5]. A previous study performed in Indonesia demonstrated that most patients are diagnosed at intermediate to advanced stages (Barcelona Clinic Liver Cancer [BCLC] stage B or C), are relatively young (mean age, 54 years), and have a poor prognosis with a median overall survival of 138 days [6].…”