Human Leukocyte Antigen System Likely Plays a Role in Course of HBV Infections

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No association of the 3 single nucleotide polymorphisms with the stages of chronic HBV infection was found.
No association of the 3 single nucleotide polymorphisms with the stages of chronic HBV infection was found.

The human leukocyte antigen (HLA) system likely plays a role in the course of hepatitis B virus (HBV) infections, as the rs3077-T allele has been found to be associated with persistent HBV infection in Caucasians, according to the results of a retrospective case-control study published in Liver International.1

In patients with HBV, the occurrence of long-term complications becomes more frequent over time, especially in patients in the hepatitis phase compared with patients in the HBe antigen (Ag)-negative chronic infection phase and lowest in patients achieving seroclearance of HBsAg with or without the development of anti-HBs antibodies.2,3 HLA single nucleotide polymorphisms (SNPs) were found to be associated with spontaneous HBsAg loss in Asian populations.4-14 

A few studies with ambiguous findings have assessed the influence of HLA-DP polymorphisms on the course of HBV infection in Caucasians.15-18 Therefore, researchers investigated the impact of the rs3077, rs9277535, and rs9277534 single nucleotide polymorphisms (SNPs) on the clinical outcome of HBV infection in 1111 Caucasians, including 618 with chronic HBV infection, 239 with spontaneous HBsAg seroclearance, and 254 healthy controls.1

The researchers found that there was a significant difference in the allele distributions for rs3077 SNP between healthy controls and patients with chronic HBV infection, as well as between patients with seroclearance and patients with chronic HBV infection.  While the rs3077-C allele was associated with a lower probability for spontaneous HBsAg seroclearance compared with the rs3077-T allele (P =.033), no association of the 3 SNPs with the stages of chronic HBV infection was found.

“In conclusion, our results demonstrate for the first time the association of rs3077 with persistent HBV infection in a Caucasian population” stated the investigators.1 They added that, “Further studies are needed to elucidate the role of HLA-DP variants in disease pathogenesis and their potential role for individualized disease management.”

Disclosure: This study was partially supported by a research grant from Gilead Sciences, Inc.

References

  1. Koukoulioti E, Fischer J, Schott E, et al. Association of HLA-DPA1 and HLA-DPB1 polymorphisms with spontaneous HBsAg seroclearance in Caucasians [published online November 24, 2018]. Liver Int. doi:10.1111/liv.14008
  2. Ganem D, Prince AM. Hepatitis B virus infection — natural history and clinical consequences. N Engl J Med. 2004;350(11):1118-1129.
  3. Liu F, Wang XW, Chen L, Hu P, Ren H, Hu HD. Systematic review with meta-analysis: development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis B surface antigen seroclearance. Aliment Pharmacol Ther. 2016;43(12):1253-1261.
  4. Kamatani Y, Wattanapokayakit S, Ochi H, et al. A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nat Genet. 2009;41(5):591-595.
  5. An P, Winkler C, Guan L, O'Brien SJ, Zeng Z HBV Study Consortium. A common HLA-DPA1 variant is a major determinant of hepatitis B virus clearance in Han Chinese. J Infect Dis. 2011;203(7):943-947.
  6. Wang L, Wu XP, Zhang W, et al. Evaluation of genetic susceptibility loci for chronic hepatitis B in Chinese: two independent case-control studies. PLoS One. 2011;6(3):e17608.
  7. Li J, Yang D, He Y, et al. Associations of HLA-DP variants with hepatitis B virus infection in southern and northern Han Chinese populations: a multicenter case-control study. PloS One. 2011;6(8):e24221.
  8. Guo X, Zhang Y, Li J, et al. Strong influence of human leukocyte antigen (HLA)-DP gene variants on development of persistent chronic hepatitis B virus carriers in the Han Chinese population. Hepatol. 2011;53(2):422-428.
  9. Nishida N, Sawai H, Matsuura K, et al. Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean. PloS One. 2012;7(6):e39175.
  10. Hu L, Zhai X, Liu J, et al. Genetic variants in human leukocyte antigen/DP-DQ influence both hepatitis B virus clearance and hepatocellular carcinoma development. Hepatol. 2012;55(5):1426-1431.
  11. Yan Z, Tan S, Dan Y, Sun X, Deng G, Wang Y. Relationship between HLA-DP gene polymorphisms and clearance of chronic hepatitis B virus infections: case-control study and meta-analysis. Infect Genet Evol. 2012;12(6):1222-1228.
  12. Wong DK, Watanabe T, Tanaka Y, et al. Role of HLA-DP polymorphisms on chronicity and disease activity of hepatitis B infection in Southern Chinese. PLoS One. 2013;8(6):e66920.
  13. Seto WK, Wong DK, Kopaniszen M, et al. HLA-DP and IL28B polymorphisms: influence of host genome on hepatitis B surface antigen seroclearance in chronic hepatitis B. Clin Infect Dis. 2013;56(12):1695-1703.
  14. Posuwan N, Payungporn S, Tangkijvanich P, et al. Genetic association of human leukocyte antigens with chronicity or resolution of hepatitis B infection in thai population. PLoS One. 2014;9(1):e86007.
  15. Thomas R, Thio CL, Apps R, et al. A novel variant marking HLA-DP expression levels predicts recovery from hepatitis B virus infection. J Virol. 2012;86(12):6979-6985.
  16. Vermehren J, Lotsch J, Susser S, et al. A common HLA-DPA1 variant is associated with hepatitis B virus infection but fails to distinguish active from inactive Caucasian carriers. PLoS One. 2012;7(3):e32605.
  17. Al-Qahtani AA, Al-Anazi MR, Abdo AA, et al. Association between HLA variations and chronic hepatitis B virus infection in Saudi Arabian patients. PLoS One. 2014;9(1):e80445.
  18. Akgollu E, Bilgin R, Akkiz H, et al. Association between chronic hepatitis B virus infection and HLA-DP gene polymorphisms in the Turkish population. Virus Res. 2017;232:6-12.
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