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

Abstract

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.