HLA Variations and Association with Complicated Chronic Hepatitis B Virus Infection: A Prospective Cohort Study

Author(s): Evangelia Myserli, Asimina Fylaktou, Konstantinos Ouranos, Maria Exindari, Polina Agorastou, Evangelia Sidira, Margarita Samali, Grigorios Myserlis, Ioannis Goulis, Georgia Gioula

Background:

Human leukocyte antigen (HLA) variations are associated with variable hepatitis B virus (HBV) infection course, including viral clearance or progression to complicated disease (cirrhosis or hepatocellular carcinoma [HCC]).

Methods:

We conducted a single-center prospective study including patients with either spontaneous clearance of hepatitis B surface antigen (HBsAg) (SC group) or progression to complicated HBV infection (ccHBV group). HLA alleles of patients with HBV clearance or complicated HBV infection, as well as that of healthy controls, were genotyped in low- and high-resolution analyses by single-specific primer polymerase chain reaction to identify genetic loci associated with variable disease course.

Results:

Our analysis included 101 individuals in the SC group and 24 individuals in the ccHBV group. Low-resolution HLA analysis revealed that the prevalence of the HLA-A*01 (23.91% in the ccHBV group vs. 11.11% in the SC group, P = 0.03, OR = 2.50, 95% CI [1.0- 5.98]) and HLA-B*57 (11.11% in the ccHBV group vs. 2.03% in the SC group, P = 0.01 < 0.05, OR = 5.82, 95% CI [1.2-30.68]) alleles were significantly higher in the ccHBV group compared to the SC group. Also, low-resolution analysis showed that the prevalence of the HLA-A*01 allele (23.91% in the ccHBV group vs. 9.7% in the control group, P = 0.004 < 0.05, OR = 2.93, 95% CI [1.34-5.9]) was significantly higher and that of the HLA-C*15 allele (8.1% in the control group vs. 0% in the ccHBV group, P = 0.04 < 0.05, OR = 2.85, 95% CI [0.5-16.16]) was significantly lower in the ccHBV compared to the control group Finally, high-resolution analysis showed that the prevalence of the HLA-DQB1*05:01 allele (13,64% in the ccHBV group vs. 13,16% in the control group, P = 0.02 < 0.05, OR = 2.82, 95% CI [1.17-6.33]) was significantly higher in the ccHBV compared to the control group.

Conclusion:

In this analysis, HLA allele variations were associated with varying risk for progression to complicated HBV infection. Future larger studies are required to validate the results and ascertain whether HLA gene variations could have prognostic and therapeutic implications.