TNF-α polymorphisms affect persistence and progression of HBV infection

Abstract

Background: Hepatitis B virus (HBV) infections are a major threat worldwide. Disease progression and outcome is diverse and depends on host genetic background. Recently, a high rate of HBV reactivation in individuals receiving tumor necrosis factor-α (TNF-α) antagonists showed the importance of this cytokine in HBV infection control. Here, we investigated the influence of TNF-α promoter polymorphisms on susceptibility to chronic HBV infection (CHB), liver injury progression and outcomes. Methods: A total of 231 patients with CHB constituted the study group and 100 healthy volunteers—the local control group. TNF-α −1031T/C, −863C/A, −857C/T, −308G/A, and −238G/A were genotyped using MALDI-TOF mass spectrometry. Results: TNF-α −1031C and −863A alleles were observed more frequently in CHB group than in healthy controls. Carriers of TNF-α −1031C and −863A variant alleles had lower baseline levels of serum HBV DNA and lower liver necroinflammatory activity than dominant homozygotes. A −857CT genotype predisposed to higher necroinflammatory activity. No associations between TNF-α variants and liver fibrosis were found. Conclusion: This study indicates that TNF-α −863A and −1031C alleles are associated with increased susceptibility to CHB in individuals from northern Poland. The same variants determine the course of CHB, lowering viremia and reducing necroinflammatory activity of the liver.