TNF-α polymorphisms affect persistence and progression of HBV infection

Area of Science:

• Immunogenetics
• Hepatology
• Virology

Background:

• Hepatitis B virus (HBV) infection outcomes vary based on host genetics.
• Tumor necrosis factor-α (TNF-α) plays a role in controlling HBV infection, as evidenced by reactivation in patients on TNF-α antagonists.
• The influence of TNF-α genetic variations on chronic HBV (CHB) infection remains to be fully elucidated.

Purpose of the Study:

• To investigate the association between TNF-α promoter polymorphisms and susceptibility to CHB.
• To determine the impact of these polymorphisms on liver injury progression and disease outcomes in CHB patients.

Main Methods:

• Genotyping of 5 TNF-α promoter polymorphisms (-1031T/C, -863C/A, -857C/T, -308G/A, -238G/A) in 231 CHB patients and 100 healthy controls.
• Utilized MALDI-TOF mass spectrometry for precise genotyping.
• Analyzed the correlation between TNF-α variants and HBV DNA levels, liver necroinflammatory activity, and fibrosis.

Main Results:

• TNF-α -1031C and -863A alleles were more prevalent in the CHB group compared to healthy controls.
• Carriers of TNF-α -1031C and -863A alleles exhibited lower HBV DNA levels and reduced liver necroinflammatory activity.
• The TNF-α -857CT genotype was associated with increased necroinflammatory activity, while no link to liver fibrosis was observed.

Conclusions:

• Specific TNF-α promoter alleles (-863A and -1031C) are associated with increased susceptibility to CHB in a Polish population.
• These TNF-α variants appear to modulate CHB disease course by lowering viral load and reducing liver inflammation.