Host genetic background affects the course of infection and treatment response in patients with chronic hepatitis B.

Background: Hepatitis B virus (HBV) utilizes proteins encoded by the host to infect hepatocytes and replicate. Recently, several novel host factors have been identified and described as important to the HBV lifecycle. The influence of host genetic background on chronic hepatitis B (CHB) pathogenesis is still poorly understood.

Objectives: Here, we aimed to investigate the association of NTCP, FXRα, HNF1α, HNF4α, and TDP2 genetic polymorphisms with the natural course of CHB and antiviral treatment response.

Study Design: We genotyped 18 single-nucleotide polymorphisms using MALDI-TOF mass spectrometry in 136 patients with CHB and 100 healthy individuals. We investigated associations of the selected polymorphisms with biochemical, serological and hepatic markers of disease progression and treatment response.

Results: No significant differences in genotypic or allelic distribution between CHB and control groups were observed. Within TDP2, rs3087943 variations were associated with treatment response, and rs1047782 modified the risk of advanced liver inflammation. Rs7154439 within NTCP was associated with HBeAg seroconversion after 48 weeks of nucleos(t)ide analogue treatment. HNF1α genotypes were associated with treatment response, liver damage and baseline HBeAg presence. HNF4α rs1800961 predicted PEG-IFNα treatment-induced HBsAg clearance in long-term follow up.

Conclusions: This study indicates host genetic background relevance in the course of CHB and confirms the role of recently described genes for HBV infection. The obtained results might serve as a starting point for validation studies on the clinical application of selected genetic variants to predict individual risks of CHB-induced liver failure and treatment response.