Elsevier

Journal of Clinical Virology

Volume 120, November 2019, Pages 1-5
Journal of Clinical Virology

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

https://doi.org/10.1016/j.jcv.2019.09.002Get rights and content

Highlights

  • Genetic diversity within NTCP, HNF1α, TDP2 has an impact on treatment responseand liver condition.

  • TDP2 and HNF1α polymorphism is associated with HBsAg seroclearance and liver fibrosis.

  • NTCP and HNF1α polymorphisms influence on HBeAg/anti-HBe presence.

  • Our study provided evidence for the importance of recently described genes in HBV pathogenesis.

  • Identified SNPs may serve as biomarkers of disease progression, individual’s risk of developing liver injury and/or treatment response.

Abstract

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.

Section snippets

Background

Chronic hepatitis B virus (HBV) infection is present in more than 350 million people worldwide [1], and might progress to fibrosis, cirrhosis or hepatocellular carcinoma [2]. Evaluation of liver damage by needle biopsy or non-invasive methods, such as elastography, is crucial to estimating chronic liver disease outcomes.

Covalently closed circular (ccc) DNA, a reservoir and episomal form of the HBV genome, cannot be efficiently eradicated with current treatment options, including pegylated

Objectives

The aim of this study was to investigate the influence of host genetic background within the NTCP, FXRα, HNF1α, HNF4α, and TDP2 genes on treatment response and liver fibrosis progression in patients with chronic hepatitis B (CHB).

Patients

The study group included 136 patients with CHB who were admitted to the Department of Infectious Diseases, Medical University of Gdansk, and the Hepatology Outpatients Clinic Pomeranian Centre for Infectious Diseases and Tuberculosis in Gdansk in 2014-2016. Chronicity was defined as persistence of hepatitis B surface antigen (HBsAg) and anti-HBc antibodies (IgG type) for at least 24 months prior to enrolment. Blood tests, including alanine aminotransferase (ALT) activity, HBsAg, HBeAg,

Study group characteristics

The study group constituted 136 patients with CHB, whereas the control group included 100 healthy volunteers. Baseline characteristics of the enrolled individuals are shown in Table 1. Patients treated with NA were significantly older and had higher levels of HBV DNA, ALT, and liver fibrosis stage than the patients treated with PEG-IFNα. HBeAg-positivity was more frequent in NA-treated than in PEG-IFNα-treated patients. Out of 136 treated patients, 12 (9%) became HBsAg-negative after treatment,

Discussion

Recently, a few novel genes that seem to be crucial for HBV infection and viral lifecycle have been described: NTCP [4], which is responsible for HBV attachment to hepatocytes, FXRα, which regulates the expression of NTCP [10], and TDP2, which is involved in viral cccDNA formation [18]. In this study, we showed that common polymorphic changes in host genes recently associated with HBV infection, TDP2 and NTCP, affect the course of CHB, particularly treatment response and in the case of TDP2,

Declaration of Interest

None.

Acknowledgements

This work was financed by the National Centre for Research and Development (NCBR), grant no. INFECT-ERA/01/2014 and ST79 from the Medical University of Gdansk, and the MOBI4Health project, which is funded from the European Union’s Seventh Framework Programme under Grant Agreement no. 316094.

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