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.

中文翻译：

---

宿主的遗传背景会影响慢性乙型肝炎患者的感染过程和治疗反应。

背景技术乙型肝炎病毒（HBV）利用宿主编码的蛋白质感染肝细胞并复制。最近，已经鉴定出几种新颖的宿主因素，它们对HBV生命周期至关重要。宿主遗传背景对慢性乙型肝炎（CHB）发病机理的影响仍然知之甚少。目的在这里，我们旨在调查NTCP，FXRα，HNF1α，HNF4α和TDP2基因多态性与CHB的自然病程和抗病毒治疗反应之间的关联。研究设计我们使用MALDI-TOF质谱法对136例CHB患者和100例健康个体的18个单核苷酸多态性进行了基因分型。我们调查了选定的多态性与疾病进展和治疗反应的生化，血清学和肝脏标志物的关联。结果CHB与对照组之间在基因型或等位基因分布上没有显着差异。在TDP2中，rs3087943变异与治疗反应相关，而rs1047782改善了晚期肝炎的风险。NTCP内的Rs7154439与核苷酸（t）ide类似物治疗48周后的HBeAg血清转化有关。HNF1α基因型与治疗反应，肝损害和基线HBeAg存在有关。HNF4αrs1800961在长期随访中预测了PEG-IFNα治疗引起的HBsAg清除。结论这项研究表明了CHB过程中宿主的遗传背景相关性，并证实了最近描述的基因在HBV感染中的作用。