Evolutionary Analysis of Pre-S/S Mutations in HBeAg-Negative Chronic Hepatitis B With HBsAg < 100 IU/ml

Frontiers in Public Health

article

Yingping Wu¹  Zhiqiang Zhu¹  Jianyong Wu¹  Wenzi Bi¹  Wei Xu¹  Xiaoping Xia¹  Dongsheng Han² 

[1] Department of Clinical Laboratory, Fourth Affiliated Hospital of Zhejiang University School of Medicine;Clinical Medical Examination Center, Northern Jiangsu People's Hospital

关键词: inactive HBsAg carrier;    reactivation phase;    genome diversity;    pre-S/S region mutation;    selective pressure;   

DOI  :  10.3389/fpubh.2021.633792

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background: Hepatitis B surface antigen (HBsAg) and viral load are important clinical indicators for antiviral therapy. Few studies have evaluated viral sequence biomarkers predicting the risk of hepatocellular carcinoma (HCC) in the stage, which show a low serological response (HBsAg 2,000 IU/ml). This study aims to determine the trend of the biological prevalence within the pre-S/S regions of special model of inactive CHB infection. Methods: We used Sanger sequencing, quantitative HBV serology (HBeAg and HBsAg), and liver function index to identify whether HBV genome sequences are associated with long-term risk of further HCC progression in special inactive CHB infection. Results: HBV sequencing analysis of 28 CHB patients with special infectious pattern showed higher genetic diversity among four opening reading frames (ORFs) ( p < 0.001). However, dN/dS ratios of HBsAg and pre-C/C regions in the experimental group showed no significantly different from those in the HCC group ( p = 0.06), while significantly lower in polymerase and HBxAg regions of the experimental group ( p < 0.001). In addition, seven positively selected sites were identified in pre-S1, five in pre-S2, and four in S, in which five sites (128H/135Q/135R/139L/141P) were among “α” determinant. Conclusions: These mutations in the pre-S/S region might be associated with the HCC phenotype of low HBsAg expression, with the P region possibly impacting high viral loads. Increased viral diversity across the HBV genome is also associated with low levels of HBsAg. The cumulative evolutionary changes in the HBV pre-S/S regions shows that facilitate immune evasion should be monitored individually. Due to the similarity of evolutionary characteristics in HCC, low serological responses and high viremia may be associated with the risk of further disease progression.

【 授权许可】

CC BY