The preS deletion of hepatitis B virus (HBV) is associated with liver fibrosis progression in patients with chronic HBV infection
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Background and aims
Limited data are available regarding the association of hepatitis B virus (HBV) mutations with liver fibrosis in HBV infection. The study aimed to clarify whether HBV preS deletion mutation is associated with liver fibrosis progression.
A total of 469 patients were enrolled, including 324 with chronic hepatitis B (CHB), 28 with HBV-related compensated liver cirrhosis (LC), and 117 with HBV-related decompensated LC. All CHB and compensated LC patients received liver biopsy. Fibrosis grade was assessed using METAVIR score. HBV preS deletion was determined by direct sequencing and verified by clonal sequencing.
Overall preS deletion was detected in 12.6% (59/469) patients, specifically, in 7.51% (13/173), 10.60% (16/151), and 20.69% (30/145) of patients with no-to-mild liver fibrosis (F0–1), moderate-to-severe liver fibrosis (F2–3), and cirrhosis (F4), respectively (p < 0.01). Patients with preS-deleted HBV had lower serum HBV DNA and albumin levels compared to patients with wild-type HBV. The median length of preS deletion was 39-base pairs (bp) (3–204 bp) and the deletion most frequently emerged in preS2 initial region. Multivariate analysis identified the preS2 deletion rather than preS1 deletion to be an independent risk factor of significant fibrosis, i.e., METAVIR F ≥ 2 (p = 0.007). In addition, preS-deleted viral sequences were detected in the pool of intrahepatic HBV covalently closed circular DNA.
HBV preS deletion is positively associated with liver fibrosis progression in chronic HBV-infected patients. HBV preS2 deletion may serve as a warning indicator for liver fibrosis progression.
KeywordsHepatitis B virus preS deletion Liver fibrosis Covalently closed circular DNA
Covalently closed circular DNA
Chronic hepatitis B
Decompensated liver cirrhosis
Histological activity index
Hepatitis B e antigen
Hepatitis B virus
Liver stiffness measurement
Na+/sodium taurocholate cotransporting polypeptide
Prothrombin time-international normalized ratio
This study was supported by grants from the National Natural Science Foundation of China (Nos. 81572010 and 81373136), and Application Research of Capital Clinical Characteristic and Promotion of Achievements (Z151100004015011), the National Thirteenth Five-Year Special Grand Project for Infectious Diseases (No. 2017ZX10302201-001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Compliance with ethical standards
Conflict of interest
Fan Li, Xiaodong Li, Tao Yan, Yan Liu, Yongqian Cheng, Zhihui Xu, Qing Shao, Hao Liao, Pengyu Huang, Jin Li, Guo-Feng Chen, and Dongping Xu have declared that no competing interests exist.
This study was approved by the Ethics Committee of Beijing 302 Hospital. All patients provided their informed consent for the use of their samples for research before enrollment in the Database of Beijing 302 Hospital.
Data sharing statement
Technical appendix, statistical code, and data set are available upon request of the corresponding author Dongping Xu (xudongping302@ sina.com). The information of HBV genetic sequences with preS deletion is freely available from GenBank (KX534108-KX534166). Raw data are available from the Ethics Committee of the Beijing 302 Hospital (Beijing, China) for researchers who meet the criteria for access to confidential database.
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