Fan Li1, Xiaodong Li2, Tao Yan3, Yan Liu4, Yongqian Cheng3, Zhihui Xu2, Qing Shao1, Hao Liao2, Pengyu Huang2, Jin Li2, Guo-Feng Chen5, Dongping Xu6,7. 1. The Second Liver Cirrhosis Diagnosis and Treatment Center, Beijing 302 Hospital, 100 Middle Street of 4th Ring Road, Beijing, 100039, China. 2. Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, 100 Middle Street of 4th Ring Road, Beijing, 100039, China. 3. International Liver Diseases Diagnosis and Treatment Center, Beijing 302 Hospital, Beijing, 100039, China. 4. Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, 100039, China. 5. The Second Liver Cirrhosis Diagnosis and Treatment Center, Beijing 302 Hospital, 100 Middle Street of 4th Ring Road, Beijing, 100039, China. bjchen302@gmail.com. 6. Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, 100 Middle Street of 4th Ring Road, Beijing, 100039, China. xudongping302@sina.com. 7. Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, 100039, China. xudongping302@sina.com.
Abstract
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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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. METHODS: 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. RESULTS: 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. CONCLUSIONS:HBV preS deletion is positively associated with liver fibrosis progression in chronic HBV-infectedpatients. HBV preS2 deletion may serve as a warning indicator for liver fibrosis progression.
Authors: S K Sarin; M Kumar; G K Lau; Z Abbas; H L Y Chan; C J Chen; D S Chen; H L Chen; P J Chen; R N Chien; A K Dokmeci; Ed Gane; J L Hou; W Jafri; J Jia; J H Kim; C L Lai; H C Lee; S G Lim; C J Liu; S Locarnini; M Al Mahtab; R Mohamed; M Omata; J Park; T Piratvisuth; B C Sharma; J Sollano; F S Wang; L Wei; M F Yuen; S S Zheng; J H Kao Journal: Hepatol Int Date: 2015-11-13 Impact factor: 6.047