Yameng Sun1, Xiaoning Wu1, Jialing Zhou1, Tongtong Meng1, Bingqiong Wang1, Shuyan Chen1, Hui Liu2, Tailing Wang3, Xinyan Zhao1, Shanshan Wu1, Yuanyuan Kong1, Xiaojuan Ou1, Aileen Wee4, Neil D Theise5, Chao Qiu6, Wenhong Zhang6, Fengmin Lu7, Jidong Jia8, Hong You9. 1. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China. 2. Department of Pathology, Beijing You-an Hospital, Capital Medical University, Beijing, China. 3. Department of Pathology, China-Japan Friendship Hospital, Beijing, China. 4. Department of Pathology, National University Hospital, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 5. Department of Pathology, New York University School of Medicine, New York, New York. 6. Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. 7. State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. 8. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China. Electronic address: jia_jd@ccmu.edu.cn. 9. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China. Electronic address: youhong30@sina.com.
Abstract
BACKGROUND & AIMS: Progression of liver fibrosis still occurs in some patients with chronic hepatitis B virus (HBV) infection despite antiviral therapy. We aimed to identify risk factors for fibrosis progression in patients who received antiviral therapy. METHODS: We conducted a longitudinal study of patients with chronic HBV infection and liver biopsies collected before and after 78 weeks of anti-HBV therapy. Fibrosis progression was defined as Ishak stage increase ≥ 1 or as predominantly progressive classified by P-I-R system (Beijing Classification). Levels of HBV DNA and HBV RNA in blood samples were measured by real-time quantitative PCR. HBV RNA in liver tissue was detected by in situ hybridization. RESULTS: A total of 239 patients with chronic HBV infection with paired liver biopsies were included. Among the 163 patients with significant fibrosis at baseline (Ishak ≥ stage 3), fibrosis progressed in 22 patients (13%), was indeterminate in 24 patients (15%), and regressed in 117 patients (72%). Univariate and multivariate analyses revealed that independent risk factors for fibrosis progression were higher rate of detected HBV DNA at week 78 (odds ratio, 4.84; 95% CI, 1.30-17.98; P = .019) and alcohol intake (odds ratio, 23.84; 95% CI, 2.68-212.50; P = .004). HBV DNA was detected in blood samples from a significantly higher proportion of patients with fibrosis progression (50%) at week 78 than patients with fibrosis regression (19%) or indeterminate fibrosis (26%) (P = .015), despite low viremia (20-200 IU/mL) in all groups. The decrease of serum HBV RNA from baseline in the fibrosis regression group was larger than that in the fibrosis progression group. CONCLUSIONS: In a longitudinal study of patients with chronic HBV infection, we associated liver fibrosis progression at week 78 of treatment with higher rates of detected HBV DNA. We propose that a low level of residual HBV may still promote fibrosis progression, and that patients' levels of HBV DNA should be carefully monitored.
BACKGROUND & AIMS: Progression of liver fibrosis still occurs in some patients with chronic hepatitis B virus (HBV) infection despite antiviral therapy. We aimed to identify risk factors for fibrosis progression in patients who received antiviral therapy. METHODS: We conducted a longitudinal study of patients with chronic HBV infection and liver biopsies collected before and after 78 weeks of anti-HBV therapy. Fibrosis progression was defined as Ishak stage increase ≥ 1 or as predominantly progressive classified by P-I-R system (Beijing Classification). Levels of HBV DNA and HBV RNA in blood samples were measured by real-time quantitative PCR. HBV RNA in liver tissue was detected by in situ hybridization. RESULTS: A total of 239 patients with chronic HBV infection with paired liver biopsies were included. Among the 163 patients with significant fibrosis at baseline (Ishak ≥ stage 3), fibrosis progressed in 22 patients (13%), was indeterminate in 24 patients (15%), and regressed in 117 patients (72%). Univariate and multivariate analyses revealed that independent risk factors for fibrosis progression were higher rate of detected HBV DNA at week 78 (odds ratio, 4.84; 95% CI, 1.30-17.98; P = .019) and alcohol intake (odds ratio, 23.84; 95% CI, 2.68-212.50; P = .004). HBV DNA was detected in blood samples from a significantly higher proportion of patients with fibrosis progression (50%) at week 78 than patients with fibrosis regression (19%) or indeterminate fibrosis (26%) (P = .015), despite low viremia (20-200 IU/mL) in all groups. The decrease of serum HBV RNA from baseline in the fibrosis regression group was larger than that in the fibrosis progression group. CONCLUSIONS: In a longitudinal study of patients with chronic HBV infection, we associated liver fibrosis progression at week 78 of treatment with higher rates of detected HBV DNA. We propose that a low level of residual HBV may still promote fibrosis progression, and that patients' levels of HBV DNA should be carefully monitored.
Authors: Calvin Q Pan; Nezam H Afdhal; Victor Ankoma-Sey; Ho Bae; Michael P Curry; Douglas Dieterich; Lynn Frazier; Andrew Frick; Hie-Won Hann; W Ray Kim; Paul Kwo; Scott Milligan; Myron J Tong; K Rajender Reddy Journal: Hepatol Commun Date: 2022-04-21