Ka Shing Cheung1,2, Lung Yi Mak1, Lok Ka Lam1, James Fung1,3, Fen Liu4, Wai Kay Seto5,6,7, Man Fung Yuen8,9. 1. Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. 2. Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. 3. State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China. 4. Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. 5. Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. wkseto@hkucc.hku.hk. 6. Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. wkseto@hkucc.hku.hk. 7. State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China. wkseto@hkucc.hku.hk. 8. Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. mfyuen@hkucc.hku.hk. 9. State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China. mfyuen@hkucc.hku.hk.
Abstract
INTRODUCTION: We aimed to describe long-term clinical outcomes in chronic hepatitis B (CHB) patients after HBsAg seroclearance, and identify factors that modify disease outcomes. METHODS: CHB patients with HBsAg seroclearance occurring between 1986 and 2017 were recruited. Primary outcome was cirrhosis/hepatocellular carcinoma (HCC), and secondary outcomes were hepatic decompensation, liver-related death/transplantation, and all-cause mortality. Multivariable Cox model included demographics, prior antivirals, comorbidities, drugs (statins, metformin, proton-pump inhibitors, non-selective beta-blockers), and laboratory parameters (platelet, liver function test, prothrombin time, alpha-fetoprotein [AFP], anti-HBs). Statin users were propensity score matched (PSM) with non-users (1:2 ratio) for survival analysis of all outcomes. RESULTS: Of 913 patients with HBsAg seroclearance (male: 613 [67.1%]; median age: 53.4 years [18.5-87.0]), 129 (14.1%) were statin users. During median follow-up of 7.7 years (up to 29.1 years), 64/833 (7.7%) developed cirrhosis, 25/905 (2.8%) developed HCC, 3/913 (0.3%) underwent transplantation, and 76/913 (8.3%) died. Statins were associated with lower cirrhosis/HCC risk (adjusted hazard ratio [aHR]: 0.44; 95% CI 0.20-0.96; aHR for every 1-year increase in use: 0.85; 95% CI 0.75-0.97). Statin users had no hepatic decompensation or liver-related death/transplantation (vs 18/778 [2.3%] and 18/784 [2.3%] cases in statin non-users, respectively). Statins were also associated with lower all-cause mortality risk (aHR: 0.21; 95% CI 0.08-0.53). PSM yields consistent results for beneficial effects of statins (log-rank p < 0.05 for all outcomes). Other factors for cirrhosis/HCC included increasing age (aHR: 1.06), diabetes (aHR: 2.03), higher creatinine (aHR: 1.008), GGT > 50U/L (aHR: 3.25), and AFP > 9 ng/mL (aHR: 10.14). CONCLUSION: Patients with HBsAg seroclearance have favorable long-term survival. However, liver-related adverse outcomes still develop, necessitating further investigations on beneficial effects of statins.
INTRODUCTION: We aimed to describe long-term clinical outcomes in chronic hepatitis B (CHB) patients after HBsAg seroclearance, and identify factors that modify disease outcomes. METHODS: CHB patients with HBsAg seroclearance occurring between 1986 and 2017 were recruited. Primary outcome was cirrhosis/hepatocellular carcinoma (HCC), and secondary outcomes were hepatic decompensation, liver-related death/transplantation, and all-cause mortality. Multivariable Cox model included demographics, prior antivirals, comorbidities, drugs (statins, metformin, proton-pump inhibitors, non-selective beta-blockers), and laboratory parameters (platelet, liver function test, prothrombin time, alpha-fetoprotein [AFP], anti-HBs). Statin users were propensity score matched (PSM) with non-users (1:2 ratio) for survival analysis of all outcomes. RESULTS: Of 913 patients with HBsAg seroclearance (male: 613 [67.1%]; median age: 53.4 years [18.5-87.0]), 129 (14.1%) were statin users. During median follow-up of 7.7 years (up to 29.1 years), 64/833 (7.7%) developed cirrhosis, 25/905 (2.8%) developed HCC, 3/913 (0.3%) underwent transplantation, and 76/913 (8.3%) died. Statins were associated with lower cirrhosis/HCC risk (adjusted hazard ratio [aHR]: 0.44; 95% CI 0.20-0.96; aHR for every 1-year increase in use: 0.85; 95% CI 0.75-0.97). Statin users had no hepatic decompensation or liver-related death/transplantation (vs 18/778 [2.3%] and 18/784 [2.3%] cases in statin non-users, respectively). Statins were also associated with lower all-cause mortality risk (aHR: 0.21; 95% CI 0.08-0.53). PSM yields consistent results for beneficial effects of statins (log-rank p < 0.05 for all outcomes). Other factors for cirrhosis/HCC included increasing age (aHR: 1.06), diabetes (aHR: 2.03), higher creatinine (aHR: 1.008), GGT > 50U/L (aHR: 3.25), and AFP > 9 ng/mL (aHR: 10.14). CONCLUSION:Patients with HBsAg seroclearance have favorable long-term survival. However, liver-related adverse outcomes still develop, necessitating further investigations on beneficial effects of statins.
Authors: Man-Fung Yuen; Wai-Kay Seto; Danny Hoi-Fan Chow; Kit Tsui; Danny Ka-Ho Wong; Vincent Wing-Shun Ngai; Benjamin Chun-Yu Wong; James Fung; John Chi-Hang Yuen; Ching-Lung Lai Journal: Antivir Ther Date: 2007