Karn Wijarnpreecha1, Fang Li2, Yang Xiang3, Xun Xu4, Cong Zhu4, Vahed Maroufy5, Qing Wang2, Wei Tao5, Yifang Dang2, Huy Anh Pham2, Yujia Zhou2, Jianfu Li2, Xinyuan Zhang2, Hua Xu2, C Burcin Taner1, Liu Yang1, Cui Tao2. 1. Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA. 2. School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA. 3. Peng Cheng Laboratory, Shenzhen, China. 4. Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA. 5. Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Abstract
BACKGROUND: Previous studies have demonstrated an association between nonselective beta-blockers (NSBBs) and lower risk of hepatocellular carcinoma (HCC) in cirrhosis. However, there has been no population-based study investigating the risk of HCC among cirrhotic patients treated using carvedilol. AIMS: To determine the risk of HCC among cirrhotic patients with NSBBs including carvedilol. METHODS: This retrospective cohort study utilised the Cerner Health Facts database in the United States from 2000 to 2017. Kaplan-Meier estimate, Cox proportional hazards regression, and propensity score matching (PSM) were used to test the HCC risk among the carvedilol, nadolol, and propranolol groups compared with no beta-blocker group. RESULTS: The final cohort comprised 107 428 eligible patients. The 100-month cumulative HCC incidence of NSBBs was significantly lower than the no beta-blocker group (carvedilol (11.24%) vs no beta-blocker (15.69%), nadolol (27.55%) vs no beta-blocker (32.11%), and propranolol (26.17%) vs no beta-blocker (28.84%) (P values < 0.0001). NSBBs were associated with a significantly lower risk of HCC (Hazard ratio: carvedilol 0.61 (95% CI 0.51-0.73), nadolol 0.74 (95% CI 0.63-0.87), propranolol 0.75 (95% CI 0.66-0.84) after PSM in the multivariate cox analysis. In subgroup analysis, NSBBs reduced the risk of HCC in cirrhosis with complications and non-alcoholic cirrhosis. CONCLUSIONS: NSBBs, including carvedilol, were associated with a significantly decreased risk of HCC in patients with cirrhosis when compared with no beta-blocker regardless of complications status. Future randomised-controlled studies comparing the incidence of HCC among NSBBs should elucidate which NSBB would be the best option to prevent HCC in cirrhosis.
BACKGROUND: Previous studies have demonstrated an association between nonselective beta-blockers (NSBBs) and lower risk of hepatocellular carcinoma (HCC) in cirrhosis. However, there has been no population-based study investigating the risk of HCC among cirrhotic patients treated using carvedilol. AIMS: To determine the risk of HCC among cirrhotic patients with NSBBs including carvedilol. METHODS: This retrospective cohort study utilised the Cerner Health Facts database in the United States from 2000 to 2017. Kaplan-Meier estimate, Cox proportional hazards regression, and propensity score matching (PSM) were used to test the HCC risk among the carvedilol, nadolol, and propranolol groups compared with no beta-blocker group. RESULTS: The final cohort comprised 107 428 eligible patients. The 100-month cumulative HCC incidence of NSBBs was significantly lower than the no beta-blocker group (carvedilol (11.24%) vs no beta-blocker (15.69%), nadolol (27.55%) vs no beta-blocker (32.11%), and propranolol (26.17%) vs no beta-blocker (28.84%) (P values < 0.0001). NSBBs were associated with a significantly lower risk of HCC (Hazard ratio: carvedilol 0.61 (95% CI 0.51-0.73), nadolol 0.74 (95% CI 0.63-0.87), propranolol 0.75 (95% CI 0.66-0.84) after PSM in the multivariate cox analysis. In subgroup analysis, NSBBs reduced the risk of HCC in cirrhosis with complications and non-alcoholic cirrhosis. CONCLUSIONS: NSBBs, including carvedilol, were associated with a significantly decreased risk of HCC in patients with cirrhosis when compared with no beta-blocker regardless of complications status. Future randomised-controlled studies comparing the incidence of HCC among NSBBs should elucidate which NSBB would be the best option to prevent HCC in cirrhosis.