Effect of renin-angiotensin system inhibitor in incident cancer among chronic hepatitis B patients: An emulated target trial using a nationwide cohort

Background Although the renin-angiotensin system (RAS) has been reported to be associated with cancer development, the anticancer effects of RAS inhibitors (RASi) remain controversial. Objectives This study aimed to investigate the effect of RASi use on cancer incidence in chronic hepatitis B (CHB) patients. Design We designed a series of pragmatic trials for each week and followed the patients until the cancer diagnosis, death, or end of follow-up. Methods We analyzed CHB patients aged 40–84 years from the nationwide database between 2009 and 2017. We used 3:1 propensity score matching. Results Among 15,477 RASi non-users and 5263 RASi users, 2002 developed cancer. The adjusted hazard ratio (HR) for all cancer in RASi users was 0.89 [95% confidence interval (CI): 0.81–0.99]. The adjusted HR (95% CI) of hepatocellular carcinoma (HCC) and extrahepatic cancer were 0.79 (0.65–0.96) and 0.93 (0.82–1.04), respectively. When RASi was further divided, the adjusted HR (95% CI) for cancer of the angiotensin-converting enzyme inhibitor user and the angiotensin II receptor blocker user were 0.66 (0.50–0.87) and 0.93 (0.84–1.03), respectively. Conclusion RASi use was associated with a decreased incidence of all cancers, particularly HCC, in CHB patients, suggesting a chemopreventive effect of RASi in this population.