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.