Renin-angiotensin System Inhibitors and Development of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis

Background: There are controversial results available about using angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) and the development of cancers or improvement of clinical outcomes. Studies reported that using ACEI/ARB may enhance the development of hepatocellular carcinoma (HCC) and clinical outcomes. Objective: This meta-analysis aimed to assess the relationship between ACEI/ARB therapy and the development of HCC. Methods: PubMed, EMBASE and the Cochrane library were reviewed to identify clinical studies investigating the association between ACEI/ARB therapy and the risk of HCC development. The pooled risk ratio (RR) with 95% confidence intervals collected for the association between using ACEIs/ARBs and HCC development. Results: Patients with HCC benefit from the treatment with both ACEIs and ARBs (RR 0.704, 95% CI 0.526- 0.944, p = 0.019). However, only using ARBs was related to HCC risk (0.545 95% CI 0.470-0.632, P<0.0001). Moreover, the study types were significantly related to the observed effects of using both ARBs and ACEIs. Only cohort studies were significantly related to achieving better results (RR=0.513, 95% CI= 0.442-0.597, P<0.0001). Conclusion: Despite the small number and heterogeneity of the studies evaluating the relationship between treatment with ARBs and ACEIs and the development of HCC, our meta-analysis demonstrates that they may reduce the risk of HCC.