Do renin-angiotensin system inhibitors reduce risk for hepatocellular carcinoma?: A nationwide nested case-control study - 01/12/20

Doi : 10.1016/j.clinre.2020.07.015

Kwang Min Kim ^a, Ji Hye Roh ^b, Sangjin Lee ^c, Jeong-Hyun Yoon ^b,⁎
^a Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
^b College of Pharmacy, Pusan National University, Busan, South Korea
^c Department of Statistics, College of Natural Science, Pusan National University, Busan, South Korea

^⁎Corresponding author.

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Highlights

•	A much-debated question is whether renin-angiotensin system inhibitors (RASi) have any beneficial effects in patients with HCC.
•	The present study did not prove a significant association between RASi use and HCC across the entire cohort.
•	The results of this study indicate lower HCC incidence with RASi use in some subgroups.
•	The RASi use significantly reduced the risk of HCC incidence in women, but not in men.
•	Angiotensin II receptor blockers had the greatest impact on lowering the risk of HCC incidence, compared with other types of RASi.

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Summary

Background

To date, there has been a renewed interest in renin-angiotensin system inhibitors (RASi) for HCC prevention because they may reduce potent angiogenic factors.

Objectives

This study set out to investigate associations between RASi use and HCC development.

Methods

We conducted a nested case-control study. A case was defined as a patient who was newly diagnosed with HCC. We selected 567 cases and controls using 1:1 propensity score matching. RASi exposure was classified into ever-user and never-user, then categorized according to cumulative dose and prescription period. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for HCC incidence according to RASi use were analyzed.

Results

Overall, no significant association was found between exposure to RASi and HCC incidence (ever-user vs. never-user: aOR, 0.77; 95% CI, 0.56−1.07). In subgroup analysis, women receiving RASi ≥30 cumulative defined daily doses (cDDDs) showed significantly lower aORs (0.49; 95% CI, 0.24−0.95. Angiotensin II receptor blockers only-use ≥30 cDDD was significantly associated with reduced risk of HCC (aOR, 0.65; 95% CI, 0.43−0.97). In cases where subjects did not have diabetes mellitus and where the cDDD of RASi was 1800 or more, the risk of HCC development was significantly reduced compared to that in subjects with no RASi exposure (aOR, 0.26; 95% CI, 0.08−0.72).

Conclusion

The present study did not verify a significant overall association between RASi use and HCC but indicated lower HCC incidence in some subgroups. The possibility of a beneficial effect at a higher cumulative RASi dose was also presented.

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Keywords : Renin-angiotensin system inhibitors, Angiotensin II receptor blockers, Hepatocellular carcinoma, Defined daily doses, Nested case-control study