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Review
. 2023 Mar;57(6):600-609.
doi: 10.1111/apt.17371. Epub 2023 Jan 10.

Meta-analysis: Chemoprevention of hepatocellular carcinoma with statins, aspirin and metformin

Rebecca W Zeng  1 , Jie Ning Yong  1 , Darren J H Tan  1 , Clarissa E Fu  1 , Wen Hui Lim  1 , Jieling Xiao  1 , Kai En Chan  1 , Caitlyn Tan  1 , Xin Lei Goh  1 , Douglas Chee  2 , Nicholas Syn  1 , Eunice X Tan  1   2   3 , Mark D Muthiah  1   2   3 , Cheng Han Ng  1 , Nobuharu Tamaki  4 , Sung Won Lee  5   6 , Beom Kyung Kim  7   8 , Mindie H Nguyen  9 , Rohit Loomba  10 , Daniel Q Huang  1   2   3   10
Affiliations
Review

Meta-analysis: Chemoprevention of hepatocellular carcinoma with statins, aspirin and metformin

Rebecca W Zeng et al. Aliment Pharmacol Ther. 2023 Mar.

Abstract

Background: Emerging data suggest that statins, aspirin and metformin may protect against hepatocellular carcinoma (HCC) development. However, prior meta-analyses were limited by heterogeneity and inclusion of studies without adequate adjustment for baseline risks.

Aim: To examine by an updated meta-analysis the association between these medications and HCC risk.

Methods: Medline and Embase databases were searched from inception to March 2022 for studies that balanced baseline risks between study groups via propensity score matching or inverse probability of treatment weighting, that reported the impact of statins, aspirin or metformin on HCC risk. Multivariable-adjusted hazard ratios (HRs) for HCC were pooled using a random effects model.

Results: Statin use was associated with reduced HCC risk overall (HR: 0.52; 95% CI: 0.37-0.72) (10 studies, 1,774,476), and in subgroup analyses for cirrhosis, hepatitis B/C, non-alcoholic fatty liver disease, studies accounting for concurrent aspirin and metformin consumption and lipophilic statins. Aspirin use was associated with reduced HCC risk overall (HR: 0.48; 95% CI: 0.27-0.87) (11 studies, 2,190,285 patients) but not in studies accounting for concurrent statin and metformin use. Metformin use was not associated with reduced HCC risk overall (HR: 0.57; 95% CI: 0.31-1.06) (3 studies, 125,458 patients). Most analyses had moderate/substantial heterogeneity, except in follow-up <60 months for aspirin (I2 = 0%).

Conclusion: Although statin and aspirin use were associated with reduced HCC risk, only statin use was significant in subgroup analyses accounting for concurrent medications. Metformin use was not associated with reduced HCC risk. These data have implications for future clinical trial design.

Keywords: hepatoma; incidence; liver cancer; prevention.

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Conflict of interest statement

MHN: Research support: Pfizer, Enanta, Gilead, Exact Sciences, Vir Biotech, Helio Health, National Cancer Institute, Glycotest, B.K. Kee Foundation. Consulting and/or Advisory Board: Intercept, Exact Science, Gilead, GSK, Eli Lilly, Laboratory of Advanced Medicine, Janssen. R.L. receives funding support from NIAAA (U01AA029019), NIEHS (5P42ES010337), NCATS (5UL1TR001442), NIDDK (U01DK130190, U01DK061734, R01DK106419, P30DK120515, R01DK121378, R01DK124318), NHLBI (P01HL147835) and DOD PRCRP (W81XWH-18-2-0026). RL serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals and Viking Therapeutics. In addition, his institutions received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Merck, Pfizer, Sonic Incytes and Terns Pharmaceuticals. Co-founder of LipoNexus Inc. D.H. receives funding support from Singapore Ministry of Health’s National Medical Research Council under its NMRC Research Training Fellowship (MOH-000595-01). In addition, he has served as an advisory board member for Eisai. The other authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
PRISMA flowchart.
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