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Effects of statins and aspirin on HCC risk in alcohol-related cirrhosis: nationwide emulated trials

Kraglund, Frederik; Christensen, Diana H.; Eiset, Andreas H.; Villadsen, Gerda E.; West, Joe; Jepsen, Peter

Effects of statins and aspirin on HCC risk in alcohol-related cirrhosis: nationwide emulated trials Thumbnail


Frederik Kraglund

Diana H. Christensen

Andreas H. Eiset

Gerda E. Villadsen

Professor of Epidemiology

Peter Jepsen


Background and Aims: Observational studies have shown an association between statin or aspirin use and a decreased risk of HCC, but the effects of a well-defined treatment strategy remain unknown. We emulated trials of the effects of continuous statin or aspirin use on HCC risk in patients with cirrhosis due to alcohol-related liver disease (ALD cirrhosis). Approach and Results: We specified target trials for statins and, separately, aspirin and emulated them using Danish health care registries. All eligible patients with ALD cirrhosis diagnosed in 2000-2018 were included in either an exposed or an unexposed arm. Patients were followed until HCC or death without HCC. The 5-year risk of HCC was estimated using marginal structural models with inverse probability weighting. Using statins continuously for 5 years compared with not using statins resulted in a relative risk (RR) of HCC of 0.67 (95% CI: 0.45-0.91). The RR of death without HCC was 0.69 (95% CI: 0.65-0.77). For aspirin, the RR was 1.05 (95% CI: 0.60-1.42) for HCC and 1.02 (95% CI: 0.95-1.09) for death without HCC. Conclusions: In patients with ALD cirrhosis, 5 years of continuous statin use resulted in a 33% RR reduction of HCC (number needed to treat = 94) and a 31% RR reduction of death without HCC (number needed to treat = 7). Such strong causal effects are implausible and best explained by uncontrollable confounding, highlighting the need for randomized trials. Aspirin use likely does not affect the risk of HCC or death without HCC.

Journal Article Type Article
Acceptance Date Oct 13, 2022
Online Publication Date Jan 1, 2023
Publication Date Jan 1, 2023
Deposit Date Jan 12, 2023
Publicly Available Date Jan 12, 2023
Journal Hepatology Communications
Electronic ISSN 2471-254X
Publisher Ovid Technologies (Wolters Kluwer Health)
Peer Reviewed Peer Reviewed
Volume 7
Issue 1
Article Number e0013
Keywords Hepatology
Public URL
Publisher URL


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