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

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Background & Aims: Observational studies have shown an association between statin or aspirin use and a decreased risk of hepatocellular carcinoma (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 & Results: We specified target trials for statins and, separately, aspirin and emulated them using Danish healthcare 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 five years compared to not using statins resulted in relative risk (RR) 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, five years of continuous statin use resulted in a 33% relative risk reduction of HCC (number needed to treat = 94) and a 31% relative risk 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.
Translated title of the contributionEffekterne af statiner og hjertemagnyl på risikoen for hepatocellulært karcinom ved alkoholrelateret cirrose: landsdækkende emulerede forsøg
Original languageEnglish
JournalHepatology Communications
Publication statusAccepted/In press - 14 Oct 2022

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