TY - JOUR
T1 - Effects of statins and aspirin on HCC risk in alcohol-related cirrhosis
T2 - nationwide emulated trials
AU - Kraglund, Frederik
AU - Christensen, Diana H.
AU - Eiset, Andreas H.
AU - Villadsen, Gerda E.
AU - West, Joe
AU - Jepsen, Peter
N1 - Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of the American Association for the Study of Liver Diseases.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - Aspirin/therapeutic use
KW - Carcinoma, Hepatocellular/epidemiology
KW - Fibrosis
KW - Humans
KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
KW - Liver Cirrhosis, Alcoholic
KW - Liver Cirrhosis/complications
KW - Liver Neoplasms/epidemiology
UR - http://www.scopus.com/inward/record.url?scp=85149309233&partnerID=8YFLogxK
U2 - 10.1097/HC9.0000000000000013
DO - 10.1097/HC9.0000000000000013
M3 - Journal article
C2 - 36633465
AN - SCOPUS:85149309233
SN - 2471-254X
VL - 7
JO - Hepatology Communications
JF - Hepatology Communications
IS - 1
M1 - e0013
ER -