Highlights
- •Of 84,963 U.S. Veterans with cirrhosis, 8,558 (10.1%) were hospitalized with ACLF.
- •Binary statin exposure was associated with a 38% reduced hazard of developing ACLF.
- •Increasing dose exposure was associated with a progressively reduced hazard of ACLF.
- •Statin-exposed patients with ACLF had more kidney and less liver or brain failures.
Backgrounds & Aims
There is a need to identify therapies that prevent the development of acute-on-chronic
liver failure (ACLF) in patients with cirrhosis. This study sought to evaluate the
association between statin exposure and the risk of developing ACLF in a large national
cohort of patients with cirrhosis.
Methods
We performed a retrospective cohort study of patients diagnosed with cirrhosis within
the Veterans Health Administration from 2008 and 2018. Patients were stratified into
3 groups based on statin exposure (statin naïve, existing statin user, and new statin
initiator). Cox proportional hazards regression models with inverse probability treatment
weighting and marginal structural models were utilized to comprehensively address
potential confounding in estimating the association between time-updated statin exposure
and first occurrence of high-grade ACLF.
Results
The cohort included 84,963 patients, of whom 26.9% were on a statin at baseline. A
total of 8,558 (10.1%) patients with cirrhosis were hospitalized with high-grade ACLF
over a median follow-up time of 51.6 months (IQR 27.5–81.4). Time-updated statin use
was associated with a significant reduction in the hazard of developing ACLF (hazard
ratio [HR] 0.62, 95% CI 0.59-0.65, p <0.001). Increasing doses of statin were associated with progressively reduced hazard
of developing ACLF (HR 0.75, 95% CI 0.66-0.86, p <0.001 for <20 mg vs. 0 mg of time-updated statin exposure, in simvastatin equivalents; HR 0.61, 95%, CI
0.58-0.64, p <0.001 for >20 mg vs. 0 mg statin exposure). Furthermore, every additional 5 months of statin exposure
was associated with a 9% reduced hazard of high-grade ACLF (HR 0.91, 95% CI 0.90-0.92,
p <0.001).
Conclusions
In this large, retrospective, cohort study in patients with cirrhosis, statin use
was significantly associated with reduced development of high-grade ACLF.
Lay summary
Statin therapy has been shown to have numerous beneficial effects in patients with
chronic liver disease. This study demonstrated a strong association between statin
therapy and a reduced risk of acute-on-chronic liver failure development in patients
with cirrhosis. The results of this study support the promising role that statins
may play in future prevention of acute-on-chronic liver failure in patients with cirrhosis.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: January 20, 2022
Accepted:
December 28,
2021
Received in revised form:
December 13,
2021
Received:
October 20,
2021
Footnotes
Author names in bold designate shared co-first authorship
Identification
Copyright
© 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
