Statin Use and Risk of Cirrhosis and Related Complications in Patients With Chronic Liver Diseases: A Systematic Review and Meta-analysis

doi:10.1016/j.cgh.2017.04.039

Clinical Gastroenterology and Hepatology

Volume 15, Issue 10, October 2017, Pages 1521-1530.e8

https://doi.org/10.1016/j.cgh.2017.04.039 Get rights and content

Background & Aims

Statins have been variably shown to decrease risk and complications of chronic liver diseases (CLDs). We performed a systematic review and meta-analysis to evaluate the association between statins and risk of cirrhosis and related complications in patients with CLDs.

Methods

Through a systematic literature search up to March 2017, we identified 13 studies (3 randomized trials, 10 cohort studies) in adults with CLDs, reporting the association between statin use and risk of development of cirrhosis, decompensated cirrhosis, improvements in portal hypertension, or mortality. Pooled relative risk (RR) estimates with 95% confidence interval (CIs) were calculated using random effects model. Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess quality of evidence.

Results

Among 121,058 patients with CLDs (84.5% with hepatitis C), 46% were exposed to statins. In patients with cirrhosis, statin use was associated with 46% lower risk of hepatic decompensation (4 studies; RR, 0.54; 95% CI, 0.46–0.62; I₂ = 0%; moderate-quality evidence), and 46% lower mortality (5 studies; RR, 0.54; 95% CI, 0.47–0.61; I₂ = 10%; moderate-quality evidence). In patients with CLD without cirrhosis, statin use was associated with a nonsignificant (58% lower) risk of development of cirrhosis or fibrosis progression (5 studies; RR, 0.42; 95% CI, 0.16–1.11; I₂ = 99%; very-low-quality evidence). In 3 randomized controlled trials, statin use was associated with 27% lower risk of variceal bleeding or progression of portal hypertension (hazard ratio, 0.73; 95% CI, 0.59–0.91; I₂ = 0%; moderate-quality evidence).

Conclusions

Based on a systematic review and meta-analysis, statin use is probably associated with lower risk of hepatic decompensation and mortality, and might reduce portal hypertension, in patients with CLDs. Prospective observational studies and randomized controlled trials are needed to confirm this observation.

Section snippets

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,⁴⁴ using an a priori established protocol.

Search Results

Of the 1706 unique studies identified using our search criteria, 13 studies met our inclusion criteria and were included in our meta-analysis (3 RCTs and 10 observational studies).33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 50, 51 Six studies included participants with noncirrhotic CLDs,35, 39, 40, 41, 42, 43 6 studies included participants with compensated cirrhosis,36, 37, 42, 43, 50, 51 and 3 studies included individuals with decompensated cirrhosis.33, 34, 38 One study was excluded because

Discussion

In this systematic review and meta-analysis of 13 studies on the association between statins and risk of clinically relevant outcomes in 121,058 patients with CLDs, we made several key observations. First, moderate-quality evidence supports the use of statins for decreasing the risk of hepatic decompensation by 46% especially in patients with baseline compensated cirrhosis, although there is very low confidence in estimates supporting the use of statins to decrease risk of fibrosis progression

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: This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e158. Learning Objective–Upon completion of this activity, successful learners will be able to identify the potential benefits of statin use in chronic liver disease.

: Conflicts of interest The authors disclose no conflicts.

: Funding Rohit Loomba is supported in part by the American Gastroenterological Association Foundation – Sucampo – ASP Designated Research Award in Geriatric Gastroenterology, by a T. Franklin Williams Scholarship Award, and grants K23-DK090303 and R01-DK106419-03. Siddharth Singh is supported by the National Institutes of Health/National Library of Medicine training grant T15LM011271. Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number P42ES010337.

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Systematic reviews and meta-analysesStatin Use and Risk of Cirrhosis and Related Complications in Patients With Chronic Liver Diseases: A Systematic Review and Meta-analysis

Background & Aims

Methods

Results

Conclusions

Section snippets

Methods

Search Results

Discussion

FEBS Lett

Atherosclerosis

Atherosclerosis

Int J Cardiol

Am Heart J

J Biol Chem

Gastroenterology

J Hepatol

J Hepatol

Gastroenterology

Value Health

Gastroenterology

Gastroenterology

Dig Liver Dis

J Hepatol

J Hepatol

J Hepatol

Control Clin Trials

J Clin Epidemiol

J Hepatol

Gastroenterology

Gastroenterology

Deaths: final data for 2013

National Vital Statistics Reports

HMG-CoA reductase inhibitors for treatment of hypercholesterolemia

N Engl J Med

Treatment of hypercholesterolemia with a HMG CoA reductase inhibitor (CS-500). I. Phase I study in normal subjects

Geriatr Med

Effects of an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase on serum lipoproteins and ubiquinone-10 levels in patients with familial hypercholesterolemia

N Engl J Med

Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in healthy volunteers

J Clin Invest

Therapeutic response to lovastatin (mevinolin) in nonfamilial hypercholesterolemia: a multicenter study

JAMA

Systematic reviews and meta-analyses
Statin Use and Risk of Cirrhosis and Related Complications in Patients With Chronic Liver Diseases: A Systematic Review and Meta-analysis