From the Journals

Statin use cuts risks in compensated cirrhosis

 

Key clinical point: Statin therapy was associated with a significantly lower risk of hepatic decompensation and death in patients with compensated cirrhosis.

Major finding: Statin therapy was associated with a 46% decrease in the risk of both hepatic decompensation and mortality (risk ratios, 0.54) and with a 27% drop in the risk of portal hypertension and variceal bleeding (RR, 0.73).

Data source: A systematic review and meta-analysis of 10 cohort studies and three randomized controlled trials (121,058 patients).

Disclosures: The reviewers acknowledged the American Gastroenterological Association Foundation, a T. Franklin Williams Scholarship Award, the National Institutes of Health, and the National Library of Medicine. They reported having no relevant conflicts of interest.

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Look for indications to justify statin use in CLD/cirrhosis

The main mechanism in the development of cirrhosis in patients with chronic liver disease (CLD) is increased hepatic fibrogenesis. The initial consequence of cirrhosis is portal hypertension, which is the main driver of decompensation (defined as the presence of ascites, variceal hemorrhage, or encephalopathy).

Dr. Guadalupe Garcia-Tsao
Portal hypertension initially results from an increase in intrahepatic resistance, which in turn results from distortion of liver vascular architecture (mostly due to fibrosis) and from intrahepatic vasoconstriction (mostly due to endothelial cell dysfunction).
Statins are widely used for reducing cholesterol levels and cardiovascular risk. However, statins ameliorate endothelial dysfunction and have additional antifibrotic, anti-inflammatory, and antithrombotic properties, all of them of potential benefit in preventing progression of CLD/cirrhosis. In fact, statins have been shown to reduce portal pressure in cirrhosis.

In a meta-analysis of 13 studies, Kim et al. demonstrated that statin use is associated with a 58% lower risk of developing cirrhosis/fibrosis progression in patients with CLD (not statistically significant), while in patients with compensated cirrhosis of any etiology, statin use was associated with a statistically significant 46% lower risk of developing decompensation and death.

Most studies in the meta-analysis were observational/retrospective. Although the authors jointly analyzed three randomized controlled trials, only one of the trials looked at clinical outcomes. This important double-blind, placebo-controlled study in patients with recent variceal hemorrhage showed a significantly lower mortality in patients randomized to simvastatin.

Therefore, although the evidence is not yet sufficient to recommend the widespread use of statins in patients with CLD/cirrhosis, providers should not avoid using statins in patients with CLD/cirrhosis who otherwise need them. In fact, they should actively look for indications that would justify their use.

Guadalupe Garcia-Tsao, MD, is professor of medicine at Yale University, chief of digestive diseases at the VA-CT Healthcare System, and director of the clinical core of the Yale Liver Center, New Haven, Conn. She had no conflicts of interest.


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

For patients with compensated cirrhosis, statin therapy was associated with about a 46% decrease in the risk of hepatic decompensation and mortality and with a 27% drop in the risk of portal hypertension and variceal bleeding, according to moderate-quality evidence from a systematic review and meta-analysis of 13 studies.

Low-quality data also suggested that statins might help protect against the progression of noncirrhotic chronic liver disease, said Rebecca G. Kim of the University of California at San Diego and her associates. “Large, pragmatic randomized controlled trials in patients with compensated cirrhosis are required to confirm these observations,” they wrote in the October issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.04.039).

Prior studies have reported mixed findings on how statin therapy affects chronic liver disease. For their review, Ms. Kim and her associates searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Cochrane Database and Systematic Reviews, Scopus, Web of Science, and PubMed for randomized controlled trials or cohort studies published through March 25, 2017. They identified 10 cohort studies and three randomized controlled trials of adults with fibrosis without cirrhosis, compensated cirrhosis, or decompensated cirrhosis that evaluated statin exposure and reported associations between exposure and outcomes related to cirrhosis. They excluded case-control studies, cross-sectional studies, and studies that focused only on the relationship between statin use and the risk of hepatocellular carcinoma.

The resulting data set included 121,058 patients with chronic liver diseases, of whom 85% had chronic hepatitis C virus infection. A total of 46% of patients were exposed to statins, which appeared to reduce their risk of hepatic decompensation, variceal bleeding, and mortality. Among 87 such patients in five studies, statin use was associated with a 46% decrease in the risk of hepatic decompensation and death, with risk ratios of 0.54 (95% confidence intervals, 0.46-0.62 and 0.47-0.61, respectively). Statin use also was associated with a 27% lower risk of variceal bleeding or progression of portal hypertension, based on an analysis of 110 events in 236 patients from three trials (RR, 0.73; 95% CI, 0.59-0.91). Finally, statin use also was associated with a 58% lower risk of fibrosis progression or cirrhosis in patients with noncirrhotic chronic liver disease, but the 95% CIs for the risk estimate did not reach statistical significance (0.16-1.11).

Source: American Gastroenterological Association

Most studies lacked data on dose and duration of statin exposure, the researchers said. However, four cohort studies reported dose-dependent effects that were most pronounced after more than a year of treatment. “Similarly, several different types of statins were studied, and observed effects were assumed to be class-specific effects,” the reviewers wrote. “However, it is possible that lipophilic and lipophobic statins may have differential efficacy in decreasing fibrosis progression.”

Together, these findings support prior studies suggesting that statin therapy is safe and can potentially reduce the risk of hepatocellular carcinoma in this patient population, they concluded. Statins “may potentially improve patient-relevant outcomes in patients with chronic liver diseases and improve survival without significant additional costs.”

The reviewers acknowledged the American Gastroenterological Association Foundation, a T. Franklin Williams Scholarship Award, the National Institutes of Health, and the National Library of Medicine. They reported having no relevant conflicts of interest.

This story was updated on 9/13/2017.