Statins Appear to Guard Against Liver Disease Progression

Statins have disease-modifying potential in people with non-cirrhotic chronic liver disease (CLD) by reducing the risk for progression to severe liver disease, new research shows.

The Swedish population-based study found that adults with non-cirrhotic CLD who were on statin therapy had a statistically significant 40% lower risk of developing severe liver disease compared with matched patients who were not on statin therapy.

The statin users were also less apt to progress to cirrhosis or hepatocellular carcinoma (HCC) and to die of liver disease, report Rajani Sharma, MD, MSc, Division of Digestive and Liver Diseases, Columbia University Irving Medical Center in New York City, and colleagues.

Their study is published online in Clinical Gastroenterology and Hepatology.

More Than Just Cholesterol-Lowering

This study "continues the theme that cholesterol-lowering statins are good for a lot more things than just lowering cholesterol," William Carey, MD, who wasn’t involved with the study, told Medscape Medical News.

The results are "very consistent with other trials that show that people with liver disease on statins do better in many respects than those who are not on statins," said Carey, acting head of the hepatology section, department of gastroenterology, hepatology, and nutrition, Cleveland Clinic, Ohio.

"The effects are not trivial," Carey added. "It's a very significant advantage in terms of fibrosis progression and survival."

Statins have been shown to inhibit inflammatory pathways, promote endothelial cell function, and reduce hepatic stellate cell activity, suggesting that statins could lessen the progression of liver fibrosis, Sharma and co-authors write.

A few prior studies have looked at the effects of statins in non-cirrhotic CLD specifically, but most only included patients with viral hepatitis, and the identification of pre-cirrhotic liver disease was largely based on fibrosis scores or International Classification of Disease (ICD) coding, leading to a risk for misclassification and heterogeneity in results, they write.

Using histopathology data in a nationwide Swedish cohort, Sharma and colleagues identified 3862 adults with non-cirrhotic CLD who were statin users and a like number of propensity score–matched non-statin users with non-cirrhotic CLD. The adults with CLD included in the study were required to have a liver biopsy showing fibrosis or inflammation between the years 1969 and 2017 and at least one ICD code for CLD.

In both groups, 45% of patients had nonalcoholic fatty liver disease (NAFLD), 22% had alcohol-related liver disease (ALD), 18% had viral hepatitis, and 15% had autoimmune hepatitis (AIH).

The analysis found 234 (6.1%) statin users developed severe liver disease vs 276 (7.1%) non-users, with incidence rates of 10.5 vs 18.1 per 1000 person-years, respectively.

Statin use was associated with a statistically significant 40% lower rate of severe liver disease (hazard ratio [HR], 0.60; 95% CI, 0.48 - 0.74).

This was the case in ALD (HR, 0.30; 95% CI, 0.19 - 0.49) and NAFLD (HR, 0.68; 95% CI 0.45 - 1.00), but the results were not statistically significant for individuals with viral hepatitis (HR, 0.76; 95% CI, 0.51 - 1.14) or AIH (HR, 0.88; 0.48 - 1.58).

Statin use had a protective association in both pre-fibrosis and fibrosis stages at diagnosis, the researchers report.

Statin use was also associated with lower rates of progression to cirrhosis (HR, 0.62; 95% CI, 0.49 - 0.78), HCC (HR, 0.44; 95% CI, 0.27 - 0.71), and liver-related death or liver transplant (HR, 0.55; 95% CI, 0.36 - 0.82).

The authors note that their "study provides the most robust estimates available thus far." However, they caution that "prospective randomized controlled trials are necessary in order to recommend statin use in clinical practice."

"Reassuring and Pleasantly Surprising"

The study is "very interesting, reassuring, and pleasantly surprising," Scott L. Friedman, MD, chief of the Division of Liver Diseases and dean for Therapeutic Discovery at the Icahn School of Medicine at Mount Sinai in New York, told Medscape Medical News.

"Statins have been around for a long time, and in earlier days, there was fear of using them because they might induce liver injury. But ample and consistent data exclude the possibility that they are more toxic in patients with liver disease," said Friedman, who was not associated with this research.

"What's interesting and new about this paper is that those studies that have looked at the effects of statins on liver disease have primarily focused on patients who have cirrhosis because there's some scientific evidence [that] statins can lead to vasodilation and reduce the elevated liver blood flow that occurs in cirrhosis," he explained.

"Instead, this study, which is quite sizable, includes patients who do not have evidence of cirrhosis based on biopsies. The results suggest that statins have a significant protective effect in these patients," Friedman said.

The study was supported by the Karolinska Institute in Sweden, the Columbia University Irving Medical Center, the Swedish Research Council, The Swedish Cancer Society, and the US National Institutes of Health. Sharma is a consultant for Takeda and Volv. Other co-authors report current or past relationships with BMS, Gilead, Salix, and GlaxoSmithKline. Carey and Friedman report no relevant financial relationships.

Clin Gastroenterol Hepatol. Published online April 28, 2023. Abstract

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