New research shows that statins have the potential to modify the disease in people with non-cirrhotic chronic liver disease (CKD), reducing the risk of progression to severe liver disease.
A Swedish population-based study showed that adults with non-cirrhotic CLD treated with statins had a statistically significant 40% lower risk of developing severe liver disease compared to comparable patients not treated with statin therapy.
Statin users were also less likely to progress cirrhosis of the liver or hepatocellular carcinoma (HCC) and die from liver disease, reports Rajani Sharma, MD, MS, Department of Digestive and Liver Diseases, Columbia University Irving Medical Center in New York, and colleagues.
Their study published online V Clinical Gastroenterology and Hepatology.
More than just lowering cholesterol
This study “continues the theme that cholesterol-lowering statins are useful for more than just lowering cholesterol levels,” said William Carey, MD, who was not involved in the study. Medscape Medical News.
The results are “very consistent with other studies that show that people with liver disease who take statins do better in many ways than those who do not take statins,” said Carey, Acting Head of Hepatology, Division of Gastroenterology, Hepatology and nutrition. , Cleveland Clinic, Ohio.
“The effects are not trivial,” Carey added. “This is a very significant benefit in terms of fibrosis progression and survival.”
Statins have been shown to inhibit inflammatory pathways, stimulate endothelial cell function, and reduce hepatic stellate cell activity, suggesting that statins may reduce the progression of liver fibrosis, write Sharma et al.
Several previous studies have examined the effects of statins on non-cirrhotic CLD, but most have only included patients with viral hepatitisand the identification of precirrhotic liver disease was largely based on fibrosis scores or International Classification of Diseases (ICD) coding, leading to the risk of misclassification and heterogeneity of results, they write.
Using histopathology data from a nationwide Swedish cohort, Sharma and colleagues identified 3862 adults with CLD without cirrhosis who were taking statins and a similar number of CLD patients without cirrhosis who were not taking statins with an appropriate propensity score. Adults with CLD included in the study must have had a liver biopsy showing fibrosis or inflammation between 1969 and 2017 and at least one ICD code for CLD.
In both groups, 45% of patients had non-alcoholic fatty liver liver disease (NAFLD), 22% had alcoholic liver disease (ALD), 18% had viral hepatitis, and 15% had autoimmune hepatitis (AIH).
The analysis showed that 234 (6.1%) statin users developed severe liver disease compared to 276 (7.1%) non-statin users, with incidence rates of 10.5 versus 18.1 per 1,000 person-years, respectively .
Statin use was associated with a statistically significant 40% reduction in severe liver disease (hazard ratio [HR]0.60; 95% CI, 0.48–0.74).
This was the case for 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).
The researchers report that statin use had a protective association both at pre-fibrosis and at diagnosis stages of fibrosis.
Statin use was also associated with lower rates of progression to cirrhosis (RR, 0.62; 95% CI, 0.49–0.78), HCC (RR, 0.44; 95% CI, 0.27–0.71) and liver-related death or liver transplant (RR, 0.55; 95% CI, 0.36–0.82).
The authors note that their “study provides the most reliable estimates currently available.” However, they caution that “prospective randomized controlled trials are needed to recommend the use of statins in clinical practice.”
“Reassuring and pleasantly surprising”
The study is “very interesting, encouraging, and pleasantly surprising,” said Scott L. Friedman, MD, chief of liver disease and dean of therapeutic discovery at the Icahn School of Medicine at Mount Sinai in New York. Medscape Medical News.
“Statins have been around for a long time and used to be feared because they can cause liver damage. But numerous and consistent data rule out the possibility that they are more toxic in patients with liver disease,” Friedman said. , which was not associated with this study.
“What is interesting and new about this article is that those studies that have looked at the effects of statins on liver disease have mostly focused on patients with cirrhosis because there is some scientific evidence. [that] statins can lead to vasodilation and reduce the increased blood flow to the liver that occurs with cirrhosis,” he explained.
“Instead, this rather large study included patients who did not have evidence of liver cirrhosis on biopsy. The results show that statins have a significant protective effect in these patients,” Friedman said.
The study was supported by the Karolinska Institute in Sweden, Columbia University Irving Medical Center, Swedish Research Council, Swedish Cancer Society and US National Institutes of Health. Sharma is a consultant for Takeda and Volv. Other contributors report current or past relationships with BMS, Gilead, Salix, and GlaxoSmithKline. Carey and Friedman do not report a related financial relationship.
Clin Gastroenterol Hepatol. Published online April 28, 2023 Abstracts
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