WASHINGTON — , according to a study presented at Digestive Disease Week® (DDW) 2024.
Statin use was associated with an 86% risk reduction, and only .09% of IBD patients who took statins developed PSC.
“We all take care of patients with liver disease, and we know what a significant burden PSC is. These patients have a significantly elevated risk of enhanced fibrosis and cirrhosis, multiple cancers, and cholangitis and sepsis,” said lead author Chiraag Kulkarni, MD, a gastroenterology fellow at Stanford (California) University Medical School.
“Despite this, we have to date no proven effective medical care for PSC,” he said. “However, over the last decade, there is growing evidence that statins may be beneficial in liver disease, and we see this evidence base stretching from basic science to clinical data.”
Dr. Kulkarni pointed to numerous studies that indicate statins may slow disease progression in steatotic liver disease, viral hepatitis, and cirrhosis. But could statins prevent the onset of PSC?
Because PSC incidence is low, Dr. Kulkarni and colleagues focused on a patient population with higher prevalence — those with IBD, who have an overall lifetime risk of 2% to 7%. The research team followed patients from the date of IBD diagnosis.
Among 33,813 patients with IBD in a national dataset from 2018 onward, 8813 used statins. Statin users tended to be older than non–statin users.
Overall, 181 patients developed new onset PSC during a median follow-up of about 45 months after initial IBD diagnosis. Only eight statin users (.09%) developed PSC, compared with 173 patients (.69%) in the control group.
In a propensity score-matched analysis, statin therapy was associated with a significantly lower risk of developing PSC (HR .14, P < .001). The associated E-value was 5.5, which suggested a robust finding and unlikely to be due to non-visible confounding.
The findings were consistent across secondary and sensitivity analyses, including by age, duration of statin use, and type of statin. For instance, for patients under age 50 where PSC is more likely to occur, statins were associated with a 90% reduction in PSC risk.
“We take away two things from this. First, it’s suggested that a protective effect occurs at ages where PSC is most likely to occur,” Dr. Kulkarni said. “Second, in combination with our propensity score-matched analysis, the results we are observing are not due to a survival bias, where the patients who survive to an age where statins are prescribed simply have a biologically different predilection for developing PSC.”
Statins also protected against PSC in both ulcerative colitis (HR .21) and Crohn’s disease (HR .15), as well as both women (HR .16) and men (HR .22).
Given the uncertainty about the optimal duration of statin therapy for a protective effect, Dr. Kulkarni and colleagues looked at a lag time of 12 months. They found statins were associated with an 84% risk reduction (HR .16), which was similar to the primary analysis.
The study was limited by the inability to capture dosage data or medication adherence. The findings raised several questions, Dr. Kulkarni said, such as the underlying mechanisms and clinical implications. For instance, the underlying mechanisms appear to be related to the pleiotropic effect of statins, modulation of gut inflammation, and alterations in bile acid profiles.
“This is really fascinating and interesting. I wonder about this as a primary prevention strategy in those who have normal cholesterol. Could this work or not?” said Gyongyi Szabo, MD, AGAF, chief academic officer at Beth Israel Deaconess Medical Center, Boston, who was a moderator for the Liver & Biliary Section Distinguished Abstract Plenary Session.
Beth Israel Deaconess Medical Center
Dr. Gyongyi Szabo
Dr. Kulkarni noted that these findings wouldn’t change clinical practice alone, but based on existing literature around statin hesitancy among patients with cardiovascular disease, the risk reduction for PSC could provide another reason to encourage patients to take them.
“To move this to a place where you can actually think about primary prevention, I think the biological mechanisms need to be teased out a little bit more,” Dr. Kulkarni said. “Then I think you probably still need to identify a higher-risk group than IBD alone.”
Dr. Kulkarni declared no disclosures.