Background: Primary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease without medical cure, that confers a significantly elevated risk of malignancy, acute cholangitis and cirrhosis. Approximately 2-7% of patients with inflammatory bowel disease (IBD) will develop PSC. There are no approved chemoprophylactic agents available to prevent onset of de novo PSC in IBD. In PSC, the use of statin has been associated with reduced episodes of acute cholangitis and increased transplant-free survival. However, the impact of statins on the development of de novo PSC is unknown.

Methods: We conducted a retrospective cohort study of patients with existing IBD using a large representative national database with and without statin exposure. Patients were followed from the date of diagnosis of IBD. Patient demographics, co-morbidities, medications, PSC disease severity, and IBD disease status were extracted. Unmatched, basic matched, and propensity score-matched Cox regression was performed. E-values were calculated.

Results: Our analysis included 33,813 patients with IBD of whom 8,813 were exposed to statins. 181 patients developed new onset PSC over a median follow-up of approximately 44.5 months after the index diagnosis of IBD. Only eight patients (0.09%) in the statin arm developed PSC, while 173 (0.69%) in the control arm did. In propensity score-matched analysis, statin therapy was associated with a significantly lower risk of developing PSC (HR 0.14; 95% CI 0.06-0.33, p<0.001). The associated E-value was 5.5 suggesting this finding is robust and unlikely to be due to non-visible confounding. The findings were consistent across multiple secondary and sensitivity analyses, including stratification by age group, duration of statin use and type of statin.

Conclusions: In a propensity score-matched analysis of a large, nationally representative dataset, statin use was associated with an 86% reduction in the risk of new PSC diagnosis among patients with known IBD suggesting a possible benefit as a chemoprophylactic agent. These findings warrant prospective validation and provide a strong rationale for further investigation, which may develop novel mechanistic and therapeutic insights into PSC.

Figure 1. Time to onset of PSC with statin therapy

Chiraag Kulkarni

Stanford University

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