Statin Use Is Associated With Improved Outcomes of Patients With Primary Sclerosing Cholangitis

Abstract

BACKGROUND & AIMS: There is increasing evidence that statins can benefit patients with chronic liver diseases, but their effects have not been studied in patients with primary sclerosing cholangitis (PSC). We performed a nationwide study in Sweden to determine the effects of exposure to drugs, including statins, in patients with PSC. METHODS: We studied a population-based cohort of patients in Sweden with PSC and concomitant ulcerative colitis or Crohn's disease from 2005 through 2014 (n [ 2914), followed through 2016. We collected analyzed data from the patient register, the prescribed drug register, the death certificate register and the cancer register. We calculated risk or death, liver transplantation, bleeding of esophageal varices, and cancer in relation to drug exposure. RESULTS: The mean age of patients at the time of diagnosis with PSC was 41.4 years (inter-quartile range [IQR], 25.6-56.1 years). The total follow-up time was 11769 person-years, during which 3.4% of patients received liver transplants and 19.9% died. Proportions of patients exposed to drugs were: ursodeoxycholic acid, 60.2%; 5-aminosalicylic acid, 74.4%; azathioprine or mercaptopurins, 33.7%; and statins, 13.9%. Statin use was associated with a reduced risk of all-cause mortality (hazard ratio [HR], 0.68; 95% CI, 0.54-0.88) and death or liver transplantation (HR, 0.50; 95% CI, 0.28-0.66). Use of azathioprine was also associated with reduced mortality (HR, 0.66; 95% CI, 0.52-0.84) and risk of death or liver transplantation (HR, 0.65; 95% CI, 0.50-0.83). Exposure to ursodeoxycholic acid did not affect mortality (HR, 1.04; 95% CI, 0.87-1.25). CONCLUSION: In a population-based cohort of patients in Sweden with PSC, we associated use of statins and azathioprine with decreased risks of death and death or liver transplantation. Exposure to ursodeoxycholic acid was not associated with reduced mortality.

Cirrhosis as new indication for statins

“…Recently, the effect of statins on PSC was evaluated in a nationwide observational study in Sweden 1 13. The study included all patients diagnosed in Sweden with PSC and concomitant UC or Crohn’s disease from 2005 through 2014.…”

“…These include reduction in portal pressure, improved liver sinusoidal endothelial and hepatic microvascular dysfunction, decreased fibrogenesis, protection against ischaemia/reperfusion injury, safe prolongation of ex vivo liver graft preservation, reduced sensitivity to endotoxin-mediated liver damage, protection from acute-on-chronic liver failure (ACLF), prevention of liver injury following hypovolaemic shock and preventing/delaying progression of cirrhosis of any aetiology 7–12. Moreover, statins have been shown to have potential beneficial effects in the progression of other liver diseases, such as chronic sclerosing cholangitis and in preventing hepatocellular carcinoma (HCC) 13–15. Because of these many theoretically favourable effects, statins have evolved from being considered a risk to kind of wonder drugs for patients with chronic liver disease (CLD) 2.…”

Confounding and bias in observational studies in inflammatory bowel disease: a meta‐epidemiological study

“…Example for ‘yes’: ‘Additional limitations caused by the lack of clinical data are residual confounding from for example alcohol abuse, smoking, diabetes or obesity’ 20 …”

Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities

“…Existing data are limited to case reports and a prospective case series (n = 15, median 41 months of treatment) [158], and although improvement in ALP (mean DALP -557 [-55.8%]; ALP normalized in 5/15 patients) and histology (6/10, 2/10 and 2/10 showed improved, stable or worsened histology, respectively) was reported in this series, there were no convincing data of effect on clinical outcomes. Of note, a Swedish population based registry study have suggested an impact from azathioprine (and statins) on clinical outcomes in PSC [159], so further and more targeted assessments to this end may still be considered.…”