Difficult-to-Treat Sclerosing Cholangitis Eased With Statins

Neil Osterweil

April 13, 2018

PARIS — Statins can significantly reduce the risk for complications and death from primary sclerosing cholangitis, results from a Swedish registry study show.

Primary sclerosing cholangitis is progressive, with no known therapy to prevent cirrhosis, liver transplant, or progression to cholangiocarcinoma, said Annika Bergquist, MD, PhD, from the Karolinska Institute in Stockholm.

However, recent evidence suggests that statins can be beneficial for patients with chronic and cholestatic liver disease, and might play a protective role in primary sclerosing cholangitis, she explained here at the International Liver Congress 2018.

Bergquist and her colleagues drew on comprehensive birth-to-death Swedish registry data to explore the effects of different drugs, including statins, on the risk for death, liver transplantation, liver cancer, and variceal bleeding in patients with primary sclerosing cholangitis.

The team identified 2914 primary sclerosing cholangitis patients with data available on drug prescriptions, cancer status, general health, and death.

Drug exposure from the time of first prescription fulfillment was assessed on multivariate Cox regression analysis, with adjustments for age at diagnosis of primary sclerosing cholangitis, date of diagnosis, date of diagnosis of inflammatory bowel disease, and sex.

The association with inflammatory bowel disease is strong. In Sweden, approximately 80% of primary sclerosing cholangitis patients have inflammatory bowel disease, Bergquist reported.

In the study cohort, 58.3% of the patients also had a diagnosis of ulcerative colitis, 12.4% had a diagnosis of Crohn's disease, and 29.2% had mixed presentation of the two conditions.

Statins were associated with a 32% reduction in all-cause mortality, a 50% decrease in the combined end point of death and liver transplantation, and a 47% reduction in adverse liver events.

Table. Hazard Ratios for Events Related to Primary Sclerosing Cholangitis

Drug or Class All-Cause Mortality Mortality and Liver Transplantation Adverse Liver Events
Antibiotic 1.70 2.27 3.03
Antimycotic 2.78 3.13 1.74
Aspirin 0.99 2.16 3.35
Azathioprine 0.66 0.65 0.80
Metronidazole 1.27 1.20 1.58
NSAID 0.86 0.82 0.87
Statin 0.68 0.50 0.53
Steroid 1.94 2.14 1.28
Ursodeoxycholic acid 1.04 1.34 3.10

 

The Swedish registry data were very high quality. Follow-up was nearly complete and the team was able to eliminate all patients with sclerosing cholangitis secondary to other conditions. However, they were unable to capture drug indications or the clinical status of patients, and information was lacking on potential confounding factors, such as alcohol use and smoking, and on compliance, Bergquist acknowledged.

After the briefing during which Bergquist presented the findings, Medscape Medical News asked whether these data suggest that azathioprine also has a protective effect.

"Azathioprine is used very much in inflammatory bowel disease and, therefore, it is difficult to say whether this has an impact on the primary sclerosing cholangitis itself," she explained.

Specific Statins

The specific statins used might have had an influence on outcomes, said briefing moderator Annalisa Berzigotti, MD, PhD, from the University of Bern in Switzerland.

"Simvastatin, in studies that have been done on cirrhosis, which are quite extensive, and also in vitro, has a particular pharmacokinetic and pharmacodynamic effect, and it is able to penetrate better into cells," she told Medscape Medical News.

Bergquist said she agrees, noting that simvastatin has antifibrotic, antiangiogenic, and antivasoconstrictive effects, which help to improve portal hypertension.

This early work is "not the basis for treating everyone with statins," Bergquist emphasized. But "it is a class effect — what we observe with statins in liver disease — and it is possible that simvastatin is slightly superior."

This study was supported by the Karolinska Institute. Bergquist and Berzigotti reported no relevant conflicts of interest,

International Liver Congress (ILC) 2018. Abstract PS-128. Presented April 12, 2018.

Follow Medscape Gastro on Twitter @MedscapeGastro and Neil Osterweil @NeilOsterweil

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