Primary sclerosing cholangitis - Emerging treatments

Statins

A large population-based cohort study in Sweden suggests that statins may decrease all-cause mortality (hazard ratio [HR] 0.68, 95% CI 0.54 to 0.88), and death or liver transplantation (HR 0.50, 95% CI 0.28 to 0.66), in patients with primary sclerosing cholangitis.[86] The results may be helpful in informing future treatment pathways.

Azathioprine

A large population-based cohort study in Sweden suggests that the use of azathioprine is associated with reduced mortality (HR 0.66, 95% CI 0.52 to 0.84), and risk of death or liver transplantation (HR 0.65, 95% CI 0.50 to 0.83), in patients with primary sclerosing cholangitis.[86] Azathioprine is not recommended for the treatment of PSC, but the results may be helpful in informing future treatment pathways.[34]

Vancomycin

Case reports, pilot studies, and small randomized controlled trials suggest that oral vancomycin may have a role in the management of PSC.[2][3][87][88][89][90] At present, however, there is insufficient evidence to recommend vancomycin or any antibiotic in the absence of recurrent bacterial cholangitis.[2][3]

Fecal microbiota transplant

The results of one open-label pilot study of 10 patients with primary sclerosing cholangitis and concurrent inflammatory bowel disease (9 with ulcerative colitis, and 1 with Crohn disease) suggest that fecal microbiota transplant (FMT) may be of some benefit.[91] Three patients experienced a ≥50% decrease in alkaline phosphatase (ALP) levels. Bacterial diversity in the gut increased in all patients post-FMT, as early as week 1, and abundance of engrafter operational taxonomic units in patients post-FMT correlated with decreased ALP levels (P=0.02).

Obeticholic acid

A randomized, placebo controlled phase 2 trial showed that obeticholic acid, a farnesoid X receptor agonist reduced serum ALP levels in patients with PSC.[92] However, data that show a decrease in mortality or risk of liver transplantation are lacking.

Norursodeoxycholic acid

Norursodeoxycholic acid, a homologue of ursodiol (ursodeoxycholic acid), decreases ALP levels in a dose-dependent fashion in patients with PSC, but there has been no evidence of a reduction in mortality or risk of liver transplantation.[93]

Bezafibrate

Bezafibrate, a peroxisome proliferator-activated receptor agonist, has been found to be effective in alleviating itch in patients with PSC in the FITCH (fibrates for cholestasis-associated itch) trial.[94] Short-term treatment with bezafibrate has not shown any major adverse effects.[94] Bezafibrate is recommended by the European Association for the Study of the Liver (EASL) for the treatment of moderate to severe pruritus in patients with PSC.[2] However, it is not approved in the US.