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.[85] 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.[85] 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 randomised controlled trials suggest that oral vancomycin may have a role in the management of PSC.[2][3][86][87][88][89] At present, however, there is insufficient evidence to recommend vancomycin or any antibiotic in the absence of recurrent bacterial cholangitis.[2][3]

Faecal 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's disease) suggest that faecal microbiota transplant (FMT) may be of some benefit.[90] 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 randomised, placebo controlled phase 2 trial showed that obeticholic acid, a farnesoid X receptor agonist reduced serum ALP levels in patients with PSC.[91] However, data that show a decrease in mortality or risk of liver transplantation are lacking.

Norursodeoxycholic acid

Norursodeoxycholic acid, a homologue of 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.[92]

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.[93] Short-term treatment with bezafibrate has not shown any major adverse effects.[93] 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.