Bile acids for primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterised by progressive inflammation and scarring of liver bile ducts. Destruction of bile ducts leads to incidence of bile flow to the gut, resulting in the development of biliary cirrhosis and end-stage liver disease. PSC is most common in young males and its aetiology is still not fully understood. The disease is usually classified as an autoimmune disorder, but other aetiological factors cannot be excluded. There is a strong association of PSC with inflammatory bowel diseases, particularly ulcerative colitis, which coexists in approximately 70% of patients. Besides its progressive and irreversible nature, PSC is also associated with an increased risk for cholangiocarcinoma, which contributes to an even higher morbidity and mortality of this disease.

The diagnosis of primary sclerosing cholangitis is based on a combined approach that includes clinical, laboratory, and imaging findings. Since the disease is usually asymptomatic in its initial stage, early recognition and diagnosis is actually rather rare. Because of poor understanding of aetiology and pathogenesis, treatment of PSC is still not satisfactory. Numerous medications have been evaluated for therapy of PSC, but most of them showed none or minimal effect, and certain drugs were associated with serious adverse events. Bile acids have also been considered for the treatment of PSC demonstrating a possible beneficial effect. However, further investigation of their role in PSC therapy is needed. Therefore, the treatment of choice for patients with end-stage liver disease due to PSC remains liver transplantation. Despite the relatively low incidence of PSC in the general population, PSC remains among the most common indications for liver transplantation in Europe and the United States.

Based on eight randomised clinical trials of high risk of bias, the administration of ursodeoxycholic acid to patients with primary sclerosing cholangitis did not significantly reduce mortality, hepatic decompensation, need for liver transplantation, liver histological deterioration, or radiological deterioration compared with placebo or no intervention. The use of ursodeoxycholic acid showed a statistically significant improvement of liver biochemistry. However, evidence of these beneficial effects is weak as it is produced from trials with high risk of bias and a rather small number of patients. Furthermore, these observations are at risk of outcome measure reporting bias as half or less than half of the trials reported on these outcomes. One trial assessed the self-estimated quality of life of patients with primary sclerosing cholangitis treated with ursodeoxycholic acid. No significant difference was found in any of the studied components, physical as well as mental. Based on an analysis of six of the eight included trials, the use of ursodeoxycholic acid seemed safe and well tolerated, without reports of serious adverse events. We were unable to identify trials evaluating other bile acids for patients with primary sclerosing cholangitis. Accordingly, the evidence does neither support nor refute bile acids for primary sclerosing cholangitis.

Authors' conclusions: 

We did not find enough evidence to support or refute the use of bile acids in the treatment of primary sclerosing cholangitis. However, bile acids seem to lead to a significant improvement in liver biochemistry. Therefore, more randomised trials are needed before any of the bile acids can be recommended for this indication.

Read the full abstract...

Primary sclerosing cholangitis is a progressive chronic cholestatic liver disease that usually leads to the development of cirrhosis. Studies evaluating bile acids in the treatment of primary sclerosing cholangitis have shown a potential benefit of their use. However, no influence on patients survival and disease outcome has yet been proven.


To assess the beneficial and harmful effects of bile acids for patients with primary sclerosing cholangitis.

Search strategy: 

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded generally from inception through to October 2010.

Selection criteria: 

Randomised clinical trials comparing any dose of bile acids or duration of treatment versus placebo, no intervention, or another intervention were included irrespective of blinding, language, or publication status.

Data collection and analysis: 

Two authors extracted data independently. We evaluated the risk of bias of the trials using prespecified domains. We performed the meta-analysis according to the intention-to-treat principle. We presented outcomes as relative risks (RR) or mean differences (MD), both with 95% confidence intervals (CI).

Main results: 

Eight trials evaluated ursodeoxycholic acid versus placebo or no intervention (592 patients). The eight randomised clinical trials have a high risk of bias. Patients were treated for three months to six years (median three years). The dosage of ursodeoxycholic acid used in the trials ranged from low (10 mg/kg body weight/day) to high (28 to 30 mg/kg body weight/day). Ursodeoxycholic acid did not significantly reduce the risk of death (RR 1.00; 95% CI 0.46 to 2.20); treatment failure including liver transplantation, varices, ascites, and encephalopathy (RR 1.22; 95% CI 0.91 to 1.64); liver histological deterioration (RR 0.89; 95% CI 0.45 to 1.74); or liver cholangiographic deterioration (RR 0.60; 95% CI 0.23 to 1.57). Ursodeoxycholic acid significantly improved serum bilirubin (MD -14.6 µmol/litre; 95% CI -18.7 to -10.6), alkaline phosphatases (MD -506 IU/litre; 95% CI -583 to -430), aspartate aminotransferase (MD -46 IU/litre; 95% CI -77 to -16), and gamma-glutamyltranspeptidase (MD -260 IU/litre; 95% CI -315 to -205), but not albumin (MD -0.20 g/litre; 95% CI -1.91 to 1.50). Ursodeoxycholic acid was safe and well tolerated by patients with primary sclerosing cholangitis.