Background: Primary sclerosing cholangitis is a chronic cholestatic disease of intrahepatic and extrahepatic biliary ducts, characterised by chronic periductal inflammation and sclerosis of the ducts, which results in segmental stenoses of bile ducts, cholestasis, fibrosis, and ultimately, liver cirrhosis. Patients with primary sclerosing cholangitis are at higher risk of cholangiocarcinoma as well as of colonic neoplasia, since primary sclerosing cholangitis is associated with inflammatory bowel disease in more than 80% of the patients. Several therapeutic modalities have been proposed for primary sclerosing cholangitis, like ursodeoxycholic acid, glucocorticosteroids, and immunomodulatory agents, but none has been successful in reversing the process of the disease. To date, liver transplantation is the only definite therapeutic solution for patients with advanced primary sclerosing cholangitis with liver cirrhosis.
Objectives: To assess the beneficial and harmful effects of glucocorticosteroids for patients with primary sclerosing cholangitis.
Search strategy: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, and LILACS from their inception until September 2009, as well as reference lists.
Selection criteria: Randomised clinical trials comparing any dose or duration of glucocorticosteroids versus placebo, no intervention, or other immunosuppressive agents. We included trials irrespective of language, blinding, or publication status.
Data collection and analysis: Authors extracted data independently and assessed the methodological quality by the generation of the allocation sequence, allocation concealment, double blinding, follow-up, incomplete outcome data reporting, selective reporting, baseline imbalance, and early stopping. The results of the meta-analyses were presented as relative risks (RR) or mean difference (MD), both with 95% confidence intervals (CI). The primary outcome measures were mortality and liver-related morbidity.
Main results: Two randomised clinical trials were eligible for inclusion. One trial compared biliary lavage with hydrocortisone versus saline in 17 patients. Hydrocortisone tended to increase adverse events (pancreatitis, cholangitis with septicaemia, paranoid ideas, fluid retention) (RR 3.43, 95% CI 0.51 to 22.9) and had no cholangiographic improvement, which led to termination of the trial. The other trial compared budesonide versus prednisone in 18 patients. Patients had statistically significant higher serum bilirubin concentration after treatment with prednisone compared with budesonide (MD 10.4 micromol/litre, 95% CI 1.16 to 19.64 micromol/litre). No other statistically significant effects on clinical or biochemical outcomes were reported on any of the evaluated interventions.
Authors' conclusions: There is no evidence to support or refute peroral glucocorticosteroids for patients with primary sclerosing cholangitis. The intrabiliary application of corticosteroids via nasobiliary tube seems to induce severe adverse effects.