Ursodeoxycholic acid for cystic fibrosis-related liver disease

Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. This is an update of a previous review.

To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis.

We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies and searched online trial registries.Date of the most recent search of the Group's trials register: 09 April 2017.

Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis.

Two authors independently assessed trial eligibility and quality. The authors used GRADE to assess the quality of the evidence.

Twelve trials have been identified, of which four trials involving 137 participants were included; data were only available from three of the trials (118 participants) since one cross-over trial did not report appropriate data. The dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30 participants from two trials. Improvement in biliary excretion was reported in only one trial and no significant change after treatment was shown. There were no data available for analysis for long-term outcomes such as death or need for liver transplantation.

There are few trials assessing the effectiveness of ursodeoxycholic acid. The quality of the evidence identified ranged from low to very low. There is currently insufficient evidence to justify its routine use in cystic fibrosis.