Ursodeoxycholic acid for liver disease related to cystic fibrosis

Review question

Does ursodeoxycholic acid improve measures of liver function, reduce the risk of developing chronic liver disease and improve outcomes in general in people with cystic fibrosis?


Problems with the consistency of bile (thickened) and how it flows cause liver disease in up to 20% of young people with cystic fibrosis. Bile ducts can become blocked and cause cirrhosis in one or more parts of the liver. Ursodeoxycholic acid is a naturally occurring bile acid which is taken as either a tablet or liquid to try and prevent liver disease in people with cystic fibrosis. The best response seems to be from a total dose of 20 mg/kg/day in two to three separate doses and given initially for several months but possibly indefinitely. Originally it was used to treat gallstones, but over the last few years it has been used to treat and prevent the progression of cystic fibrosis-related liver disease. This is an updated version of the review.

Search date

We last searched for evidence on 09 April 2017.

Study characteristics

We searched for trials of ursodeoxycholic acid lasting for at least three months and were able to include four trials, but data for analysis were only available from three of these. There are data from 118 participants aged between four and 32 years in this review. The dose of the drug given in the three trials with data ranged from 10 to 20 mg/kg/day. Two of these trials compared ursodeoxycholic acid to tablets with no medicine in them (placebo) and the third trial compared ursodeoxycholic acid to 'usual' treatment. The complex design of two trials meant data could not be analysed for all the participants. The trials lasted for up to 12 months, but no longer; however, one trial did report some follow-up data after nine years.

Key results

Not many of the outcomes we listed in our review were assessed; only weight gain, skinfold thickness and biliary excretion. There were no real differences between treatments for any of these outcomes. Long-term outcomes that we think are important, such as death or the need for liver transplant, were only reported in the follow-up of one trial and the information did not tell us if the people who died or needed a liver transplant had received ursodeoxycholic acid or placebo.

Current research shows that side effects of this treatment are rare, but there is not enough information about using it in the long-term to justify routinely giving it to people with cystic fibrosis. As there is no other treatment to prevent liver disease, more research on ursodeoxycholic acid is needed.

Quality of the evidence

The trials seemed to be well organised and well run, but there was not always enough information to judge them properly. While, on the whole, we do not think that any factors linked to how the trials were run would influence the results greatly, we did have some concerns that in one trial the group taking ursodeoxycholic acid were generally not as healthy at the start of the trial as the group taking placebo. Also, in another trial there were some people who withdrew and were not included in the final analysis, but no reasons for this were given. Overall, we judged the quality of the evidence we found to be low or very low.

Authors' conclusions: 

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.

Read the full abstract...

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.

Search strategy: 

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.

Selection criteria: 

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.

Data collection and analysis: 

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

Main results: 

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.