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Review
. 2017 Sep 11;9(9):CD000222.
doi: 10.1002/14651858.CD000222.pub4.

Ursodeoxycholic acid for cystic fibrosis-related liver disease

Katharine Cheng  1 , Deborah Ashby, Rosalind L Smyth
Affiliations
Review

Ursodeoxycholic acid for cystic fibrosis-related liver disease

Katharine Cheng et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

Objectives: 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 methods: 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.

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.

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Conflict of interest statement

The lead author of this review, Katharine Cheng, has been employed by GlaxoSmithKline Research and Development Ltd since late 2004. GlaxoSmithKline does not produce or market any drugs that may fall into the scope of this review.

Deborah Ashby and Rosalind Smyth declare no potential conflicts of interest.

Figures

1.1
1.1. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 1: Lack of normalisation of any liver enzyme reported in the trial
1.2
1.2. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 2: Lack of normalisation of all liver enzymes reported in the trial
1.3
1.3. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 3: Lack of normalisation of 5' nucleotidase
1.4
1.4. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 4: Lack of normalisation of aspartate transaminase
1.5
1.5. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 5: Lack of normalisation of alanine transferase
1.6
1.6. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 6: Lack of normalisation of gammaglutamate transferase
1.7
1.7. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 7: Need for liver transplantation
1.8
1.8. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 8: Death related to liver disease
1.9
1.9. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 9: Death due to all causes
1.10
1.10. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 10: Change in weight (kg)
1.11
1.11. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 11: Development of portal hypertension
1.12
1.12. Analysis
Comparison 1: UDCA versus placebo/no additional treatment (all groups given 'conventional care'), Outcome 12: Development of complications of portal hypertension
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References

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