Ursodeoxycholic acid for cystic fibrosis-related liver disease

c/o Cochrane Cystic Fibrosis & Genetic Disorders Review Group, Institute of Child Health, University of Liverpool, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, UK, L12 2AP.
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 01/2012; 10(10):CD000222. DOI: 10.1002/14651858.CD000222.pub2
Source: PubMed

ABSTRACT Cystic fibrosis-related liver disease peaks in adolescence with up to 20% of people 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.
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.Date of the most recent search of the Group's trials register: 10 July 2012.
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.
Ten trials have been identified, of which three trials involving 118 participants were included. 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. Long-term outcomes such as death or need for liver transplantation were not reported.
There are few trials assessing the effectiveness of ursodeoxycholic acid. There is insufficient evidence to justify its routine use in cystic fibrosis.

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    • "There is evidence of improved liver biochemistry (Desmond et al., 2007) shortly after introducing UDCA and improved histological features of liver disease afterwards (Linblad et al., 1998). However, evidence of improved outcomes such as reduced need for transplantations or improved survival is lacking (Cheng et al., 2000). UCDA is widely used as it is the only available therapeutic agent and is generally well tolerated with few side effects. "
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    ABSTRACT: Evidence of chronic liver disease is found in 25% of patients with cystic fibrosis (CF) and is the cause of liver decompensation in 2-3%. Liver injury is secondary to bile duct plugging and secondary bile-acid-related toxicity; almost all cases present in the first two decades of life.The marked variation in the presence and severity of disease may be due to modifier genes. Most cases are detected on routine screening and only a small proportion present with variceal bleeding, ascites or persistent jaundice. Abnormalities of liver function tests have a low sensitivity and specificity and the presence of established cirrhosis will be diagnosed on imaging. There is some evidence that the biliary liver disease of CF responds to ursodeoxycholic acid, although the degree of benefit remains uncertain. Liver transplantation has been successfully undertaken in the presence of isolated liver decompensation with maintained pulmonary function. Specific complications of cirrhosis including variceal haemorrhage, ascites and encephalopathy are managed by standard techniques applicable to all types of cirrhosis.There is accumulating evidence that established compensated cirrhosis does not adversely affect the outcome from lung transplantation.
    Portal Hypertension - Causes and Complications, 03/2012; , ISBN: 978-953-51-0251-9
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    ABSTRACT: This article aims to review the physiopathology, diagnosis and treatment of cystic fibrosis-related dyslipidemia (CFD). Bibliographic searches of the Medline and Latin American and Caribbean Health Sciences Literature databases were made (year range, 1987-2007), and the most representative papers on the theme were selected. The characteristic symptoms of CFD are hypertriglyceridemia—with or without hypocholesterolemia—and essential fatty acid deficiency. The principal CFD risk factors are pancreatic insufficiency, high-carbohydrate diet, liver diseases, inflammatory state and corticosteroid therapy. There are no specific recommendations regarding screening, which is typically performed based on the diagnosis, and at regular intervals, and more frequently in individuals belonging to high-risk groups. Treatment includes a balanced diet, micronutrient supplementation, and regular physical exercise according to individual tolerance. In the great majority of the cases, CFD-related hypertriglyceridemia does not reach values for which the use of hypolipidemic drugs is indicated. We conclude that there are few articles in the literature regarding the frequency, etiology and management of CFD. Preventive and therapeutic recommendations for hypertriglyceridemia are extrapolated from studies in individuals without cystic fibrosis. Further research is necessary to investigate the association of essential fatty acid deficiency and the physiopathology of cystic fibrosis . Since hypertriglyceridemia is an important risk factor for coronary artery disease, prospective studies will contribute for a better understanding of the natural history of this condition and define how to prevent and treat it.
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    ABSTRACT: Incidence of liver disease (LD) associated with cystic fibrosis (CF) and its clinical characterization still is unsettled. We have assessed prospectively the incidence and risk factors of this complication, and its impact on the clinical course of CF. Between 1980 and 1990, we enrolled 177 CF patients without LD in a systematic clinical, laboratory, ultrasonography screening program of at least a 10-year duration. During a 14-year median follow-up (2,432 patient-years), 48 patients developed LD, with cirrhosis already present in 5. Incidence rate (number of cases per 100 patient-years) was 1.8% (95% confidence interval: 1.3–2.4), with sharp decline after the age of 10 years and higher risk in patients with a history of meconium ileus (incidence rate ratio, 5.5; 2.7–11), male sex (2.5; 1.3–4.9), or severe mutations (2.4; 1.2–4.8) at multivariate analysis. Incidence of cirrhosis was 4.5% (2.3–7.8) during a median period of 5 years from diagnosis of liver disease. Among the 17 cirrhotic patients, 13 developed portal hypertension, 4 developed esophageal varices, 1 developed liver decompensation requiring liver transplantation. Development of LD did not condition different mortality (death rate ratio, 0.4; 0.1–1.5) or higher incidence of other clinically relevant outcomes. In conclusion, LD is a relatively frequent and early complication of CF, whose detection should be focused at the first life decade in patients with history of meconium ileus, male sex, or severe genotype. Although LD does not condition a different clinical course of CF, in some patients it may progress rapidly and require liver transplantation. (HEPATOLOGY2002;36:1374–1382).
    Hepatology 12/2002; 36(6):1374 - 1382. DOI:10.1002/hep.1840360613 · 11.19 Impact Factor
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