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.
"Moreover, UDCA is not effective in cholesterol gall stone dissolution in cystic fibrosis patients . Meta-analyses of UDCA in cystic fibrosis concluded that there was insufficient evidence to justify its routine use in cystic fibrosis [174,207]. "
[Show abstract][Hide abstract] ABSTRACT: Ursodeoxycholic acid (UDCA) is a steroid bile acid approved for primary biliary cirrhosis (PBC). UDCA is reported to have "hepato-protective properties". Yet, UDCA has "unanticipated" toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively). "Unanticipated" UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day) and toxic dose (28 mg/kg/day), and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified.
International Journal of Molecular Sciences 07/2012; 13(7):8882-914. DOI:10.3390/ijms13078882 · 2.86 Impact Factor
"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. "
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] 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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