A two-year prospective study of the effect of ursodeoxycholic acid on urinary bile acid excretion and liver morphology in cystic fibrosis-associated liver disease

Lindblad, Anders; Glaumann, Hans; Strandvik, Birgitta

doi:10.1002/hep.510270126

Cited by 159 publications

(102 citation statements)

References 46 publications

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“…8 However, a more recent study showed good agreement between needle and wedge biopsies even in patients with CF, 28 and repeated needle biopsies in individual patients have shown similar morphology over time. 19,20 These studies suggest that liver biopsies might be as valuable in patients with CF as in patients with other liver diseases.…”

Section: Discussionmentioning

confidence: 99%

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Natural history of liver disease in cystic fibrosis

1999

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The median age of the population with cystic fibrosis (CF) has increased worldwide, which has led to the suggestion that the prevalence of liver disease would increase. The aim of this study was to evaluate the natural history of CF‐associated liver disease over a 15‐year period in a well‐controlled population of patients with CF. During the years 1976 through 1993, 124 patients were followed up by yearly liver function tests (LFTs). Fifteen patients were followed up with liver biopsies throughout the whole study period. More than 50% of the patients had pathological LFTs in infancy, later being normalized. Approximately 25% of children 4 years of age or older had biochemical markers of liver disease during the study period. In about 10% of the patients, cirrhosis or advanced fibrosis was confirmed at biopsy and 4% of patients had cirrhosis with clinical liver disease. Severe liver disease developed mainly during prepuberty and puberty. Of the 15 patients prospectively followed up with liver biopsies, only 3 had progressive fibrosis. No specific risk factor was identified, but deficiency of essential fatty acids was found more often in patients with marked steatosis (P < .05). No patient developed clinical liver disease in adulthood and the histological changes in the liver biopsies were usually not progressive. Liver disease was no more frequent at the end of the study period although the median age of the patient population had increased. Modern treatment might positively influence liver disease because it seemed less common, less progressive, and less serious than previously reported.

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Section: Discussionmentioning

confidence: 99%

“…The results of this study have recently been published. 20 Only the first biopsy before treatment with UDCA was evaluated in the present study.…”

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confidence: 99%

Natural history of liver disease in cystic fibrosis

1999

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“…13,41 Hepatobiliary disease in patients with CF primarily affects intrahepatic bile ductular cells rather than hepatocytes. 15,42 However, the effects of defective CFTR on biliary cells secretory function have not been studied as yet. We have addressed this issue in primary cultures of intrahepatic bile ductular cells isolated from control livers and from 1 patient with CF.…”

Section: Discussionmentioning

confidence: 99%

Correction of CFTR malfunction and stimulation of Ca2+-activated Cl− channels restore HCO3 − secretion in cystic fibrosis bile ductular cells

et al. 2002

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In view of the occurrence of hepatobiliary disorders in cystic fibrosis (CF) this study addresses the role of the cystic fibrosis transmembrane conductance regulator (CFTR) and of Ca 2؉ -activated Cl ؊ channels in promoting HCO 3 ؊ secretion in bile ductular cells. Human cholangiocytes were isolated from control livers and from 1 patient with CF (⌬F508/G542X mutations). Single channel and whole cell currents were analyzed by patch clamp techniques, and HCO 3 ؊ secretion was determined by fluorometric analysis of the rate of recovery of intracellular pH following alkaline loading. In control cholangiocytes, both cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) catalytic subunit, activated CFTR Cl ؊ channels that exhibited a nonrectifying conductance of 8 pS and appeared in clusters. Activation of Cl ؊ current by cAMP was associated with an increase in the rate of HCO 3 ؊ secretion. The basal rate of HCO 3 ؊ secretion was lower in CF than in control cholangiocytes. In both control and CF cholangiocytes, raising intracellular Ca 2؉ concentrations with ionomycin led to a parallel activation of Cl ؊ current and HCO 3 ؊ secretion. Consistent with reports that premature stop codon mutations (class I; e.g.,

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“…50 Histologic improvement has been reported as well. 51 However, the prognostic significance of these findings remains unclear. A higher dosage of UDCA (20 mg/kg/d) appears to be more effective than a lower dosage (10 mg/ kg/d) because the intestinal absorption of UDCA and, as a consequence, enrichment of bile with UDCA may be impaired when pancreatic insufficiency is present.…”

Section: Therapeutic Uses and Efficacymentioning

confidence: 99%