Failure of ursodeoxycholic acid to dissolve radiolucent gallstones in patients with cystic fibrosis

University of Milan, Milano, Lombardy, Italy
Acta Paediatrica (Impact Factor: 1.67). 06/1993; 82(6-7):562-5. DOI: 10.1111/j.1651-2227.1993.tb12754.x
Source: PubMed


Ursodeoxycholic acid has been used widely to dissolve cholesterol gallstones and more recently was shown to improve clinical symptoms and biochemical indices in different chronic liver diseases, including that associated with cystic fibrosis. We treated 10 cystic fibrosis patients (5 males, 5 females, age range 2-22 years) with pancreatic insufficiency and normal liver function with ursodeoxycholic acid 15-20 mg/kg/day. Seven patients had radiolucent gallstones (in 3 cases associated with biliary sludge) and 3 had sludge; all were asymptomatic. Before treatment, the gallbladder was well opacified in oral cholecystogram. The gallbladder was scanned by ultrasound in similar conditions and by the same operator before administration of ursodeoxycholic acid and after a median period of treatment of 16 months (range 11-32 months). During treatment, all patients remained asymptomatic and the relative proportion of ursodeoxycholic acid in duodenal bile increased from 4.7 +/- 3.2% at baseline to 34.7 +/- 8.6%. Complete or partial dissolution of gallstones was never observed and the maximum diameter of stones increased from a mean of 6.1 +/- 3.4 to 8.0 +/- 5.3 mm; in one case the development of biliary sludge occurred during bile acid therapy. Sludge disappeared in 1 of the 6 patients who initially had it, while in 2 cases its volume increased. We conclude that ursodeoxycholic acid is not effective in most CF patients with gallstones, probably because cholesterol is not the main component of stone or sludge.

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    • "UDCA can reduce cholesterol saturation in bile and progressively dissolve radiolucent cholesterol gallstones [24]. Such treatment has been well documented in adults [25], but only few authors give information about UDCA treatment effects in children [26] [27]. In our series only 6% of patients benefited from UDCA treatment. "
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    ABSTRACT: Aim of the study: Assessment of risk factors for cholelithiasis in pediatric population. Methods: A retrospective analysis of 143 patients with cholelithiasis treated during the period 2002-2012. Results: There was a significant female predilection for gallstones (73.4%). 70 (48.9%) children showed one or more risk factors for gallstones. 73 (51.1%) patients had no risk factors. Four groups of patients could be distinguished: 106 (74.3%) patients with colicky pain without jaundice, 10 patients with colicky pain with jaundice (7%), 16 (11.2%) children with pancreatitis, 8 (5.5%) with acute cholecystitis, and 3 patients with atypical symptoms (2%). According to therapy, patients could be divided in 3 groups: 130 children treated with laparoscopic cholecystectomy, 4 children treated with laparotomic cholecystectomy and 9 children treated with ursodeoxycholic acid. Conclusions: Laparoscopic cholecystectomy remains the golden standard in treatment for symptomatic cholelithiasis. Complications connected with laparoscopic cholecystectomy were noted in only 2% of patients in our series. Presence of relatives with cholelithiasis, obesity and hemolytic disorders were the predominant risk factors.
    Pediatria polska 07/2013; 88(4):335-339. DOI:10.1016/j.pepo.2013.06.003
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    • "Moreover, UDCA is not effective in cholesterol gall stone dissolution in cystic fibrosis patients [206]. Meta-analyses of UDCA in cystic fibrosis concluded that there was insufficient evidence to justify its routine use in cystic fibrosis [174,207]. "
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    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
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    ABSTRACT: Pathological processes and diseases of the upper gastrointestinal tract have become increasingly recognized over recent years as childhood entities responsible for a variety of upper gastrointestinal symptoms previously labelled as functional or non-organic. The term ‘dyspepsia’ is an adult one whose definition requires clarification before use in the paediatric context, but it encompasses age-dependent symptoms such as feedassociated irritability in the infant, peri-umbilical pain in the younger child, and heartburn, nausea, and indigestion in the older child as in adults. The possible organic conditions giving rise to such symptoms are multiple and multiorgan and include: gastro-oesophageal reflux; peptic ulcer disease; upper gastrointestinal Crohn's disease; antroduodenal motility disorders; pancreatitis; cholecystitis; cholelithiasis; biliary dyskinesia; and abdominal migraine. However, Munchausen syndrome by proxy must not be forgotten. Non-ulcer dyspepsia, it is now clear, has a basis in altered gastroduodenal motility and may be amenable to propulsion agents. In many individuals the dyspeptic symptoms of recurrent abdominal pain may be altered by psychotherapeutic intervention. Indeed there remains a proportion of children who undoubtedly have a behavioural or psychological base to their complaint. Nevertheless, with the recent increase in diagnostic yield from improved technical investigative aids available to paediatrics in the last 5–10 years, it is clear that the responsibility of the paediatrician to the child to find a cause of their symptoms is paramount. The variety of presenting features, possible causes of these symptoms, and appropriate investigation and treatment will be discussed, and management algorithms based on published literature and personal practice will be offered.
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