Effects of ursodeoxycholic acid on liver function in patients with cystic fibrosis and chronic cholestasis

doi:10.1016/S0022-3476(05)82561-2

The Journal of Pediatrics

Volume 121, Issue 1, July 1992, Pages 138-141

https://doi.org/10.1016/S0022-3476(05)82561-2 Get rights and content

Ursodeoxycholic acid, 10 to 20 mg/kg per day, was administered for 1 year to 22 patients with cystic fibrosis and chronic cholestasis, resulting in significantly improved liver enzyme values. However, evidence of cholestasis continued, as shown by the pattern of alkaline phosphatase isoenzymes.

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Cited by (66)

Study of quality and stability of ursodeoxycholic acid formulations for oral pediatric administration
2014, International Journal of Pharmaceutics
Citation Excerpt :
UDCA has been used in infants and children with different pathologies: hepatic and biliary cholestasis, as adjuvant therapy (Balisteri, 1997), management of biliar atresia (Ullrich et al., 1987), and the treatment of parenteral nutrition-associated cholestasis (De Marco et al., 2006). The recommended UDCA dose for children is 5–30 mg/kg/day divided into two or three doses (Galabert et al., 1992; Arslanoglu et al., 2008). UDCA is available depending on the country as commercial capsules (150–500 mg) or tablets (150–500 mg) (Vademecum, 2010).
This paper describes a rational method of characterizing the biopharmaceutical stability of two oral suspensions of ursodeoxycholic acid (UDCA) used in pediatrics. Because there is no commercial presentation of UDCA that can administer appropriate doses for infants and children, an active pharmaceutical ingredient (API) formulation is required. Due to its very low solubility and low dose in the formula (1.5%), two different suspensions with minimal use of excipients were studied, avoiding the use of complex additives and those not recommended by the European Medicines Agency (EMA). Adherence to Standard Operating Procedure (SOP) allows the preparation of formulations with appropriately sized and stable particles, and suitable rheological behavior in withdrawing the dose after stirring. Dose uniformity, expressed as mass and content variability, was determined using the criteria of the European and the United States Pharmacopoeia. Additionally, dose content variation of every mass determined was studied. A rational method was developed for determining the dose uniformity of UDCA in suspensions, whether freshly prepared or after storage under different conditions for 30 and 60 days. This method permits detection of differences between doses taken at different heights in the vessel at various times and storage conditions. UDCA was stable under all conditions studied, requiring the presence of glycerol in the formulation to obtain the declared API value after stirring. Storage of UDCA suspensions in a refrigerator increased variability between doses.
Liver disease in cystic fibrosis
2014, Paediatric Respiratory Reviews
Citation Excerpt :
Treatment with UDCA can be started as soon as the diagnosis of CFLD is made at a dose of 20 mg/kg/day. UDCA has been shown to improve AST and ALT, bile drainage, liver histology as well as nutritional status and general condition.54–59 However, there is no evidence that UDCA treatment changes the natural history of liver disease and its routine use in CF is not recommended.60
The survival of patients with cystic fibrosis (CF) has progressively increased over recent decades, largely attributable to early diagnosis through newborn screening and advances in nutritional and respiratory care. As the life expectancy of patients with CF has improved, non-respiratory complications such as liver disease have become increasingly recognized.
Biochemical derangements of liver enzymes in CF are common and may be attributed to a number of specific hepatobiliary abnormalities. Among them, Cystic Fibrosis-associated Liver Disease (CFLD) is clinically the most significant hepatic complication and is believed to have a significant impact on morbidity and mortality. However, there remains much conjecture about the extent of the adverse prognostic implications that a diagnosis of CFLD has on clinical outcomes. The purpose of this review is to give an overview of the current knowledge regarding liver disease in children with CF.
Ursodeoxycholic acid treatment in patients with cystic fibrosis at risk for liver disease
2010, Digestive and Liver Disease
Citation Excerpt :
Since a negative prognostic impact of CFLD has been related to impairment of pulmonary function and nutritional status [9–11], therapeutic approaches have been proposed. Currently ursodeoxycholic acid (UDCA) appears to be the only beneficial therapy able to prevent the progression of CFLD, as previously described [12–18]. It has been reported that long-term UDCA therapy may improve biochemical and ultrasound indices of liver function [12,18–20].
Meconium ileus has been detected as a risk factor for development of liver disease in cystic fibrosis, with influence on morbidity and mortality.
To evaluate the effect of early treatment with ursodeoxycholic acid in patients with cystic fibrosis and meconium ileus to prevent chronic hepatic involvement and to explore the potential role of therapy on clinical outcomes.
26 cystic fibrosis patients with meconium ileus (16 M, mean age 8,4 years, range 3,5–9) were assigned to two groups: group 1 (14 patients) treated early with ursodeoxycholic acid (UDCAe); group 2 (12 patients) treated with ursodeoxycholic acid at the onset of cystic fibrosis liver disease (UDCAd). Anthropometric data, pulmonary function tests, pancreatic status, complications such as diabetes, hepatic involvement and Pseudomonas aeruginosa colonisation were compared among groups.
A higher prevalence of cystic fibrosis chronic liver disease was observed in the UDCAd group with a statistically significant difference at 9 years of age (p < 0.05). Chronic infection by P. aeruginosa was found in 7% of UDCAe and 33% of UDCAd (p < 0.05). No differences were observed in nutritional status and other complications.
Early treatment with ursodeoxycholic acid may be beneficial in patients at risk of developing cystic fibrosis chronic liver disease such as those with meconium ileus. Multicentre studies should be encouraged to confirm these data.
Cystic Fibrosis: A Review of Epidemiology and Pathobiology
2007, Clinics in Chest Medicine
Citation Excerpt :
This type of disease is usually diagnosed at median age 9 to 10 years [43,44] and progresses over time. No treatment has been shown to delay the progression of disease, but because it can be fatal, ursodeoxycholic acid, which improves the biochemical profile of liver disease, is often administered [45]. Liver disease was listed as the primary cause of death in 2.5% of deaths in patients who have CF, which places it as the second most common cause of death [24].
Improvements in outcomes for patients who have cystic fibrosis (CF) have been striking in the last 30 years. Median survival now approaches the fifth decade of life. Advances in the understanding of the basic defect and the pathobiology of CF have led to new treatments, some of which have undoubtedly contributed to this success. Improved understanding of the basic defect and the acquisition and maintenance of epidemiologic resources for the CF population in the United States have allowed us to determine predictors of survival and identify genetic, environmental, and therapeutic factors that may influence it. This article reviews some of the key epidemiologic and pathobiologic factors discovered thus far.
Treatment of Hereditary Hemochromatosis, Wilson Disease, and Other Metabolic Disorders of the Liver
2006, Therapy of Digestive Disorders
Treatment of hereditary hemochromatosis, Wilson disease, and other metabolic disorders of the liver
2005, Therapy of Digestive Disorders, Second Edition

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^†: Supported by grants from the Association Française de Lutte contre la Mucoviscidose and the Caisse Régionale d Assurance Maladie du Sud-Est.

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Clinical and laboratory observationEffects of ursodeoxycholic acid on liver function in patients with cystic fibrosis and chronic cholestasis†

J Pediatr

Clin Chim Acta

Gastroenterology

Gastroenterology

J Pediatr

Clinical and laboratory observation
Effects of ursodeoxycholic acid on liver function in patients with cystic fibrosis and chronic cholestasis†