Effects of ursodeoxycholic acid therapy for liver disease associated with cystic fibrosis

Colombo, Carla; Setchell, Kenneth D.R.; Podda, Mauro; Crosignani, Andrea; Roda, Aldo; Curcio, L; Ronchi, M; Giunta, Annamaria

doi:10.1016/s0022-3476(05)81103-5

Cited by 133 publications

(62 citation statements)

References 33 publications

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“…[7][8][9][10][11][12][23][24][25] The mechanism of action of UDCA in hepatobiliary diseases is still not completely understood. 26 -38 Decreased intestinal absorption of hydrophobic, hepatotoxic bile acids, 39,40 and biliary enrichment with hydrophilic, nontoxic UDCA changes the balance of biliary bile acids in favor of nontoxic hydrophilic bile acids, and this change may represent one of the mechanisms of action of UDCA.…”

Section: Discussionmentioning

confidence: 99%

Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis

et al. 2004

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Ursodeoxycholic acid (UDCA) has beneficial effects in cholestatic liver diseases. In primary sclerosing cholangitis (PSC), there is evidence that high doses (؎20 mg/kg) of UDCA may be more effective than average doses. Biliary enrichment of UDCA at such high doses may represent the decisive factor for its beneficial effect. Up to now it is not clear how high-dose UDCA correlates with its biliary enrichment and whether bacterial degradation of large amounts of UDCA may lead to an increased bacterial formation of more toxic hydrophobic bile acids. We determined the biliary bile acid composition in 56 patients with PSC including 30 patients with repeat bile samples treated with various doses of UDCA. At a UDCA dose of 10 -13 mg/kg/d (n ‫؍‬ 18) biliary UDCA represented 43.1% ؉ 0.3% (mean ؉ SD) of total bile acids; at a UDCA dose of 14 -17 mg/kg (n ‫؍‬ 14), its biliary content increased to 46.9% ؉ 0.3%, at 18 -21 mg/kg (n ‫؍‬ 34) to 55.9% ؉ 0.2%, at 22-25 mg/kg (n ‫؍‬ 12) to 58.6% ؉ 2.3%, and at 26 -32 mg/kg (n ‫؍‬ 8) to 57.7% ؉ 0.4%. During UDCA treatment, the biliary content of all other bile acids was unchanged or decreased. In conclusion, biliary enrichment of UDCA increases with increasing dose and reaches a plateau at 22-25 mg/kg. There was no increase of toxic hydrophobic bile acids. If biliary enrichment of UDCA represents the decisive factor for its clinical effect, it seems likely that UDCA doses of up to 22-25 mg/kg may be more effective than lower doses. (HEPATOLOGY 2004;40:693-698.)

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Section: Discussionmentioning

confidence: 99%

Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis

et al. 2004

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“…Several pilot studies have shown that UDCA is responsible for an improvement in biochemical tests, mainly a decrease in serum levels of aminotransferases (ALT and AST) and ␥ -glutamyl transferase (GGT) [11] . In addition, liver inflammation and/or bile duct proliferation were improved after 2 years of UDCA therapy in control biopsies.…”

Section: Cystic Fibrosismentioning

confidence: 99%

Treatments in Chronic Cholestasis in Children

Álvarez¹

2008

Ann Nestlé [Engl]

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Few specific treatments for children with chronic cholestasis are available. Most therapy strategies relieve bile component retention or palliate some of the consequences of chronic cholestasis. Ursodeoxycholic acid is the most frequently used pharmacological agent in children with chronic cholestasis. This bile acid is administered at dosages between 10 and 30 mg/kg/day to patients with cystic fibrosis, inborn errors of bile acid metabolism, progressive familial intrahepatic cholestasis, sclerosing cholangitis, biliary atresia, Alagille syndrome, or those receiving total parenteral nutrition. Ursodeoxycholic acid mainly increases bile flow and has a membrane-stabilizing effect, reducing the toxicity of more hydrophobic bile acids. Rifampicin, an antibiotic, at dosages between 10 and 20 mg/kg/day is very efficient in relieving pruritus. Similar effects are obtained using nonabsorbable ion exchange resins. In addition, these molecules decrease the serum cholesterol levels contributing to reduce xanthomas. Replacement of some deficiencies created by total parenteral nutrition by administration of essential fatty acids or cysteine can prevent or contribute to improve the associated liver disorders. In some cholestatic diseases, surgical procedures can help to relieve the obstacle to the bile flow, as it is the case for portoenterostomy in patients with biliary atresia. In cases of intrahepatic cholestasis, a clinical and biochemical improvement can be recorded after bile diversion or other procedure (ileum exclusion) limiting the absorption of bile acids by the intestine. In the future, the association of these different pharmacological agents, increasing the bile flow, protecting cell membranes, or restoring nutritional deficiencies, could contribute to an improvement in quality of life in children with chronic cholestasis and eventually delay the need of a more drastic therapy such as liver transplantation. Advances in gene therapy and hepatocyte transplantation could also be of great help; however, many years of intense research are still necessary before even a pilot study using one of these therapies can be considered on liver diseases resulting in chronic cholestasis.

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“…En varios estudios piloto se ha observado que el AUDC es responsable de una mejoría en las pruebas bioquímicas, principalmente una reducción de los niveles séricos de aminotransferasas (ALT y AST) y ␥ -glutamiltransferasa (GGT) [11] . Además, en las biopsias de control mejoraron la inflamación hepática y/o la proliferación de conductos biliares al cabo de 2 años de tratamiento con AUDC.…”

Section: Fibrosis Quísticaunclassified

Tratamientos de la colestasis crónica en niños

Álvarez¹

2008

Ann Nestlé [Esp]

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Se dispone de pocos tratamientos específicos para los niños con colestasis crónica. La mayoría de las estrategias terapéuticas alivian la retención de componentes de la bilis o aminoran algunas de las consecuencias de la colestasis crónica. El ácido ursodesoxicólico es el fármaco que con más frecuencia se utiliza en niños con colestasis crónica. Este ácido biliar se administra a la dosis de 10 a 30 mg/kg/día en pacientes con fibrosis quística, errores congénitos del metabolismo de los ácidos biliares, colestasis intrahepática familiar progresiva, colangitis esclerosante, atresia biliar, síndrome de Alagille o a aquéllos tratados con nutrición parenteral total. El ácido ursodesoxicólico incrementa principalmente el flujo de bilis y posee un efecto estabilizador de la membrana reduciendo la toxicidad de los ácidos biliares más hidrofóbicos. La rifampicina, un antibiótico, a una dosis entre 10 y 20 mg/kg/día, es muy eficaz en el alivio del prurito. Se obtienen efectos similares utilizando resinas intercambiadoras de iones no absorbibles. Además, estas moléculas disminuyen los niveles séricos de colesterol contribuyendo a reducir los xantomas. La sustitución de algunas carencias generadas por la nutrición parenteral total mediante la administración de ácidos grasos esenciales o cisteína puede evitar los trastornos hepáticos asociados o contribuir a mejorarlos. En algunas enfermedades colestáticas, las intervenciones quirúrgicas pueden ayudar a aliviar el obstáculo frente al flujo de bilis, como es el caso de la portoenterostomía en pacientes con atresia biliar. En casos de colestasis interhepática, puede registrarse una mejoría clínica y bioquímica tras una derivación de la bilis u otra intervención (exclusión del íleon), que limita la absorción de ácidos biliares en el intestino. En el futuro, la asociación de estos diferentes agentes farmacológicos, que incrementan el flujo de bilis, protegen las membranas celulares o restablecen las carencias nutricionales, podría contribuir a mejorar la calidad de vida en niños con colestasis crónica y retrasar en última instancia la necesidad de un tratamiento más drástico como el trasplante hepático. También podrían ser de gran ayuda los progresos en la terapia génica y el trasplante de hepatocitos; no obstante, todavía son necesarios muchos años de investigación intensiva antes de que pueda considerarse incluso un estudio piloto que utilice uno de estos tratamientos en hepatopatías inductoras de colestasis crónica.

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Effects of ursodeoxycholic acid therapy for liver disease associated with cystic fibrosis

Cited by 133 publications

References 33 publications

Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis

Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis

Treatments in Chronic Cholestasis in Children

Tratamientos de la colestasis crónica en niños

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