Ursodeoxycholic acid therapy in cystic fibrosis—associated liver disease: A dose-response study

Abstract

Previous studies from our groups have demonstrated improvements in biochemical markers of liver function when cystic fibrosis patients with associated liver disease were administered oral ursodeoxycholic acid. The magnitude of the response was somewhat less than that found when comparable doses (10 to 15 mg/kg body wt/day) of ursodeoxycholic acid are given to other liver disease patients; this may be explained by the bile acid malabsorption that is characteristic of the disease. For this reason a dose-response study was carried out in nine cystic fibrosis patients with liver disease to establish whether improved efficacy could be obtained with higher doses. Ursodeoxycholic acid in doses of 5, 10 and 15 mg/kg body wt/day was given orally for consecutive 2-mo periods in a replicated Latin-square design. After this, all patients received 20 mg/kg body wt/day. Liver function, individual serum bile acids and biliary bile acid composition were determined at entry and at the end of each treatment period. Our data demonstrate that the magnitude of the biochemical improvement in serum liver enzymes was significantly greater with higher doses of ursodeoxycholic acid; at 20 mg/kg body wt/day it was similar to that reported for patients with other liver diseases administered lower doses. Biliary ursodeoxycholic acid enrichment increased with increasing doses, attaining 42% +/- 6% of the total biliary bile acids with the highest dose. Fasting serum ursodeoxycholic acid concentrations increased during ursodeoxycholic acid administration but were variable and correlated poorly with the dose of ursodeoxycholic acid administered, whereas no correlation was found between serum ursodeoxycholic acid concentration and the proportion of ursodeoxycholic acid in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…UDCA has been shown to increase in the duodenal bile up to an average of 42% of total bile acids, the increase being about 28% when a dose similar to the one in the present study was given. 27 The UDCA fraction in urine varied between 7% and 77%, but the two patients who did not normalize LFT had high levels of UDCA in urine, both in relative (64% and 70%) and absolute concentrations compared with the other patients. Case 7, who was one of the most affected patients regarding liver disease, and did not respond to the treatment, had a high UDCA concentration in urine (18% vs. Ͻ5% in all other patients) at the start of the study.…”

Role for Membrane Fluidity in Ethanol-Induced Oxidative Stress of Primary Rat Hepatocytes

“…In our study, UDCA and GM1 actions, at the doses used in our experiments, cannot be attributed to direct antioxidant properties of these compounds since they were unable to scavenge superoxide anion and hydroxyl radical in vitro and to inhibit iron-induced lipid peroxidation of rat hepatocytes. This new mechanistic demonstration of a beneficial effect of UDCA is particularly interesting because UDCA is a therapeutically relevant bile acid, already used for preventing human chronic cholestatic liver diseases (Colombo et al, 1992;Poupon et al, 2003) that might be useful in the very early stages of the alcoholic liver diseases as well.…”

Tratamientos de la colestasis crónica en niños

“…Al cabo de dos meses de tratamiento con AUDC, la presencia de este ácido biliar representa entre el 25 y el 42% de la reserva, a expensas de los ácidos cólico y quenodesoxicólico; estas diferencias son dependientes de la dosis [9] . A partir de estos estudios se llegó a la conclusión de que la dosificación recomendada de AUDC es de 20 mg/kg/día o mayor [9] .…”