Ursodeoxycholic Acid

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Keith D Lindor - One of the best experts on this subject based on the ideXlab platform.

  • Ursodeoxycholic Acid therapy and liver transplant free survival in patients with primary biliary cholangitis
    Journal of Hepatology, 2019
    Co-Authors: Maren H Harms, Keith D Lindor, Henk R Van Buuren, Christophe Corpechot, Douglas Thorburn, Harry L A Janssen, Gideon M Hirschfield, Albert Pares
    Abstract:

    Background & Aims The clinical efficacy of Ursodeoxycholic Acid (UDCA) in primary biliary cholangitis (PBC) remains subject to debate as definitive randomized controlled trials are lacking. We aimed to determine whether UDCA prolongs liver transplant (LT)-free survival in patients with PBC. Methods This international cohort study included patients from the Global PBC Study Group database, originating from 8 countries in Europe and North America. Both UDCA-treated and untreated patients were included. LT and death were assessed as a combined endpoint through Cox regression analyses, with inverse probability treatment weighting (IPTW). Results In the 3,902 patients included, the mean (SD) age was 54.3 (11.9) years, 3,552 patients (94.0%) were female, 3,529 patients (90.4%) were treated with UDCA and 373 patients (9.6%) were not treated. The median (interquartile range) follow-up was 7.8 (4.1–12.1) years. In total, 721 UDCA-treated patients and 145 untreated patients died or underwent LT. After IPTW, the 10-year cumulative LT-free survival was 79.7% (95% CI 78.1–81.2) among UDCA-treated patients and 60.7% (95% CI 58.2–63.4) among untreated patients (p Conclusion The use of UDCA improves LT-free survival among patients with PBC, regardless of the disease stage and the observed biochemical response. These findings support UDCA as the current universal standard of care in PBC. Lay summary In this international multicenter study of 3,902 patients with primary biliary cholangitis, we found that treatment with Ursodeoxycholic Acid is associated with prolonged liver transplant-free survival. This association was significant, irrespective of sex, age, or disease stage. The survival benefit remained statistically significant in patients with an incomplete biochemical response to Ursodeoxycholic Acid therapy.

  • major hepatic complications in Ursodeoxycholic Acid treated patients with primary biliary cholangitis risk factors and time trends in incidence and outcome
    The American Journal of Gastroenterology, 2018
    Co-Authors: Maren H Harms, Pier Maria Battezzati, Keith D Lindor, Christophe Corpechot, Douglas Thorburn, Harry L A Janssen, Willem J Lammers, P Invernizzi, Frederik Nevens
    Abstract:

    Major Hepatic Complications in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis: Risk Factors and Time Trends in Incidence and Outcome

  • development and validation of a scoring system to predict outcomes of patients with primary biliary cirrhosis receiving Ursodeoxycholic Acid therapy
    Gastroenterology, 2015
    Co-Authors: Willem J Lammers, Keith D Lindor, Christophe Corpechot, Harry L A Janssen, Gideon M Hirschfield, Marlyn J Mayo, Frederik Nevens, Annarosa Floreani, Cyriel Y Ponsioen, Pietro Invernizzi
    Abstract:

    Background & Aims Approaches to risk stratification for patients with primary biliary cirrhosis (PBC) are limited, single-center based, and often dichotomous. We aimed to develop and validate a better model for determining prognoses of patients with PBC. Methods We performed an international, multicenter meta-analysis of 4119 patients with PBC treated with Ursodeoxycholic Acid at liver centers in 8 European and North American countries. Patients were randomly assigned to derivation (n = 2488 [60%]) and validation cohorts (n = 1631 [40%]). A risk score (GLOBE score) to predict transplantation-free survival was developed and validated with univariate and multivariable Cox regression analyses using clinical and biochemical variables obtained after 1 year of Ursodeoxycholic Acid therapy. Risk score outcomes were compared with the survival of age-, sex-, and calendar time-matched members of the general population. The prognostic ability of the GLOBE score was evaluated alongside those of the Barcelona, Paris-1, Rotterdam, Toronto, and Paris-2 criteria. Results Age (hazard ratio = 1.05; 95% confidence interval [CI]: 1.04−1.06; P P P P  = .0002); and platelet count (hazard ratio/10 units decrease=0.97; 95% CI: 0.96−0.99; P 0.30 had significantly shorter times of transplant-free survival than matched healthy individuals ( P Conclusions We developed and validated scoring system (the GLOBE score) to predict transplant-free survival of Ursodeoxycholic Acid−treated patients with PBC. This score might be used to select strategies for treatment and care.

  • efficacy of obeticholic Acid in patients with primary biliary cirrhosis and inadequate response to Ursodeoxycholic Acid
    Gastroenterology, 2015
    Co-Authors: Gideon M Hirschfield, Kris V Kowdley, Velimir A Luketic, Keith D Lindor, Catherine Vincent, Andrew L Mason, Stuart C Gordon, Marlyn J Mayo, Henry C Bodhenheimer
    Abstract:

    Background & Aims We evaluated the efficacy and safety of obeticholic Acid (OCA, α-ethylchenodeoxycholic Acid) in a randomized controlled trial of patients with primary biliary cirrhosis who had an inadequate response to Ursodeoxycholic Acid therapy. Methods We performed a double-blind study of 165 patients with primary biliary cirrhosis (95% women) and levels of alkaline phosphatase (ALP) 1.5- to 10-fold the upper limit of normal. Patients were randomly assigned to groups given 10 mg, 25 mg, or 50 mg doses of OCA or placebo, once daily for 3 months. Patients maintained their existing dose of Ursodeoxycholic Acid throughout the study. The primary outcome was change in level of ALP from baseline (day 0) until the end of the study (day 85 or early termination). We also performed an open-label extension of the trial in which 78 patients were enrolled and 61 completed the first year. Results OCA was superior to placebo in achieving the primary end point. Subjects given OCA had statistically significant relative reductions in mean ALP from baseline to the end of the study ( P P P P Conclusions Daily doses of OCA, ranging from 10 to 50 mg, significantly reduced levels of ALP, γ-glutamyl transpeptidase, and alanine aminotransferase, compared with placebo, in patients with primary biliary cirrhosis who had inadequate responses to Ursodeoxycholic Acid. The incidence and severity of pruritus were lowest among patients who received 10 mg/d OCA. Biochemical responses to OCA were maintained in a 12-month open-label extension trial. ClinicalTrials.gov ID: NCT00550862.

  • high dose Ursodeoxycholic Acid for the treatment of primary sclerosing cholangitis
    Hepatology, 2009
    Co-Authors: Keith D Lindor, Kris V Kowdley, Edwyn M Harrison, Denise M Harnois, Velimir A Luketic, Timothy M Mccashland, Alex S Befeler, Roberta A Jorgensen, Jan Petz, Jill C Keach
    Abstract:

    Primary sclerosing cholangitis (PSC) is a cholestatic liver disease that results in progressive fibrosis of intrahepatic and extrahepatic bile ducts. No effective therapy currently exists for this disease. Ursodeoxycholic Acid (UDCA), a hydrophilic bile Acid, is the most promising treatment option because of its benign side effect profile and documented benefit in the treatment of other cholestatic liver diseases, including primary biliary cirrhosis. Multiple studies using standard-dosage (8–15 mg/kg/d) and high-dosage (20–30 mg/kg/d) UDCA generally show improvement in liver chemistries in PSC patients, and several show improvement in liver histology. However, the majority of trials using UDCA in PSC are underpowered and fail to show improvements in clinically relevant endpoints, such as delayed progression to cirrhosis, portal hypertension, liver transplantation, development of cholangiocarcinoma, or death.

Gustav Paumgartner - One of the best experts on this subject based on the ideXlab platform.

  • mechanisms of action and therapeutic efficacy of Ursodeoxycholic Acid in cholestatic liver disease
    Clinics in Liver Disease, 2004
    Co-Authors: Gustav Paumgartner, Ulrich Beuers
    Abstract:

    Ursodeoxycholic Acid (UDCA) is widely used for the treatment of cholestatic liver diseases. Multiple mechanisms of action of UDCA have been described aiming at one or more of the pathogenetic processes of cholestatic liver diseases: (1) protection of injured cholangiocytes against toxic effects of bile Acids, (2) stimulation of impaired biliary secretion, (3) stimulation of detoxification of hydrophobic bile Acids, and (4) inhibition of apoptosis of hepatocytes. Through one or more of these mechanisms, UDCA slows the progression of primary biliary cirrhosis and improves a number of other cholestatic disorders.

  • Ursodeoxycholic Acid in cholestasis potential mechanisms of action and therapeutic applications
    Hepatology, 1998
    Co-Authors: M Ulrich D Beuers, James L Boyer, Gustav Paumgartner
    Abstract:

    ULRICH BEUERS,1 JAMES L. BOYER,2 AND GUSTAV PAUMGARTNER1 The dihydroxy bile Acid, Ursodeoxycholic Acid (UDCA), is increasingly used for the treatment of chronic cholestatic liver diseases. First reports of a beneficial effect on serum liver tests in cholestatic disorders were published in the 1980s in the Western literature,1-3 but similar observations had been made previously in Japan.4,5 Today, the therapeutic efficacy of UDCA has been shown for only one cholestatic disorder, primary biliary cirrhosis (PBC).6 The mechanism of action of UDCA in cholestasis has also not yet been clearly identified. Therefore, the aim of this article is to summarize clinical and experimental work that may help to clarify possible mechanisms of action of UDCA in cholestasis and provide a clearer rationale for the administration of UDCA in special cholestatic disorders.

  • Ursodeoxycholic Acid for treatment of primary sclerosing cholangitis a placebo controlled trial
    Hepatology, 1992
    Co-Authors: M Ulrich D Beuers, T Sauerbruch, U Spengler, Wolfgang Kruis, Ulker Aydemir, Baldur Wiebecke, W Heldwein, M Weinzierl, G R Pape, Gustav Paumgartner
    Abstract:

    The efficacy and safety of Ursodeoxycholic Acid for the treatment of primary sclerosing cholangitis were evaluated in a prospective, randomized, double-blind, placebo-controlled trial. Fourteen patients with primary sclerosing cholangitis documented by cholestatic serum enzyme pattern, liver histological appearance and endoscopic retrograde cholangiography were included in the trial. Six patients received Ursodeoxycholic Acid (13 to 15 mg/kg body wt/day), and eight patients received placebo. Two patients had to be withdrawn from the study, one because of UDCA-related diarrhea and the other because of worsening of the disease during placebo treatment. Patients in the Ursodeoxycholic Acid group improved significantly during 1 yr of treatment with respect to serum levels of bilirubin (median = -50%), alkaline phosphatase (median = -67%), gamma-glutamyltransferase (median = -53%), AST (median = -54%) and ALT (median = -36%) compared with the placebo group, but not with respect to serum levels of hydrophobic bile Acids. During Ursodeoxycholic Acid treatment, histopathological features also improved significantly, as evaluated by multiparametric score. Expression of human leukocyte antigen class I molecules appeared to be markedly reduced on liver cells after Ursodeoxycholic Acid treatment. We conclude that Ursodeoxycholic Acid is beneficial in reducing disease activity in patients with primary sclerosing cholangitis.

  • efficacy and safety of Ursodeoxycholic Acid for dissolution of gallstone fragments comparison with the combination of Ursodeoxycholic Acid and chenodeoxycholic Acid
    Hepatology, 1991
    Co-Authors: Michael Sackmann, Juergen Pauletzki, Uelker Aydemir, Joseph Holl, T Sauerbruch, Joerg Hasford, Gustav Paumgartner
    Abstract:

    A prospective, double-blind, randomized, single-center study was conducted to compare Ursodeoxycholic Acid alone with the combination of Ursodeoxycholic Acid and chenodeoxycholic Acid for dissolution therapy of gallstone fragments after shock wave lithotripsy. Patients with single radiolucent gallstones up to 30 mm in diameter or up to three stones of similar total volume received either 750 mg Ursodeoxycholic Acid alone (group A, n = 138) or the combination of 500 mg Ursodeoxycholic Acid and 500 mg chenodeoxycholic Acid (group B, n = 144) in a single bedtime dose. The bile Acids were administered from 2 wk before electrohydraulic lithotripsy until 3 mo beyond complete disappearance of all fragments. Patient's characteristics, stones (group A, 82% single stones, maximum diameter 19 +/- 5 mm, mean +/- S.D.; group B, 82% single stones, 18 +/- 5 mm), lithotripsy treatment and follow-up period were not different between the two groups. Between the two groups, no statistically significant difference was found in the time required for complete clearance of the fragments (group A, median time = 15 mo; group B, median time = 13 mo; p = 0.7). At 12 mo after lithotripsy, the probability of complete clearance was 46% +/- 5% in group A and 49% +/- 5% in group B. Diarrhea occurred significantly more often in group B than in group A (p less than 0.001) and was the main reason for withdrawal of randomized medication. Severe adverse effects of the bile Acids were not observed. It is concluded that monotherapy with Ursodeoxycholic Acid is as efficient as the combination of Ursodeoxycholic Acid and chenodeoxycholic Acid for fragment dissolution after lithotripsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Linda Scully - One of the best experts on this subject based on the ideXlab platform.

  • the canadian multicenter double blind randomized controlled trial of Ursodeoxycholic Acid in primary biliary cirrhosis
    Hepatology, 1994
    Co-Authors: Jenny E Heathcote, K Cauchdudek, Valery Walker, Robert J Bailey, Laurence M Blendis, Cameron N Ghent, Pina Michieletti, Gerald Y Minuk, Chris S Pappas, Linda Scully
    Abstract:

    Ursodeoxycholic Acid, a dihydroxyl bile Acid normally present in human beings in minimal amounts, becomes incorporated into the bile salt pool when taken orally. In cholestasis, bile Acids are retained in the liver and are hepatotoxic. Ursodeoxycholic Acid is the least-known hepatotoxic bile Acid, has choleretic properties and is reported to benefit patients with chronic cholestasis. In a nationwide Canadian controlled trial, 222 patients with primary biliary cirrhosis were treated with Ursodeoxycholic Acid (14 mg/kg/body wt/day) or placebo for 24 mo. Only patients with a diagnosis confirmed by liver biopsy and serum positive for antimitochondrial antibodies were enrolled; 88% were symptomatic on entry. The primary outcome measure was percent change in total serum bilirubin from baseline to final follow-up. Treated patients (111) and controls (111) were comparable with regard to age, gender, biochemical parameters and liver histological condition. Although treatment was not associated with any improvement in symptoms, Ursodeoxycholic Acid therapy caused the bilirubin to fall significantly within the first 3 mo of therapy (p < 0.001). Significant falls in serum alkaline phosphatase, aminotransferases, cholesterol and IgM levels were also noted in the treated group. Improvement in some histological features was observed but there was no difference between the groups in the number of patients who reached the endpoints of death or liver transplantation. Ursodeoxycholic Acid, given to patients with primary biliary cirrhosis, leads to an improvement in serum markers of cholestasis. A larger sample size is needed to determine whether Ursodeoxycholic Acid therapy has a beneficial effect on the survival of patients with primary biliary cirrhosis.

  • the canadian multicenter double blind randomized controlled trial of Ursodeoxycholic Acid in primary biliary cirrhosis
    Hepatology, 1994
    Co-Authors: Jenny E Heathcote, K Cauchdudek, Valery Walker, Robert J Bailey, Laurence M Blendis, Cameron N Ghent, Pina Michieletti, Gerald Y Minuk, Chris S Pappas, Linda Scully
    Abstract:

    Ursodeoxycholic Acid, a dihydroxyl bile Acid normally present in human beings in minimal amounts, becomes incorporated into the bile salt pool when taken orally. In cholestasis, bile Acids are retained in the liver and are hepatotoxic. Ursodeoxycholic Acid is the least-known hepatotoxic bile Acid, has choleretic properties and is reported to benefit patients with chronic cholestasis. In a nationwide Canadian controlled trial, 222 patients with primary biliary cirrhosis were treated with Ursodeoxycholic Acid (14 mg/kg/body wt/day) or placebo for 24 mo. Only patients with a diagnosis confirmed by liver biopsy and serum positive for antimitochondrial antibodies were enrolled; 88% were symptomatic on entry. The primary outcome measure was percent change in total serum bilirubin from baseline to final follow-up. Treated patients (111) and controls (111) were comparable with regard to age, gender, biochemical parameters and liver histological condition. Although treatment was not associated with any improvement in symptoms, Ursodeoxycholic Acid therapy caused the bilirubin to fall significantly within the first 3 mo of therapy (p<0.001). Significant falls in serum alkaline phosphatase, aminotransferases, cholesterol and IgM levels were also noted in the treated group. Improvement in some histological features was observed but there was no difference between the groups in the number of patients who reached the endpoints of death or liver transplantation. Ursodeoxycholic Acid, given to patients with primary biliary cirrhosis, leads to an improvement in serum markers of cholestasis. A larger sample size is needed to determine whether Ursodeoxycholic Acid therapy has a beneficial effect on the survival of patients with primary biliary cirrhosis. (HEPATOLOGY 1994;19:1149–1156.)

Kris V Kowdley - One of the best experts on this subject based on the ideXlab platform.

  • efficacy of obeticholic Acid in patients with primary biliary cirrhosis and inadequate response to Ursodeoxycholic Acid
    Gastroenterology, 2015
    Co-Authors: Gideon M Hirschfield, Kris V Kowdley, Velimir A Luketic, Keith D Lindor, Catherine Vincent, Andrew L Mason, Stuart C Gordon, Marlyn J Mayo, Henry C Bodhenheimer
    Abstract:

    Background & Aims We evaluated the efficacy and safety of obeticholic Acid (OCA, α-ethylchenodeoxycholic Acid) in a randomized controlled trial of patients with primary biliary cirrhosis who had an inadequate response to Ursodeoxycholic Acid therapy. Methods We performed a double-blind study of 165 patients with primary biliary cirrhosis (95% women) and levels of alkaline phosphatase (ALP) 1.5- to 10-fold the upper limit of normal. Patients were randomly assigned to groups given 10 mg, 25 mg, or 50 mg doses of OCA or placebo, once daily for 3 months. Patients maintained their existing dose of Ursodeoxycholic Acid throughout the study. The primary outcome was change in level of ALP from baseline (day 0) until the end of the study (day 85 or early termination). We also performed an open-label extension of the trial in which 78 patients were enrolled and 61 completed the first year. Results OCA was superior to placebo in achieving the primary end point. Subjects given OCA had statistically significant relative reductions in mean ALP from baseline to the end of the study ( P P P P Conclusions Daily doses of OCA, ranging from 10 to 50 mg, significantly reduced levels of ALP, γ-glutamyl transpeptidase, and alanine aminotransferase, compared with placebo, in patients with primary biliary cirrhosis who had inadequate responses to Ursodeoxycholic Acid. The incidence and severity of pruritus were lowest among patients who received 10 mg/d OCA. Biochemical responses to OCA were maintained in a 12-month open-label extension trial. ClinicalTrials.gov ID: NCT00550862.

  • high dose Ursodeoxycholic Acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis
    The American Journal of Gastroenterology, 2011
    Co-Authors: John E. Eaton, Kris V Kowdley, Edwyn M Harrison, Marina G Silveira, Darrell S Pardi, Emmanouil Sinakos, Velimir A Luketic, Timothy M Mccashland, Alex S Befeler, Denise M Harnois
    Abstract:

    High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

  • high dose Ursodeoxycholic Acid for the treatment of primary sclerosing cholangitis
    Hepatology, 2009
    Co-Authors: Keith D Lindor, Kris V Kowdley, Edwyn M Harrison, Denise M Harnois, Velimir A Luketic, Timothy M Mccashland, Alex S Befeler, Roberta A Jorgensen, Jan Petz, Jill C Keach
    Abstract:

    Primary sclerosing cholangitis (PSC) is a cholestatic liver disease that results in progressive fibrosis of intrahepatic and extrahepatic bile ducts. No effective therapy currently exists for this disease. Ursodeoxycholic Acid (UDCA), a hydrophilic bile Acid, is the most promising treatment option because of its benign side effect profile and documented benefit in the treatment of other cholestatic liver diseases, including primary biliary cirrhosis. Multiple studies using standard-dosage (8–15 mg/kg/d) and high-dosage (20–30 mg/kg/d) UDCA generally show improvement in liver chemistries in PSC patients, and several show improvement in liver histology. However, the majority of trials using UDCA in PSC are underpowered and fail to show improvements in clinically relevant endpoints, such as delayed progression to cirrhosis, portal hypertension, liver transplantation, development of cholangiocarcinoma, or death.

  • Ursodeoxycholic Acid therapy in hepatobiliary disease
    The American Journal of Medicine, 2000
    Co-Authors: Kris V Kowdley
    Abstract:

    Ursodeoxycholic Acid is a hydrophilic bile Acid that under normal circumstances represents a small fraction of the bile Acid pool in humans. It is effective in dissolving cholesterol gallstones in appropriately selected patients. Ursodeoxycholic Acid improves serum alkaline phosphatase and aminotransferase levels in primary biliary cirrhosis, but its effects on rates of liver transplantation and death are less certain. Ursodeoxycholic Acid has no promising effects in several other cholestatic liver diseases, such as cystic fibrosis and intrahepatic cholestasis of pregnancy, but data are too preliminary to make recommendations about its routine use in these conditions. Its effects are mediated by amelioration of damage to cell membranes caused by retained toxic bile Acids. Ursodeoxycholic Acid improves biliary secretion of bile Acids, may improve bile flow, and it has immunomodulatory properties that may reduce immune-mediated liver damage. However, its use in the treatment of cholestatic liver disease remains uncertain pending additional randomized trials.

Denise M Harnois - One of the best experts on this subject based on the ideXlab platform.

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