Prediction of liver failure in cirrhotic primary biliary cholangitis patients under obeticholic acid in Hepatology
2021
AOU Città della Salute di Torino
Tipo pubblicazione
Conference Abstract
Autori/Collaboratori (49)Vedi tutti...
Carbone M
Vespasiani-Gentilucci U
Izzi A
et alii...
Abstract
Background: The U.S. Food and Drug Administration (FDA) has recently restricted the use of obeticholic acid (OCA) in patients with primary biliary cholangitis (PBC) with 'advanced cirrhosis' because in this patient category it has a narrow therapeutic index and can precipitate liver failure. In this study we attempted to better define the safety threshold in cirrhotic patients undertaking OCA as second line therapy, and we explored predicting factors of treatment failure and liver decompensation after OCA. Methods: Efficacy and safety of 12 month of OCA treatment were evaluated in a cohort of consecutively recruited cirrhotic patients from the Italian PBC Registry. All patients who had received at least one dose of OCA and had at least 12 months of follow-up constituted the overall cohort (OC), and those completing the treatment period of 6 or 12 months for the analysis at 6 or 12 months, respectively, constituted the Treatment Completer Cohort (TCC). Response to OCA therapy was evaluated according to the Poise criteria. Risk factors for nonresponse and for occurrence of liver decompensation were reported as risk ratios (RR) with 95% confidence intervals (CIs). Results: One hundred PBC cirrhotic patients (median age 62 years, 95% women) were included in the analyses (97 Child-Pugh A, 3 Child-Pugh B). Thirty-one patients had esophageal varices and 5 had ascites at baseline. According to Poise criteria, 33% and 32% of patients achieved a biochemical response at 6 and 12 months, respectively, in the OC population, and 35.5% and 41% in the TCC population. Male sex (aRR 1.75, 95%CI 1.42-2.12), INR (1.37, 95%CI 1.00-1.87), Child-Pugh score (1.79, 95%CI 1.28-2.50), MELD (1.17, 95%CI 1.04-1.30), and total bilirubin (1.83 95%CI 1.11-3.01) were independently associated with nonresponse to OCA. Twenty-two patients discontinued OCA treatment before 12 months, 10 due to pruritus. Nine patients discontinued OCA for liver decompensation (6 for worsening of liver function; 3
DOI : 10.1002/hep.32188
Keywords
risk factor; primary biliary cirrhosis; pruritus; prediction; pharmacokinetics; middle aged; liver function; major clinical study; male; liver failure; lack of drug effect; international normalized ratio; human; human tissue; follow up; female; drug therapy; esophagus varices; drug safety; drug efficacy; decompensated liver cirrhosis; conference abstract; controlled study; cohort analysis; clinical assessment; Child Pugh score; bleeding; ascites; bilirubin blood level; adult; albumin level; obeticholic acid; bilirubin;