Predictors of serious adverse events and non‐response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid
Authors: De Vincentis Antonio , D'Amato Daphne , Cristoferi Laura , Gerussi Alessio , Malinverno Federica , Lleo Ana , Colapietro Francesca , Marra Fabio , Galli Andrea , Fiorini Cecilia , Coco Barbara , Brunetto Maurizia , Niro Grazia Anna , Cotugno Rosa , Saitta Carlo , Cozzolongo Raffaele , Losito Francesco , Giannini Edoardo Giovanni , Labanca Sara , Marzioni Marco , Marconi Giulia , Morgando Anna , Pellicano Rinaldo , Vanni Ester , Cazzagon Nora , Floreani Annarosa , Chessa Luchino , Morelli Olivia , Muratori Luigi , Pellicelli Adriano , Pompili Maurizio , Ponziani Francesca , Tortora Annalisa , Rosina Floriano , Russello Maurizio , Cannavò Mariarita , Simone Loredana , Storato Silvia , Viganò Mauro , Abenavoli Ludovico , D'Antò Maria , De Gasperi Elisabetta , Distefano Marco , Scifo Gaetano , Zolfino Teresa , Calvaruso Vincenza , Cuccorese Giuseppe , Palitti Valeria Pace , Sacco Rodolfo , Bertino Gaetano , Frazzetto Evelise , Alvaro Domenico , Mulinacci Giacomo , Palermo Andrea , Scaravaglio Miki , Terracciani Francesca , Galati Giovanni , Ronca Vincenzo , Zuin Massimo , Claar Ernesto , Izzi Antonio , Picardi Antonio , Invernizzi Pietro , Vespasiani‐Gentilucci Umberto , Carbone Marco ,   on behalf of the Club Epatologi Ospedalieri (CLEO)/Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) PBC Study Group and, the Italian PBC Registry
Published: August 2022

Background & Aims

Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with “advanced cirrhosis” because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non‐response in cirrhotic patients undergoing OCA therapy.

Methods

Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non‐response were reported as risk ratios (RR) with 95% confidence intervals (CIs).

Results

One hundred PBC cirrhotics were included, 97 Child‐Pugh class A and 3 class B. Thirty‐one had oesophageal varices and 5 had a history of ascites. Thirty‐three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted‐RR 1.75, 95%CI 1.42–2.12), INR (1.37, 1.00–1.87), Child‐Pugh score (1.79, 1.28–2.50), MELD (1.17, 1.04–1.30) and bilirubin (1.83, 1.11–3.01) were independently associated with non‐response to OCA. Twenty‐two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted‐RR 1.91, 95%CI 1.10–3.36), lower albumin levels (0.18, 0.06–0.51), Child‐Pugh score (2.43, 1.50–4.04), history of ascites (3.5, 1.85–6.5) and bilirubin (1.30, 1.05–1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA.

Conclusions

An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use.