Author information

Collaborators

• on behalf of the Club Epatologi Ospedalieri (CLEO)/Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) PBC Study Group and, the Italian PBC Registry: 

Valentina Feletti, Alessandro Mussetto, Rosanna Venere, Giulia Bernaccioni, Marie Graciella Pigozzi, Stefano Fagiuoli, Natalia Terreni, Pietro Pozzoni, Leonardo Baiocchi, Giuseppe Grassi, Maria Vinci, Valentina Bellia, Roberto Boldizzoni, Silvia Casella, Barbara Omazzi, Guido Poggi

Affiliations

• ¹Internal Medicine and Hepatology, University Campus Bio-Medico of Rome, Rome, Italy.
• ²Gastroenterology Unit, Città della salute e della scienza, Turin, Italy.
• ³Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.
• ⁴Internal Medicine and Hepatology, Humanitas Clinical and Research Center IRCCS, Humanitas University, Milan, Italy.
• ⁵Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.
• ⁶Department of Experimental and Clinical Biochemical Sciences, University of Florence, Florence, Italy.
• ⁷Hepatology Unit, University Hospital of Pisa, Pisa, Italy.
• ⁸Gastroenterology Unit, Fondazione Casa Sollievo Della Sofferenza IRCCS, San Giovanni Rotondo, Italy.
• ⁹Division of Medicine and Hepatology, University Hospital of Messina "Policlinico G. Martino", Messina, Italy.
• ¹⁰Gastroenterology Unit, National Institute of Gastroenterology "S de Bellis" Research Hospital, Castellana Grotte, Italy.
• ¹¹Gastroenterology Unit, Department of Internal Medicine, University of Genova, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
• ¹²Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona, Italy.
• ¹³Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.
• ¹⁴Liver Unit, University Hospital of Cagliari, Cagliari, Italy.
• ¹⁵Clinic of Gastroenterology and Hepatology, Department of Medicine, Università degli Studi di Perugia, Perugia, Italy.
• ¹⁶DIMEC Università di Bologna, Policlinico di Sant'Orsola, Bologna, Italy.
• ¹⁷Liver Unit, San Camillo Hospital, Rome, Italy.
• ¹⁸Internal Medicine and Hepatology Unit, Policlinico Gemelli, Sapienza University, Rome, Italy.
• ¹⁹Medical Team Torino, Torino, Italy.
• ²⁰Liver Unit, Arnas Garibaldi, Catania, Italy.
• ²¹Department of Gastroenterology, University Hospital Sant'Anna, Ferrara, Italy.
• ²²IRCCS Sacro Cuore Institute Don Calabria, Gastroenterology, Negrar, Italy.
• ²³Hepatology Unit, San Giuseppe Hospital, Milan, Italy.
• ²⁴Department of Health Sciences, University "Magna Graecia" of Catanzaro, Italy.
• ²⁵Hepatology Unit, Santa Maria delle Grazie Hospital, Pozzuoli, Italy.
• ²⁶Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A.M. and A. Migliavacca" Center for Liver Disease, Milan, Italy.
• ²⁷Department of Infectious Diseases, Umberto I Hospital, Syracuse, Italy.
• ²⁸Department of Gastroenterology, Brotzu Hospital, Cagliari, Italy.
• ²⁹Gastroenterology and Hepatology Unit, University of Palermo, Palermo, Italy.
• ³⁰Internal Medicine Ospedale "R. Dimiccoli", Barletta, Italy.
• ³¹Hepatology Unit, Santo Spirito Hospital, Pescara, Italy.
• ³²Gastroenterology Unit, Ospedali Riuniti, Foggia, Italy.
• ³³Gastroenterology and Hepatology Unit, University Hospital Policlinico Vittorio Emanuele, Catania, Italy.
• ³⁴Department of Translational and Precision Medicine, University La Sapienza, Rome, Italy.
• ³⁵Liver and Gastroenterology Unit, Department of Health Sciences, Universita' degli Studi di Milano, Milan, Italy.
• ³⁶ASST Santi Paolo e Carlo, University Hospital San Paolo, Milan, Italy.
• ³⁷Department of Hepatology, Betania Hospital, Napoli, Italy.
• ³⁸Department of Infectious Diseases, D. Cotugno Hospital, Napoli, Italy.

Abstract

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.