Author information

¹University of Alberta, Edmonton, Alberta, Canada. Electronic address: montanol@ualberta.ca.

²University of Alberta, Edmonton, Alberta, Canada.

³Toronto Center for Liver Disease, UHN, Toronto, Canada.

⁴Dept of Epidemiology, Erasmus MC, Rotterdam, the Netherlands; IHPME, University of Toronto & Toronto Center for Liver Disease, UHN, Toronto, Canada.

⁵Geneva University Hospitals, Geneva, Switzerland.

⁶Unidad de Autoinmunidad Hepática, Sección de Hepatología y Trasplante Hepático, Hospital Italiano de Buenos Aires, Argentina.

⁷Division Liver and Biliopancreatic Disorders, Leuven, Belgium.

⁸University of Barcelona, Barcelona, Spain.

⁹Liver Unit, Hospital Clínic, Barcelona, Spain.

¹⁰University of São Paulo School of Medicine, San Paulo, Brazil.

¹¹University of Birmingham, Birmingham, United Kingdom.

¹²Division of Gastroenterology and Hepatology, Fondazione IRCCS Maggiore Hospital Policlinico Milan, Italy.

¹³University of Washington, Seattle, USA.

¹⁴Hospices civils de Lyon, Edouard Herriot Hospital Hepatogastroenterology Unit, and University of Lyon, Lyon, France.

¹⁵Newcastle University, Newcastle, United Kingdom.

¹⁶Dept of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, Netherlands.

¹⁷University of Texas Southwestern Medical Center, Dallas, USA.

¹⁸Hannover Medical School, Hannover, Germany.

¹⁹Dept. Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.

²⁰Niguarda transplant centre, Milan, Italy.

²¹University Hospital Inselspital, Bern, Switzerland.

²²University of Padova, Padova, Italy.

²³Tel Aviv Medical Centre, Tel Aviv, Israel.

²⁴University of Milano-Bicocca, Milan, Italy.

²⁵Gastroenterology Hepatology and Transplantation UNIT, ASST Papa Giovanni XXIII, Bergamo & Department of Medicine, University of Milano-Bicocca, Milan, Italy.

²⁶Massachusetts General Hospital, Harvard Medical School, Boston, USA.

²⁷Liver Center, Beth Israel Deaconess Medical Center, Department of Internal Medicine, Harvard Medical School, Boston, MA, USA.

²⁸Mount Sinai Medical Center, New York, USA.

²⁹University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

³⁰Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Germany.

³¹INSELSPITAL, Universitätsspital Bern, Switzerland.

³²Ghent University Hospital, Ghent, Belgium.

³³Epatocentro Ticino, Lugano, Switzerland.

³⁴University Hospital Virgen de la Victoria, Málaga, Spain.

³⁵Reference centre for inflammatory biliary diseases and auto-immune hepatitis, Saint-Antoine Hospital, Paris, France.

Abstract

Background & aims: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC.

Methods: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2-62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation.

Results: During a median follow-up of 8.7 years [IQR 4.3-12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p <0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p <0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p <0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival.

Conclusion: Patients with rPBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC.

Impact and implications: One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according to conventional prognostic scores, have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results supportsupport efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis.