Author information

¹Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, University Medical Center Rotterdam, The Netherlands.

²European Society for Organ Transplantation, Amsterdam, The Netherlands.

³European Liver Transplant Registry, Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation AP-HP Hôpital Paul Brousse, Université Paris-Saclay Villejuif, France.

⁴Department of Hepatology and Gastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

⁵Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, The Netherlands.

⁶Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris; Inserm UMR_S938, Saint-Antoine Research Center, Sorbonne University, Paris, France.

⁷Department of HPB Surgery, Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom.

⁸Institute of Liver Studies, King's College Hospital, London, United Kingdom.

⁹The Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.

¹⁰Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburg, United Kingdom.

¹¹Division of Transplantation, CLINTEC, Karolinska Institutet, Stockholm, Sweden.

¹²Department of Hepatology and Liver Transplantation, Royal Free Hospital, London, United Kingdom.

¹³Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge NIHR Biomedical Research Centre, Cambridge, United Kingdom.

Abstract

Background & aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC.

Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included.

Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9-17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p =0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p <0.001) or death (aHR 0.72, 95% CI 0.59-0.87, p <0.001), while these risks were higher with use of steroids (aHR 1.31, 95% CI 1.13-1.52, p <0.001, and aHR 1.34, 95% CI 1.15-1.56, p <0.001, respectively).

Conclusions: In this large LT registry, type of calcineurin inhibitor was not associated with long-term graft or recipient survival, providing reassurance regarding the use of Tac post LT in the population with PBC. Patients using MMF had a lower risk of graft loss and death, indicating that the threshold for combination treatment with Tac and MMF should be low.

Impact and implications: This study investigated the association between immunosuppressive drugs and the long-term survival of patients with primary biliary cholangitis (PBC) following donation after brain death liver transplantation. While tacrolimus has previously been related to a higher risk of PBC recurrence, the type of calcineurin inhibitor was not related to graft or patient survival among patients transplanted for PBC in the European Liver Transplant Registry. Additionally, maintenance use of mycophenolate was linked to lower risks of graft loss and death, while these risks were higher with maintenance use of steroids. Our findings should provide reassurance for physicians regarding the continued use of Tac after liver transplantation in the population with PBC, and suggest potential benefit from combination therapy with mycophenolate.