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Condon S, Levy C, Martin EF. Recurrent and De Novo Liver Disease After Liver Transplantation. Clin Liver Dis 2025; 29:313-335. [PMID: 40287274 DOI: 10.1016/j.cld.2024.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/29/2025]
Abstract
Disease recurrence after liver transplantation (LT) is common. Certain liver diseases such as autoimmune hepatitis and steatotic liver disease may appear de novo after LT. This review discusses post LT alcohol-associated liver disease, metabolic dysfunction-associated liver disease, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Both recurrent and de novo diseases are important causes of allograft failure.
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Affiliation(s)
- Sally Condon
- Transplant Hepatology/Gastroenterology, Swedish Organ Transplant Center, 1124 Columbia Street #600, Seattle, WA 98104, USA.
| | - Cynthia Levy
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1120 NW 14th Street, Miami, FL 33136, USA
| | - Eric F Martin
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1801 NW 9th Avenue, 7th Floor, Miami, FL 33136, USA
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2
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Vorasittha A, Sakamoto S, Yanagi Y, Degawa K, Kato H, Kodama T, Komine R, Yamada M, Uchida H, Fukuda A, Haga C, Yoshioka T, Kasahara M. Recurrence of Primary Sclerosing Cholangitis After Pediatric Liver Transplantation: A Single-Center, Retrospective Study in Japan. Pediatr Transplant 2025; 29:e70078. [PMID: 40217566 DOI: 10.1111/petr.70078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 03/23/2025] [Accepted: 03/31/2025] [Indexed: 04/14/2025]
Abstract
AIM Liver transplantation (LT) is a well-accepted treatment for primary sclerosing cholangitis (PSC) with generally good outcomes, although recurrent PSC (rPSC) poses significant challenges. This study aimed to describe patient characteristics and identify potential risk factors of rPSC in pediatric LT recipients. METHODS This retrospective study analyzed 13 pediatric patients who underwent LT for PSC at a single center. Patient characteristics, risk factors, and outcomes were compared between those with and without rPSC. RESULTS The median age at PSC diagnosis was 5.2 years and at LT, 15.4 years. Inflammatory bowel disease (IBD) was present in 12 patients (92.3%), and four (30.7%) had overlapping autoimmune hepatitis (AIH) before LT. Two patients received grafts from living-related donors, and 11 from deceased donors. During a median follow-up of 53 months, 4 of the 13 patients (30.7%) developed rPSC at a median of 48.9 months post-LT. Patients with rPSC tend to be younger at PSC diagnosis. All rPSC cases were associated with IBD, and half had AIH overlap, though the frequency difference was not significant. Acute cellular rejection (ACR) was universal in rPSC patients (100%) compared to nonrecurrent cases (33.3%, p = 0.07). One case of rPSC developed pulmonary hypertension following rPSC and succumbed to PH crisis, resulting in a 5-year patient survival rate of 82%. CONCLUSIONS The recurrence rate was high in pediatric patients with PSC. The observed association with immune-activating conditions raises the possibility of utilizing immunologic interventions to prevent rPSC, although further prospective studies are warranted to clarify the underlying mechanisms.
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Affiliation(s)
- Athaya Vorasittha
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Seisuke Sakamoto
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Yusuke Yanagi
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Kazuki Degawa
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Hirotaka Kato
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Tasuku Kodama
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Ryuji Komine
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Masaki Yamada
- Division for Advanced Medicine for Viral Infection, National Center for Child Health and Development, Tokyo, Japan
| | - Hajime Uchida
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Akinari Fukuda
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Chiduko Haga
- Department of Pathology, National Center for Child Health and Development, Tokyo, Japan
| | - Takako Yoshioka
- Department of Pathology, National Center for Child Health and Development, Tokyo, Japan
| | - Mureo Kasahara
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
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Montano-Loza AJ, Corpechot C, Burra P, Schramm C, Selzner N, Ronca V, Oo YH. Recurrence of autoimmune liver diseases after liver transplantation: Review and expert opinion statement. Liver Transpl 2025; 31:369-383. [PMID: 38857316 DOI: 10.1097/lvt.0000000000000419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 05/24/2024] [Indexed: 06/12/2024]
Abstract
Autoimmune liver diseases (AILDs) constitute the fourth most common indication for liver transplantation (LT) across the world. In general, the outcomes after LT are acceptable; however, disease recurrence after LT is common for all AILD, which can negatively affect graft and overall survival. Several questions persist, including the risk factors associated with recurrent disease, optimal antirejection medications, strategies to reduce the risk of recurrence, and how to best incorporate these strategies into clinical practice. For that reason, we assembled an international group of experts to review evidence to address these outstanding questions regarding LT for AILD. Survival rates after LT are ~90% and 70% at 1 and 5 years, and recurrent disease occurs in 10%-50% of patients with AILD. In patients with disease recurrence, graft survival decreased by 18% and 28% and overall survival by 8% and 12% at 5 and 10 years after LT, respectively. Recurrent autoimmune hepatitis is associated with high aminotransferases and immunoglobulin G (IgG) before LT, lymphoplasmacytic infiltrates in the explants, and may be associated with the absence of steroids after LT. However, the efficiency and safety of triple immunosuppressive maintenance therapy is still debatable. Younger age at diagnosis with primary biliary cholangitis or LT is associated with primary biliary cholangitis recurrence. Preventive use of ursodeoxycholic acid reduces the risk of recurrence and has a benefit in graft and patient survival. Episodes of systemic inflammation, including T-cell-mediated rejection, active ulcerative colitis, and episodes of cholangitis, are associated with recurrent PSC. Recurrent disease for AILD is associated with worse graft and patient survival. Patients with autoimmune hepatitis could be considered for long-term low-dose predniso(lo)ne, whereas patients with primary biliary cholangitis should be placed on preventive ursodeoxycholic acid after LT. There are no specific treatments for PSC recurrence; however, adequate control of inflammatory bowel disease and optimal immunosuppression to avoid T-cell-mediated rejection should be encouraged.
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Affiliation(s)
- Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Christophe Corpechot
- Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, European Reference Network for Hepatological Diseases (ERN RARE-LIVER), Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris; Inserm UMR_S938, Saint-Antoine Research Center, Sorbonne University, Paris, France
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology, European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University of Padova, Padova, Italy
| | - Christoph Schramm
- Martin Zeitz Center for Rare Diseases, and 1st Department of Medicine, European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Nazia Selzner
- Ajmera Transplant Center, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada
| | - Vincenzo Ronca
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Ye H Oo
- Center for Liver and Gastro Research & National Institute of Health Research Birmingham Biomedical Research Centre, University of Birmingham; Centre for Rare Disease and ERN Rare Liver Centre, Liver Transplant and Hepatobiliary Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
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4
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Mehtani R, Rathi S. Recurrence of Primary Disease After Adult Liver Transplant - Risk Factors, Early Diagnosis, Management, and Prevention. J Clin Exp Hepatol 2024; 14:101432. [PMID: 38975605 PMCID: PMC11222954 DOI: 10.1016/j.jceh.2024.101432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 04/14/2024] [Indexed: 07/09/2024] Open
Abstract
Liver transplantation offers a new lease of life to patients with end-stage liver disease and hepatocellular carcinoma. However, the implantation of an exogenous allograft and the accompanying immunosuppression bring their own challenges. Moreover, the persistence of risk factors for the initial liver insult place the new graft at a higher risk of damage. With the increasing number of liver transplants along with the improvement in survival posttransplant, the recurrence of primary disease in liver grafts has become more common. Pre-2015, the most common disease to recur after transplant was hepatitis C. However, directly acting antivirals have nearly eliminated this problem. The greatest challenge of disease recurrence we now face are those of nonalcoholic steatohepatitis, alcohol-related liver disease, and primary sclerosing cholangitis. We focus on the epidemiology and pathophysiology of the recurrence of primary disease after transplant. We also discuss means of early identification, risk stratification, prevention, and management of recurrent primary disease after liver transplantation.
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Affiliation(s)
- Rohit Mehtani
- Department of Hepatology, Amrita Institute of Medical Sciences and Research, Faridabad, Haryana, India
| | - Sahaj Rathi
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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5
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Mouchli MA, Osman MK, Busebee B, Taner T, Heimbach JK, Eaton J, Mousa O, Cole K, Watt KD. Long-term (15 y) complications and outcomes after liver transplantation for primary sclerosing cholangitis: Impact of donor and recipient factors. Liver Transpl 2024:01445473-990000000-00502. [PMID: 39451100 DOI: 10.1097/lvt.0000000000000523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 10/11/2024] [Indexed: 10/26/2024]
Abstract
With longer survival of patients with primary sclerosing cholangitis (PSC) undergoing liver transplantation (LT), the frequency and risk factors associated with vascular and biliary complications in the allograft and the impact on long-term outcomes are poorly understood. To assess frequency and risk factors for long-term outcomes in patients after LT for PSC. All recipients of LT for advanced stage PSC for a non-cholangiocarcinoma indication from 1984 to 2012, with follow-up through March 2022 (>10+ y follow-up), were identified. One-, 5-, and 10-year cumulative risks of complications were estimated using the Aalen-Johansen method, where death was considered a competing risk. Two hundred ninety-three patients (mean age, 47.3 ± 12 y) formed our study cohort. One hundred and thirty-four patients received LT before 1995, and 159 were transplanted after 1995. Over a median (IQR) follow-up of 15.0 (10.3-22.1) years, LT was complicated by hepatic artery thrombosis (N = 30), portal vein stenosis/thrombosis (N = 48), biliary leak (N = 47), biliary strictures (N = 87), recurrent PSC (N=107), and graft failure (N=70). The 1-, 5-, 10-, and 15-year cumulative incidence of recurrent PSC was 1.0%, 8.0%, 23.5%, and 34.3%, respectively. The type of donor and older donor age were associated with an increased risk of biliary strictures. Donor age >60 years was associated with an increased risk of recurrent PSC. Long-term patient and graft survival have not changed significantly for patients transplanted for PSC. Controlling transplant-related factors, such as donor age, prompt identification of vascular and biliary complications early, and long-term rigorous follow-up, is recommended to continue to improve on these outcomes.
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Affiliation(s)
- Mohamad A Mouchli
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fisher Titus Medical Center, Norwalk, Ohio, USA
| | - Mohamed K Osman
- Division of Gastroenterology, Department of Internal Medicine, Columbia University Irving Medical Center, New York, USA
| | - Bradley Busebee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Timucin Taner
- Department of Surgery, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | - Julie K Heimbach
- Department of Surgery, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | - John Eaton
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Department of Surgery, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | - Omar Mousa
- Department of Surgery, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic Health System, Mankato, Minnesota, USA
| | - Kristin Cole
- Division of Biomedical Statistics and Informatics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Department of Surgery, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
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Bittencourt PL, Nardelli MJ, Barros LL, Cançado GGL, Cançado ELR, Terrabuio DRB, Villela-Nogueira CA, Ferraz MLG, Codes L, Rotman V, Rocco R, Felga GE, Dotta DD, Martins ADS, Mendes LSC, da Silva MC, Hyppolito EB, Gomide GPM, Signorelli IV, de Oliveira MB, Ivantes CAP, Chindamo MC, de Almeida E Borges VF, Faria LC, Couto CA. Recurrence of Primary Sclerosing Cholangitis and De Novo Cholangiocarcinoma After Liver Transplantation: Results From the Brazilian Cholestasis Consortium. Clin Transplant 2024; 38:e70002. [PMID: 39436152 DOI: 10.1111/ctr.70002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 07/21/2024] [Accepted: 10/04/2024] [Indexed: 10/23/2024]
Abstract
BACKGROUND AND AIM Primary sclerosing cholangitis (PSC) has been shown to recur after liver transplantation (LT). Some studies have identified certain clinical and laboratory variables associated with an increased risk for recurrent PSC (rPSC) in Caucasians. Furthermore, de novo cholangiocarcinoma (CCA) has been reported anecdotally in patients with rPSC. This study aims to assess the prevalence of rPSC, identify its associated risk factors, and investigate the occurrence of de novo CCA in a highly admixed population from Brazil. METHODS All patients submitted to LT for PSC enrolled in the Brazilian Cholestasis Study Group database were retrospectively reviewed for the occurrence of rPSC and de novo CCA. RESULTS Ninety-six (58 males, mean age 32 ± 13 years) patients with PSC underwent LT. After 90 (39-154) months of follow-up (FU), rPSC was observed in 29 (30%) subjects. There were no significant associations between rPSC and age, gender, concurrent or de novo inflammatory bowel disease, MELD score at the time of LT or allograft rejection. The only factor associated with an increased risk of disease recurrence was time after LT. Although survival was decreased in patients who developed rPSC, this difference was not significant. Only one female patient developed de novo CCA after rPSC, 11 years after LT. CONCLUSIONS Recurrent PSC was observed in one-third of PSC LT patients in Brazil and was associated with longer time after LT. Despite its frequency, rPSC was not associated with a higher risk of graft loss or a significant reduction in posttransplant survival.
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Affiliation(s)
- Paulo Lisboa Bittencourt
- Hospital Português, Salvador, Brazil
- Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil
| | | | - Luísa Leite Barros
- Departamento de Gastroenterologia, Universidade de São Paulo, São Paulo, Brazil
| | - Guilherme Grossi Lopes Cançado
- Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Hospital da Polícia Militar de Minas Gerais, Belo Horizonte, Brazil
| | | | | | | | | | | | - Vivian Rotman
- Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Rodrigo Rocco
- Hospital Israelita Albert Einsten, São Paulo, Brazil
| | | | - Diogo Delgado Dotta
- Departamento de Gastroenterologia, Universidade de São Paulo, São Paulo, Brazil
| | | | | | | | | | | | | | | | | | - Maria Chiara Chindamo
- Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Hospital Barra D´or - Rede D´or São Luiz, Rio de Janeiro, Brazil
| | | | - Luciana Costa Faria
- Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Claudia Alves Couto
- Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Pan Z, Zhong L. Causal links between 13 autoimmune diseases and graft dysfunction: A Mendelian randomization study. Medicine (Baltimore) 2024; 103:e39666. [PMID: 39287258 PMCID: PMC11404874 DOI: 10.1097/md.0000000000039666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 08/17/2024] [Accepted: 08/22/2024] [Indexed: 09/19/2024] Open
Abstract
Previous studies have suggested a possible link between autoimmune diseases and graft dysfunction; however, a causal link remains unclear. Exposure factors were set as 13 autoimmune diseases, and outcomes were set as graft dysfunction. Mendelian randomization was used to analyze the causal link between exposure and outcome. Alopecia areata and asthma were linked to graft dysfunction (odds ratio 0.828; 95% confidence interval 0.699-0.980; P = .029; odds ratio 1.79; 95% confidence interval 1.069-2.996; P = .027). At the same time, primary sclerosing cholangitis was found to be heterogeneous as an exposure factor (P = .009), but no heterogeneity or pleiotropy was found in other exposure factors. Our preliminary findings show 2 autoimmune diseases as risk factors for graft dysfunction, 1 autoimmune disease as a protective factor for graft dysfunction and the mechanisms remain to be understood.
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Affiliation(s)
- Ziwen Pan
- Department of Organ Transplantation, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Lin Zhong
- Department of Organ Transplantation, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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8
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Taghavi SA, Safarpour AR, Ghahramani S, Moghadam SM, Shahramian I, Sivandzadeh GR, Nikeghbalian S, Tahani M, Saeian S, Malek-Hosseini SA. Study of Risk Factors Associated With Recurrent Primary Sclerosing Cholangitis After Liver Transplantation in Shiraz >From 2011 to 2021. EXP CLIN TRANSPLANT 2024; 22:531-539. [PMID: 39223811 DOI: 10.6002/ect.2024.0085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
OBJECTIVES Primary sclerosing cholangitis is an autoimmune illness affecting the intrahepatic and/or extrahepatic bile ducts that has a varying clinical history and no clear therapy. Recurrence of primary sclerosing cholangitis after transplantation can cause recurring liver failure, decreased survival, and the necessity for retransplant. Here, we explored the incidence of recurrence while also identifying the risk factors of primary sclerosing cholangitis. MATERIALS AND METHODS In this retrospective cohort study, we collected demographic and clinical data from patients with a history of primary sclerosing cholangitis after liver transplant between 2011 and 2021. With SPSS software, we compared results in 2 groups of patients (with and without recurrent sclerosing biliary cholangitis) in terms of demographic and clinical variables. RESULTS The study included 408 patients. Lower donor age and the occurrence of acute cellularrejection were shown to be key risk factors for recurrence of primary sclerosing cholangitis. Acute cellularrejection showed the best likelihood of predicting primary sclerosing cholangitis recurrence. As the number of acute cellular rejection episodes increased, so did the chance of primary sclerosing cholangitis. Death rate of patients with recurrence of primary sclerosing cholangitis was 40.8% (n = 20 patients) compared with 18.9% (n = 68 patients) in those without recurrence (significant at P < .001). CONCLUSIONS The recurrence of primary sclerosing cholangitis had a detrimental effect on survival after liver transplant. Modifiable risk variables have the potentialto affecttherapies on care and prevention of primary sclerosing cholangitis recurrence. Donor age and acute cellular rejection were risk factors for decreased survival and higher primary sclerosing cholangitis recurrence. The use of mycophenolate (Cellcept) increased recurrence, but tacrolimus reduced mortality.
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Affiliation(s)
- Seyed Alireza Taghavi
- >From the Gastroenterohepatology Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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9
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Nabulsi S, Otunla AA, Salciccioli J, Marshall DC, Villani V, Shanmugarajah K, Shalhoub J. HLA matching between donors and recipients improves clinical liver transplant graft survival. Liver Int 2024; 44:411-421. [PMID: 38010995 DOI: 10.1111/liv.15774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 10/03/2023] [Accepted: 10/16/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND AND AIMS The importance of human leukocyte antigen (HLA) matching between liver transplant donors and recipients on graft survival remains unclear and is not a clinical consideration in liver transplantation. This study aimed to determine the relationship between HLA matching and liver graft survival using a large-scale multi-centre database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication and donor status. METHODS This retrospective observational analysis was performed using 22 702 liver transplant recipients from the UNOS/OPTN database. Patients were divided into two groups based on number of HLA mismatches (0-3 mismatches vs. 4-6 mismatches) and then subcategorized by indication and donor status. Risk-adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan-Meier survival curves. RESULTS Allograft survival and risk of acute rejection were associated with degree of HLA mismatch. This association between HLA mismatch and graft survival persisted in individuals who underwent transplant for hepatitis, metabolic, drug toxicity, and congenital indications. Donor status also influenced the relationship between HLA mismatch and graft survival. Graft survival in DBD recipients was longer than in DCD in the 4-6 HLA mismatch group, whereas no significant difference was found in the 0-3 HLA mismatch group. CONCLUSION HLA mismatch significantly reduced graft survival and increased risk of acute rejection. This association was noted only in specific indications. These findings are of potential clinical relevance to organ allocation, allograft matching algorithms, immunosuppression protocols, and transplant surveillance.
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Affiliation(s)
- Sarah Nabulsi
- Department of Life Sciences, Imperial College London, London, UK
| | | | - Justin Salciccioli
- Department of Critical Care, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | | | - Vincenzo Villani
- Department of Transplantation, Memorial Hermann Health System, Houston, Texas, USA
| | | | - Joseph Shalhoub
- Academic Section of Vascular Surgery, Department of Surgery & Cancer, Imperial College London, London, UK
- Imperial Vascular Unit, Imperial College Healthcare NHS Trust, London, UK
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10
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Henson JB, King LY. Post-Transplant Management and Complications of Autoimmune Hepatitis, Primary Biliary Cholangitis, and Primary Sclerosing Cholangitis including Disease Recurrence. Clin Liver Dis 2024; 28:193-207. [PMID: 37945160 PMCID: PMC11033708 DOI: 10.1016/j.cld.2023.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Autoimmune liver diseases have unique post-transplant considerations. These recipients are at increased risk of rejection, and recurrent disease may also develop, which can progress to graft loss and increase mortality. Monitoring for and managing these complications is therefore important, though data on associated risk factors and immunosuppression strategies has in most cases been mixed. There are also other disease-specific complications that require management and may impact these decisions, including inflammatory bowel disease in PSC. Further work to better understand the optimal management strategies for these patients post-transplant is needed.
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Affiliation(s)
- Jacqueline B Henson
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, DUMC Box 3913, Durham, NC 27710, USA
| | - Lindsay Y King
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, DUMC Box 3923, Durham, NC 27710, USA.
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11
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van Munster KN, Bergquist A, Ponsioen CY. Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two? J Hepatol 2024; 80:155-168. [PMID: 37940453 DOI: 10.1016/j.jhep.2023.09.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 09/01/2023] [Accepted: 09/29/2023] [Indexed: 11/10/2023]
Abstract
Primary sclerosing cholangitis (PSC) was declared one of the biggest unmet needs in hepatology during International Liver Congress 2016 in Berlin. Since then, not much has changed unfortunately, largely due to the still elusive pathophysiology of the disease. One of the most striking features of PSC is its association with inflammatory bowel disease (IBD), with the majority of patients with PSC being diagnosed with extensive colitis. This review describes the epidemiology of IBD in PSC, its specific phenotype, complications and potential pathophysiological mechanisms connecting the two diseases. Whether PSC is merely an extra-intestinal manifestation of IBD or if PSC and IBD are two distinct diseases that happen to share a common susceptibility that leads to a dual phenotype is debated. Implications for the management of the two diseases together are also discussed. Overall, this review summarises the available data in PSC-IBD and discusses whether PSC and IBD are one or two disease(s).
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Affiliation(s)
- Kim N van Munster
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Annika Bergquist
- Department of Medicine Huddinge, Division of Hepatology, Karolinska Institutet, Department of Upper GI Disease, Karolinska University Hospital, Stockholm, Sweden
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, the Netherlands.
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12
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Aufhauser DD, Stalter L, Marka N, Leverson G, Al-Adra DP, Foley DP. Detrimental impact of early biopsy-proven rejection in liver transplantation. Clin Transplant 2024; 38:e15206. [PMID: 38041491 PMCID: PMC10843795 DOI: 10.1111/ctr.15206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 09/07/2023] [Accepted: 11/19/2023] [Indexed: 12/03/2023]
Abstract
Existing literature offers conflicting conclusions about whether early acute cellular rejection influences long-term outcomes in liver transplantation. We retrospectively collected donor and recipient data on all adult, first-time liver transplants performed at a single center between 2008 and 2020. We divided this population into two cohorts based on the presence of early biopsy-proven acute cellular rejection (EBPR) within the first 90 days post-transplant and compared outcomes between the groups. There were 896 liver transplants that met inclusion criteria with 112 cases (12.5%) of EBPR. Recipients who developed EBPR had higher biochemical Model for End-Stage Liver Disease scores (28 vs. 24, p < .01), but other donor and recipient characteristics were similar. Recipients with EBPR had similar overall survival compared to patients without EBPR (p = .09) but had decreased graft survival (p < .05). EBPR was also associated with decreased time to first episode of late (> 90 days post-transplant) rejection (p < .0001) and increased vulnerability to bacterial and viral infection (p < .05). In subgroup analysis of recipients with autoimmune indications for liver transplantation, EBPR had a more pronounced association with patient death (hazard ratio [HR] 3.9, p < .05) and graft loss (HR 4.0, p < .01). EBPR after liver transplant is associated with inferior graft survival, increased susceptibility to late rejections, and increased vulnerability to infection.
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Affiliation(s)
- David D Aufhauser
- Department of Surgery, University of Wisconsin, Madison, Wisconsin, USA
| | - Lily Stalter
- Department of Surgery, University of Wisconsin, Madison, Wisconsin, USA
| | - Nicholas Marka
- Clinical and Translational Science Institute, University of Minnesota, Minneapolis, Minnesota, USA
| | - Glen Leverson
- Department of Surgery, University of Wisconsin, Madison, Wisconsin, USA
| | - David P Al-Adra
- Department of Surgery, University of Wisconsin, Madison, Wisconsin, USA
| | - David P Foley
- Department of Surgery, University of Wisconsin, Madison, Wisconsin, USA
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13
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Berenguer M, de Martin E, Hessheimer AJ, Levitsky J, Maluf DG, Mas VR, Selzner N, Hernàndez-Èvole H, Lutu A, Wahid N, Zubair H. European Society for Organ Transplantation Consensus Statement on Biomarkers in Liver Transplantation. Transpl Int 2023; 36:11358. [PMID: 37711401 PMCID: PMC10498996 DOI: 10.3389/ti.2023.11358] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 07/25/2023] [Indexed: 09/16/2023]
Abstract
Currently, one-year survival following liver transplantation (LT) exceeds 90% in large international registries, and LT is considered definitive treatment for patients with end-stage liver disease and liver cancer. Recurrence of disease, including hepatocellular carcinoma (HCC), significantly hampers post-LT outcomes. An optimal approach to immunosuppression (IS), including safe weaning, may benefit patients by mitigating the effect on recurrent diseases, as well as reducing adverse events associated with over-/under-IS, including chronic kidney disease (CKD). Prediction of these outcome measures-disease recurrence, CKD, and immune status-has long been based on relatively inaccurate clinical models. To address the utility of new biomarkers in predicting these outcomes in the post-LT setting, the European Society of Organ Transplantation (ESOT) and International Liver Transplant Society (ILTS) convened a working group of experts to review literature pertaining to primary disease recurrence, development of CKD, and safe weaning of IS. Summaries of evidence were presented to the group of panelists and juries to develop guidelines, which were discussed and voted in-person at the Consensus Conference in Prague November 2022. The consensus findings and recommendations of the Liver Working Group on new biomarkers in LT, clinical applicability, and future needs are presented in this article.
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Affiliation(s)
- Marina Berenguer
- Hepatology and Liver Transplantation Unit, Hospital Universitario la Fe - IIS La Fe Valencia, CiberEHD and University of Valencia, Valencia, Spain
| | - Eleonora de Martin
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris-Saclay, Villejuif, France
| | - Amelia J. Hessheimer
- General & Digestive Surgery, Hospital Universitario La Paz, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Josh Levitsky
- Division of Gastroenterology and Hepatology, Department of Medicine, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Daniel G. Maluf
- Program in Transplantation, Department of Surgery, University of Maryland Medical Center, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Valeria R. Mas
- Surgical Sciences Research in Transplantation, Chief Surgical Sciences Division, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Nazia Selzner
- Ajmera Transplant Center, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | | | - Alina Lutu
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris-Saclay, Villejuif, France
| | - Nabeel Wahid
- Division of Gastroenterology and Hepatology, Department of Medicine, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Haseeb Zubair
- Surgical Sciences Division, University of Maryland School of Medicine, Baltimore, MD, United States
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14
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Assis DN, Bowlus CL. Recent Advances in the Management of Primary Sclerosing Cholangitis. Clin Gastroenterol Hepatol 2023; 21:2065-2075. [PMID: 37084929 DOI: 10.1016/j.cgh.2023.04.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 04/05/2023] [Accepted: 04/10/2023] [Indexed: 04/23/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by fibroinflammatory damage to the biliary tree, typically in the setting of inflammatory bowel disease, with an increased risk of liver failure and cholangiocarcinoma. A complex pathophysiology, heterogeneity in clinical features, and the rare nature of the disease have contributed to the lack of effective therapy to date. However, recent innovations in the characterization and prognostication of patients with PSC, in addition to new tools for medical management and emerging pharmacologic agents, give rise to the potential for meaningful progress in the next several years. This review summarizes current concepts in PSC and highlights particular areas in need of further study.
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15
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Kelly C, Zen Y, Heneghan MA. Post-Transplant Immunosuppression in Autoimmune Liver Disease. J Clin Exp Hepatol 2023; 13:350-359. [PMID: 36950491 PMCID: PMC10025678 DOI: 10.1016/j.jceh.2022.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 06/10/2022] [Accepted: 07/04/2022] [Indexed: 02/17/2023] Open
Abstract
Autoimmune liver diseases (AILDs) are a group of conditions where immune-mediated liver damage can lead to the need for transplantation. Collectively, they account for almost a quarter of all liver transplants. Outcomes in terms of graft and patient survival for all liver transplants have improved markedly over decades with improvements in patient selection, surgical techniques and longer-term care and this is also seen in patients with AILDs. The current five- and ten-year survival rates post-transplant in autoimmune disease are excellent, at 88% and 78%, respectively. A key factor in maintaining good outcomes post liver transplant for these autoimmune conditions is the immunosuppression strategy. These patients have increased the rates of rejection, and autoimmune conditions can all recur in the graft ranging from 12 to 60% depending on the population studied. Immunosuppressive regimens are centred on calcineurin inhibitors, often combined with low dose corticosteroids, with or without the addition of antimetabolite therapy. There is no clear evidence-based immunosuppressive regimen for these conditions, and a tailored approach balancing the individuals' immunological profile against the risks of immunosuppression is often used. There are disease-specific considerations to optimised graft function including the role of ursodeoxycholic acid in both primary biliary cholangitis and primary sclerosing cholangitis and the role and timing of colectomy in primary sclerosing cholangitis in inflammatory bowel disease patients. However, unmet needs still exist in the management of AILDs post liver transplantation particularly in building the evidence base for optimal immunosuppression as well as mitigating the risk of recurrent disease.
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Key Words
- AIH, Autoimmune hepatitis
- AILD, Autoimmune liver disease
- CNI, Calcineurin inhibitors
- IBD, Inflammatory bowel disease
- LT, Liver transplantation
- PBC, Primary biliary cholangitis
- PSC, Primary sclerosing cholangitis
- autoimmune liver disease
- immunosuppression
- rAIH, Recurrent autoimmune hepatitis
- rPBC, Recurrent primary biliary cholangitis
- rPSC, Recurrent primary sclerosing cholangitis
- transplantation
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Affiliation(s)
- Claire Kelly
- Institute of Liver Studies, Kings College Hospital, London, UK
| | - Yoh Zen
- Institute of Liver Studies, Kings College Hospital, London, UK
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16
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Bowlus CL, Arrivé L, Bergquist A, Deneau M, Forman L, Ilyas SI, Lunsford KE, Martinez M, Sapisochin G, Shroff R, Tabibian JH, Assis DN. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2023; 77:659-702. [PMID: 36083140 DOI: 10.1002/hep.32771] [Citation(s) in RCA: 125] [Impact Index Per Article: 62.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/26/2022] [Indexed: 01/28/2023]
Affiliation(s)
- Christopher L Bowlus
- Division of Gastroenterology , University of California Davis Health , Sacramento , California , USA
| | | | - Annika Bergquist
- Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden
| | - Mark Deneau
- University of Utah , Salt Lake City , Utah , USA
| | - Lisa Forman
- University of Colorado , Aurora , Colorado , USA
| | - Sumera I Ilyas
- Mayo Clinic College of Medicine and Science , Rochester , Minnesota , USA
| | - Keri E Lunsford
- Rutgers University-New Jersey Medical School , Newark , New Jersey , USA
| | - Mercedes Martinez
- Vagelos College of Physicians and Surgeons , Columbia University , New York , New York , USA
| | | | | | - James H Tabibian
- David Geffen School of Medicine at UCLA , Los Angeles , California , USA
| | - David N Assis
- Yale School of Medicine , New Haven , Connecticut , USA
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17
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Visseren T, Erler NS, Heimbach JK, Eaton JE, Selzner N, Gulamhusein A, van der Heide F, Porte RJ, van Hoek B, Alwayn IP, Metselaar HJ, IJzermans JN, Darwish Murad S. Inflammatory conditions play a role in recurrence of PSC after liver transplantation – an international multicentre study. JHEP Rep 2022; 4:100599. [PMID: 36426376 PMCID: PMC9678780 DOI: 10.1016/j.jhepr.2022.100599] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 09/19/2022] [Accepted: 09/21/2022] [Indexed: 12/03/2022] Open
Abstract
Background & Aims Liver transplantation (LT) for primary sclerosing cholangitis (PSC) is complicated by recurrence of PSC (rPSC) in up to 25% of recipients. Recurrence has been shown to be detrimental for both graft and patient survival. For both PSC and rPSC, a medical cure is not available. To predict and ideally to prevent rPSC, it is imperative to find risk factors for rPSC that can be potentially modified. Therefore, we aimed to identify such factors for rPSC in a large international multicentre study including 6 centres in PSC-prevalent countries. Methods In this international multicentre, retrospective cohort study, 531 patients who underwent transplantation for PSC were included. In 25% of cases (n = 131), rPSC was diagnosed after a median follow-up of 6.72 (3.29–10.11) years post-LT. Results In the multivariable competing risk model with time-dependent covariates, we found that factors representing an increased inflammatory state increase the risk for rPSC. Recurrent cholangitis before LT as indication for LT (hazard ratio [HR] 3.6, 95% CI 2.5–5.2), increased activity of inflammatory bowel disease after LT (HR 1.7, 95% CI 1.08–2.75), and multiple acute cellular rejections (HR: non-linear) were significantly and independently associated with an increased risk of rPSC. In contrast to the findings of previous studies, pretransplant colectomy was not found to be independently protective against the development of rPSC. Conclusions An increased inflammatory state before and after LT may play a causal and modifiable role in the development of rPSC. Pretransplant colectomy did not reduce the risk of rPSC per se. Recurrent cholangitis as indication for LT was associated with an increased risk of rPSC. Impact and implications Recurrence of PSC (rPSC) negatively affects survival after liver transplant (LT). Modifiable risk factors could guide clinical management and prevention of rPSC. We demonstrate that an increased inflammatory state both before and after LT increases the incidence of rPSC. As these are modifiable factors, they could serve as targets for future studies and therapies. We also added further evidence to the ongoing debate regarding preventive colectomy for rPSC by reporting that in our multicenter study, we could not find an independent association between colectomy and risk of rPSC.
rPSC occurred after LT in 25% of recipients in this multicentre study from 6 transplant centres (Europe and North America). An increased systemically inflammatory state, both before and after LT, increases the risk of rPSC development. Increased IBD activity post-LT was associated with a higher risk of rPSC development. Performing a colectomy before LT was not associated with a reduction of rPSC.
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18
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Martinez M, Perito ER, Valentino P, Mack CL, Aumar M, Broderick A, Draijer LG, Fagundes ED, Furuya KN, Gupta N, Horslen S, Jonas MM, Kamath BM, Kerkar N, Kim KM, Kolho KL, Koot BGP, Laborda TJ, Lee CK, Loomes KM, Miloh T, Mogul D, Mohammed S, Ovchinsky N, Rao G, Ricciuto A, Schwarz KB, Smolka V, Tanaka A, Tessier MEM, Venkat VL, Vitola BE, Woynarowski M, Zerofsky M, Deneau MR, Deneau MR. Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study. Hepatology 2021; 74:2047-2057. [PMID: 34008252 PMCID: PMC8530456 DOI: 10.1002/hep.31911] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 05/11/2021] [Accepted: 05/12/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIMS Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.
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Affiliation(s)
| | | | | | - Cara L Mack
- University of Colorado School of Medicine, Aurora, CO
| | | | - Annemarie Broderick
- Children’s Health Ireland at Crumlin & University College Dublin, Dublin, Ireland
| | | | | | - Katryn N. Furuya
- Mayo Clinic, Rochester, MN and Medical College of Wisconsin, Milwaukee, WI
| | - Nitika Gupta
- Emory University School of Medicine, Atlanta, GA
| | | | - Maureen M Jonas
- Boston Children’s Hospital and Harvard Medical School, Boston, MA
| | | | - Nanda Kerkar
- University of Rochester Medical Center, Rochester, NY
| | | | - Kaija-Leena Kolho
- University of Helsinki Hospital and Tampere University, Helsinki, Finland
| | - Bart GP Koot
- Amsterdam University Medical Center Amsterdam, The Netherlands
| | - Trevor J Laborda
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
| | | | | | | | | | | | - Nadia Ovchinsky
- Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
| | | | | | - Kathleen B Schwarz
- University of California San Diego, San Diego, CA and Johns Hopkins University, Baltimore, MD
| | | | | | | | | | | | - Marek Woynarowski
- Faculty of Medicine and Health Sciences, UJK Kielce, Poland (former IP CZD Warsaw)
| | | | - Mark R. Deneau
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
| | - Mark R. Deneau
- Department of Pediatrics University of Utah and Intermountain Primary Children’s Hospital Salt Lake City UT
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19
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Trivedi PJ, Hirschfield GM. Recent advances in clinical practice: epidemiology of autoimmune liver diseases. Gut 2021; 70:1989-2003. [PMID: 34266966 DOI: 10.1136/gutjnl-2020-322362] [Citation(s) in RCA: 127] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 06/24/2021] [Indexed: 12/13/2022]
Abstract
Autoimmune liver diseases are chronic inflammatory hepatobiliary disorders that when classically defined encompass three distinctive clinical presentations; primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Meaningful changes in disease epidemiology are reported, with increasing incidence and prevalence of AIH and PSC in Europe, and rising prevalence of PBC across Europe, North America and the Asia-Pacific region. However, there appears to be very significant global variation with contemporary incidence rates of disease per 100 000 ranging from 0.84 to 2.75 for PBC, 0.1 to 4.39 for PSC and 0.4 to 2.39 for AIH. Prevalence corresponds, and per 100 000 estimates for PBC range from 1.91 to 40.2, for PSC between 0.78 and 31.7 and for AIH from 4.8 to 42.9. Population-based studies and multicentre observational cohort series provide improved understanding of the clinical course that patients experience, highlighting variations in presenting phenotypes geographically and temporally. Collectively, while autoimmune liver diseases are rare, the clinical burden is disproportionately high relative to population incidence and prevalence. Age, sex and race also impact clinical outcomes, and patient morbidity and mortality are reflected by high need for gastroenterology, hepatology and organ transplant services.
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Affiliation(s)
- Palak J Trivedi
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre, University of Birmingham College of Medical and Dental Sciences, Birmingham, Birmingham, UK
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, UK
| | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Ontario, Canada
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20
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Berenguer M, Di Maira T, Baumann U, Mirza DF, Heneghan MA, Klempnauer JL, Bennet W, Ericzon BG, Line PD, Lodge PA, Zieniewicz K, Watson CJE, Metselaar HJ, Adam R, Karam V, Aguilera V. Characteristics, Trends, and Outcomes of Liver Transplantation for Primary Sclerosing Cholangitis in Female Versus Male Patients: An Analysis From the European Liver Transplant Registry. Transplantation 2021; 105:2255-2262. [PMID: 33196626 DOI: 10.1097/tp.0000000000003542] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The influence of sex on primary sclerosing cholangitis (PSC), pre- and postliver transplantation (LT) is unclear. Aims are to assess whether there have been changes in incidence, profile, and outcome in LT-PSC patients in Europe with specific emphasis on sex. METHODS Analysis of the European Liver Transplant Registry database (PSC patients registered before 2018), including baseline demographics, donor, biochemical, and clinical data at LT, immunosuppression, and outcome. RESULTS European Liver Transplant Registry analysis (n = 6463, 32% female individuals) demonstrated an increasing number by cohort (1980-1989, n = 159; 1990-1999, n = 1282; 2000-2009, n = 2316; 2010-2017, n = 2549) representing on average 4% of all transplant indications. This increase was more pronounced in women (from 1.8% in the first cohort to 4.3% in the last cohort). Graft survival rate at 1, 5, 10, 15, 20, and 30 y was 83.6%, 70.8%, 57.7%, 44.9%, 30.8%, and 11.6%, respectively. Variables independently associated with worse survival were male sex, donor and recipient age, cholangiocarcinoma at LT, nondonation after brain death donor, and reduced size of the graft. These findings were confirmed using a more recent LT population closer to the current standard of care (LT after the y 2000). CONCLUSIONS An increasing number of PSC patients, particularly women, are being transplanted in European countries with better graft outcomes in female recipients. Other variables impacting outcome include donor and recipient age, cholangiocarcinoma, nondonation after brain death donor, and reduced graft size.
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Affiliation(s)
- Marina Berenguer
- Hepatology and Liver Transplant Unit, La Fe University Hospital and Ciberehd, IISLaFe, Universidad de Valencia, Valencia, Spain
| | - Tommaso Di Maira
- Hepatology and Liver Transplant Unit, La Fe University Hospital and Ciberehd, IISLaFe, Valencia, Spain
| | - Ulrich Baumann
- Hannover Medical School, Paediatric Gastroenterology and Hepatology, Hannover, Germany
- University of Birmingham, Institute of Immunology and Immunotherapy, Birmingham, United Kingdom
| | - Darius F Mirza
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Queen Elizabeth University Hospitals Birmingham, NHS Foundation Trust, Birmingham, United Kingdom
| | - Michael A Heneghan
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
| | - Jurgen L Klempnauer
- Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - William Bennet
- Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Bo-Goran Ericzon
- Department of Transplantation Surgery, Karolinska University Hospital, Huddinge, Sweden
| | - Pål-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Peter A Lodge
- Hepatobiliary Surgery Unit, St James's University Hospital, Leeds, United Kingdom
| | - Krzysztof Zieniewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Christopher J E Watson
- Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Herold J Metselaar
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - René Adam
- Hepato-Biliary Center, AP-HP Paul Brousse Hospital, University of Paris-Sud, INSERM U935, Villejuif, France
| | - Vincent Karam
- ELTR, Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - Victoria Aguilera
- Hepatology and Liver Transplant Unit, La Fe University Hospital and Ciberehd, IISLaFe, Valencia, Spain
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21
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Tsien C, Selzner N. PSC recurrence post liver transplantation: retransplantation justified or not? Transpl Int 2021; 34:1754-1755. [PMID: 34411372 DOI: 10.1111/tri.14014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 08/05/2021] [Indexed: 11/29/2022]
Affiliation(s)
- Cynthia Tsien
- Ajmera Transplant Program, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Nazia Selzner
- Ajmera Transplant Program, Department of Medicine, University of Toronto, Toronto, ON, Canada
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22
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Leung KK, Deeb M, Fischer SE, Gulamhusein A. Recurrent Primary Sclerosing Cholangitis: Current Understanding, Management, and Future Directions. Semin Liver Dis 2021; 41:409-420. [PMID: 34182588 DOI: 10.1055/s-0041-1730950] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Patients with primary sclerosing cholangitis (PSC) constitute 5 to 15% of patients listed for liver transplantation worldwide. Although post-transplant outcomes are favorable, recurrent PSC (rPSC) occurs in an important subset of patients, with higher prevalence rates reported with increasing time from transplant. Given its association with poor graft outcomes and risk of retransplant, effort has been made to understand rPSC, its pathophysiology, and risk factors. This review covers these facets of rPSC and focuses on implicated risk factors including pretransplant recipient characteristics, inflammatory bowel-disease-related factors, and donor-specific and transplant-specific factors. Confirming a diagnosis of rPSC requires thoughtful consideration of alternative etiologies so as to ensure confidence in diagnosis, management, subsequent risk assessment, and counseling for patients. Unfortunately, no cure exists for rPSC; however, future large-scale efforts are underway to better characterize the natural history of rPSC and its associated risk factors with hopes of identifying potential key targets for novel therapies.
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Affiliation(s)
- Kristel K Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Maya Deeb
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Sandra E Fischer
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
| | - Aliya Gulamhusein
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
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23
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Visseren T, Erler NS, Polak WG, Adam R, Karam V, Vondran FWR, Ericzon BG, Thorburn D, IJzermans JNM, Paul A, van der Heide F, Taimr P, Nemec P, Pirenne J, Romagnoli R, Metselaar HJ, Darwish Murad S. Recurrence of primary sclerosing cholangitis after liver transplantation - analysing the European Liver Transplant Registry and beyond. Transpl Int 2021; 34:1455-1467. [PMID: 34028110 PMCID: PMC8456806 DOI: 10.1111/tri.13925] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 05/15/2021] [Accepted: 05/18/2021] [Indexed: 11/26/2022]
Abstract
Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post‐transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow‐up of 5.0 years (quantile 2.5%‐97.5%: 0.4–18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9–9.1) and patient survival (HR 2.3; 95% CI 1.5–3.3). Patients with rPSC underwent significantly more re‐transplants than those without rPSC (OR 3.6, 95% CI 2.7–4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant‐related covariates. Recurrence of PSC leads to higher number of re‐transplantations and a 33% decrease in 10‐year graft survival.
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Affiliation(s)
- Thijmen Visseren
- Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.,Department of Surgery, Division of Hepatopancreaticobiliary and Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Nicole Stephanie Erler
- Department of Biostatistics, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.,Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Wojciech Grzegorz Polak
- Department of Surgery, Division of Hepatopancreaticobiliary and Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - René Adam
- Centre Hépatobiliaire, AP-HP Hôpital Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Vincent Karam
- Centre Hépatobiliaire, AP-HP Hôpital Paul Brousse, Université Paris-Saclay, Villejuif, France
| | | | - Bo-Goran Ericzon
- Division of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre and UCL Institute of Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Jan Nicolaas Maria IJzermans
- Department of Surgery, Division of Hepatopancreaticobiliary and Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Andreas Paul
- Department of General and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Frans van der Heide
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Centre Groningen, Groningen, The Netherlands
| | - Pavel Taimr
- Department of Hepatogastroenterology, Institut Klinické Experimentální Medicíny, Prague, Czech Republic
| | - Petr Nemec
- Centre of Cardiovascular Surgery and Transplantations, Brno, Czech Republic
| | - Jacques Pirenne
- Abdominal Transplantation Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Renato Romagnoli
- Liver Transplantation Center, Azienda Ospedaliero-Universitaria, Città della Salute e della Scienza di Torino, Turin, Italy
| | - Herold Johnny Metselaar
- Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Sarwa Darwish Murad
- Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
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24
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Abstract
Autoimmune liver diseases are characterized by immune-mediated inflammation and eventual destruction of the hepatocytes and the biliary epithelial cells. They can progress to irreversible liver damage requiring liver transplantation. The post-liver transplant goals of treatment include improving the recipient’s survival, preventing liver graft-failure, and decreasing the recurrence of the disease. The keystone in post-liver transplant management for autoimmune liver diseases relies on identifying which would be the most appropriate immunosuppressive maintenance therapy. The combination of a steroid and a calcineurin inhibitor is the current immunosuppressive regimen of choice for autoimmune hepatitis. A gradual withdrawal of glucocorticoids is also recommended. On the other hand, ursodeoxycholic acid should be initiated soon after liver transplant to prevent recurrence and improve graft and patient survival in primary biliary cholangitis recipients. Unlike the previously mentioned autoimmune diseases, there are not immunosuppressive or disease-modifying agents available for patients with primary sclerosing cholangitis. However, colectomy and annual colonoscopy are key components during the post-liver transplant period.
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25
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Akamatsu N, Hasegawa K, Egawa H, Ohdan H, Yoshizawa A, Kokudo N, Tazuma S, Tanaka A, Takikawa H. Donor age (≥45 years) and reduced immunosuppression are associated with the recurrent primary sclerosing cholangitis after liver transplantation - a multicenter retrospective study. Transpl Int 2021; 34:916-929. [PMID: 33629379 DOI: 10.1111/tri.13852] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 01/18/2021] [Accepted: 02/22/2021] [Indexed: 01/25/2023]
Abstract
The present study investigated the possible risk factors, including relationship/HLA matching between donor and recipient, and immunosuppressive therapies on the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LT). Subjects were 197 recipients of LT for PSC, among whom 180 surviving more than 1 year after LT were further analyzed for risk factors of recurrence. The 5- and 10-year patient- and graft survival rates were 83% and 68%, and 71% and 62%, respectively. The overall PSC recurrence rate was 25% with a 5- and 10-year graft survival rate of 34% and 18%, which was significantly lower than the survival rate of those without recurrence (P < 0.001). Univariate analysis identified the following as risk factors for recurrence: donor age (P < 0.001), cyclosporine use (P = 0.012), mono or no immunosuppressive agent (P < 0.001), postoperative biliary complication (P < 0.001), and active intestinal bowel disease after LT (P < 0.001). Among these factors, donor age ≥45 years [hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.21-2.69; P = 0.003] and mono or no immunosuppressive agent 1-year after LT (HR, 2.38; 95% CI, 1.23-3.45; P = 0.011) were identified as independent risk factors in the final multivariate Cox regression model. The results were similar in sub-analysis for ABO-identical/compatible adult living donor LT cases.
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Affiliation(s)
- Nobuhisa Akamatsu
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroto Egawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Atsushi Yoshizawa
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Susumu Tazuma
- Department of General Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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26
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Shroff H, Lemmer A, Maddur H. PRO: Patients With Alcoholic Hepatitis Should Be Considered for Liver Transplantation. Clin Liver Dis (Hoboken) 2020; 16:178-181. [PMID: 33318783 PMCID: PMC7727854 DOI: 10.1002/cld.942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 01/25/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Hersh Shroff
- Division of Gastroenterology and HepatologyDepartment of MedicineNorthwestern UniversityChicagoIL
| | - Alexander Lemmer
- Division of Gastroenterology and HepatologyDepartment of MedicineNorthwestern UniversityChicagoIL
| | - Haripriya Maddur
- Division of Gastroenterology and HepatologyDepartment of MedicineNorthwestern UniversityChicagoIL
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27
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Ip S, Bhanji RA, Ebadi M, Mason AL, Montano-Loza AJ. De novo and recurrent liver disease. Best Pract Res Clin Gastroenterol 2020; 46-47:101688. [PMID: 33158472 DOI: 10.1016/j.bpg.2020.101688] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/03/2020] [Accepted: 09/18/2020] [Indexed: 01/31/2023]
Abstract
Decompensated cirrhosis due to nonalcoholic steatohepatitis (NASH), and autoimmune liver diseases (AILD) are the most common indications for liver transplantation (LT). AILD include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). NASH and AILD share some peculiarities as they can recur in the new graft, compromising the quality of life, and graft and patient survival. De novo NASH or AIH connotes the development of these liver diseases in patients transplanted for other indications. The diagnosis of recurrent or de novo liver disease usually requires a liver biopsy aside from recurrent PSC, which can be diagnosed with compatible imaging studies and exclusion of other causes of biliary strictures. The treatment of recurrent NASH is lifestyle modifications aiming for weight loss. Recurrent and de novo AIH is usually treated with corticosteroids with or without azathioprine. Recurrent PBC should be treated with ursodeoxycholic acid. There are no proven treatment options for recurrent PSC. Patients with graft failure should be considered for repeat LT. Future investigations should use standardized diagnostic criteria for each disease, seek diagnostic biomarkers, and evaluate treatments that improve outcomes.
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Affiliation(s)
- Stephen Ip
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Rahima A Bhanji
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Maryam Ebadi
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Andrew L Mason
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Aldo J Montano-Loza
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
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28
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Dekkers N, Westerouen van Meeteren M, Wolterbeek R, Farina Sarasqueta A, Laleman W, Inderson A, Desschans B, van Hoek B, Sebib Korkmaz K, Vermeire S, Maljaars J. Does mucosal inflammation drive recurrence of primary sclerosing cholangitis in liver transplantion recipients with ulcerative colitis? Dig Liver Dis 2020; 52:528-533. [PMID: 32147286 DOI: 10.1016/j.dld.2020.02.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 01/20/2020] [Accepted: 02/05/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Liver transplantation remains the only effective evidence based treatment for advanced primary sclerosing cholangitis. However, recurrence of disease occurs in approximately 18%. AIMS This study aimed to assess risk factors of recurrence of primary sclerosing cholangitis. METHODS A retrospective cohort study was performed on patients undergoing transplantation for recurrence of primary sclerosing cholangitis in two academic centers (Leuven, Belgium and Leiden, The Netherlands). Besides other risk factors, the degree of mucosal inflammation was assessed as a potential risk factor using histological Geboes scores. RESULTS 81 patients were included, of which 62 (76.5%) were diagnosed with ulcerative colitis. Seventeen patients (21.0%) developed rPSC during a median follow-up time of 5.2 years. In a subset of 42 patients no association was found between the degree of mucosal inflammation and recurrence, using both original Geboes scores and multiple cut-off points. In the total cohort, cytomegaloviremia post-transplantation (HR: 4.576, 95%CI 1.688-12.403) and younger receiver age at time of liver transplantation (HR: 0.934, 95%CI 0.881-0.990) were independently associated with an increased risk of recurrence of disease. CONCLUSION This study found no association between the degree of mucosal inflammation and recurrence of primary sclerosing cholangitis. An association with recurrence was found for cytomegaloviremia post-liver transplantation and younger age at time of liver transplantation.
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Affiliation(s)
- Nik Dekkers
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands.
| | - Menso Westerouen van Meeteren
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands
| | - Ron Wolterbeek
- Leiden University Medical Centre, Department of Medical Statistics, LUMC, Leiden, The Netherlands
| | - Arantza Farina Sarasqueta
- Leiden University Medical Centre, Department of Pathology, LUMC, Leiden, The Netherlands; Amsterdam University Medical Centre, Department of Pathology, AUMC, Amsterdam, The Netherlands
| | - Wim Laleman
- University Hospitals Leuven, Department of Gastroenterology-Hepatology, Division of Liver and Biliopancreatic Disorders, KU Leuven, Leuven, Belgium; KU Leuven, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), Leuven, Belgium; University Hospitals Leuven, Department of Abdominal Transplant Surgery & Transplant Coordination, KU Leuven, Belgium
| | - Akin Inderson
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands
| | - Bruno Desschans
- University Hospitals Leuven, Department of Gastroenterology-Hepatology, Division of Liver and Biliopancreatic Disorders, KU Leuven, Leuven, Belgium
| | - Bart van Hoek
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands
| | - Kerem Sebib Korkmaz
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands
| | - Severine Vermeire
- KU Leuven, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology-Hepatology, KU Leuven, Belgium
| | - Jeroen Maljaars
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands
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29
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Tanaka A, Kono H, Leung PSC, Gershwin ME. Recurrence of disease following organ transplantation in autoimmune liver disease and systemic lupus erythematosus. Cell Immunol 2019; 347:104021. [PMID: 31767117 DOI: 10.1016/j.cellimm.2019.104021] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 11/01/2019] [Accepted: 11/15/2019] [Indexed: 12/15/2022]
Abstract
Disease recurrence after organ transplantation associated with graft failure is a major clinical challenge in autoimmune diseases. Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune Hepatitis (AIH) are the three most common (autoimmune liver diseases) ALD for which liver transplantation (LT) is the most effective treatment option for patients with end-stage diseases. Although the 5- and 10-year survival rates of post-LT patients are remarkable (80-84% and 71-79% in PBC, 73-87% and 58-83% in PSC, 76-79% and 67-77% respectively in AIH patients), post-LT disease recurrence is not uncommon. Here, we summarize literature findings on disease recurrence of these ALD with emphasis on the incidence, risk factors and impact on long-term outcome. We noted that the incidence of disease recurrence varies between studies, which ranges from 53% to 10.9% in PBC, 8.2% to 44.7% in PSC and 7% to 42% in AIH. The variations are likely due to differences in study design, such as sample size, duration of studies and follow up time. This is further compounded by the lack of precise clinical diagnosis criteria and biomarkers of disease recurrence in these ALD, variation in post-LT treatment protocols to prevent disease recurrence and a multitude of risk factors associated with these ALD. While recurrence of PBC and AIH does not significantly impact long term outcome including overall survival, recurrent PSC patients often require another LT. Renal transplantation, like LT, is the treatment of choice in patients with end-stage lupus nephritis. While calcineurin inhibitor (CNI) and immunosuppressive drugs have improved the survival rate, post-transplant recurrence of lupus nephritis from surveillance-biopsy proven lupus nephritis range from 30% to 44%. On the other hand, recurrence of post-transplant lupus nephritis from registry survey analysis were only 1.1% to 2.4%. In general, risk factors associated with an increased frequency of post-transplant recurrence of autoimmune diseases are not clearly defined. Large scale multi-center studies are needed to further define guidelines for the diagnosis and clinical management to minimize disease recurrence and improve outcomes of post-transplant patients.
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Affiliation(s)
- Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Hajime Kono
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Patrick S C Leung
- Division of Rheumatology Allergy and Clinical Immunology, University of California School of Medicine, Davis, CA, United States
| | - M Eric Gershwin
- Division of Rheumatology Allergy and Clinical Immunology, University of California School of Medicine, Davis, CA, United States.
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30
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Steenstraten IC, Sebib Korkmaz K, Trivedi PJ, Inderson A, van Hoek B, Rodriguez Girondo MDM, Maljaars PWJ. Systematic review with meta-analysis: risk factors for recurrent primary sclerosing cholangitis after liver transplantation. Aliment Pharmacol Ther 2019; 49:636-643. [PMID: 30740723 PMCID: PMC6593422 DOI: 10.1111/apt.15148] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 08/20/2019] [Accepted: 12/29/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND After liver transplantation primary sclerosing cholangitis (PSC), the condition returns in the transplanted liver in a subset of patients (recurrent primary sclerosing cholangitis, rPSC). AIM To define risk factors for rPSC. METHODS We searched Pubmed, Embase, Web of Science, and Cochrane library for articles published until March 2018. Studies addressing risk factors for developing rPSC were eligible for inclusion. A random effects meta-analysis was conducted using hazard ratios (HR) as effect measure. Study quality was evaluated with the Newcastle Ottawa scale. Statistical analysis was performed using Cochrane Review Manager. RESULTS The electronic database search yielded 449 results. Twenty-one retrospective cohort studies met the inclusion criteria for the review; 14 were included in the meta-analysis. The final cohort included 2159 patients (age range 31-49 years, 68.8% male), of whom 17.7% developed rPSC. Colectomy before liver transplantation, HR 0.65 (95% CI: 0.42-0.99), cholangiocarcinoma before liver transplantation, HR 2.42 (95% CI: 1.20-4.86), inflammatory bowel disease, HR 1.73 (95% CI: 1.17-2.54), donor age, HR 1.24 (95% CI 1.0-1.45) per ten years, MELD score, HR 1.05 (95% CI: 1.02-1.08) per point and acute cellular rejection, HR of 1.94 (95% CI: 1.32-2.83) were associated with the risk of rPSC. CONCLUSIONS Multiple risk factors for rPSC were identified. Colectomy before liver transplantation reduced the risk of rPSC.
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Affiliation(s)
- Iris C. Steenstraten
- Department of Gastroenterology and HepatologyLeiden University Medical CentreLeidenThe Netherlands
| | - Kerem Sebib Korkmaz
- Department of Gastroenterology and HepatologyLeiden University Medical CentreLeidenThe Netherlands
| | - Palak J. Trivedi
- National Institute for Health Research (NIHR) Birmingham Biomedical Research CentreBirminghamUK,University Hospitals BirminghamBirminghamUK,Institute of Immunology and ImmunotherapyUniversity of BirminghamBirminghamUK,Institute of Applied Health ResearchUniversity of BirminghamUK
| | - Akin Inderson
- Department of Gastroenterology and HepatologyLeiden University Medical CentreLeidenThe Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and HepatologyLeiden University Medical CentreLeidenThe Netherlands
| | | | - P. W. Jeroen Maljaars
- Department of Gastroenterology and HepatologyLeiden University Medical CentreLeidenThe Netherlands
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31
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Bajer L, Slavcev A, Macinga P, Sticova E, Brezina J, Roder M, Janousek R, Trunecka P, Spicak J, Drastich P. Risk of recurrence of primary sclerosing cholangitis after liver transplantation is associated with de novo inflammatory bowel disease. World J Gastroenterol 2018; 24:4939-4949. [PMID: 30487703 PMCID: PMC6250922 DOI: 10.3748/wjg.v24.i43.4939] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 10/20/2018] [Accepted: 11/13/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate risk factors for primary sclerosing cholangitis (PSC) recurrence (rPSC) after orthotopic liver transplantation (OLT) in patients with well-preserved colons.
METHODS We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with follow-up of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen (HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical methods.
RESULTS Altogether, 31 men and 16 women with a median (range) age of 36 (15-68) years at the time of OLT and a median follow-up of 122 (60-249) mo were included. rPSC was confirmed in 21/47 (44.7%) of patients, a median 63 (12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio (HR): 4.02, 95% confidence interval (CI): 1.58-10.98] and history of acute cellular rejection (rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis (rPSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor (rPSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04 (rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03 (rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07 (rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective roles.
CONCLUSION De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation.
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Affiliation(s)
- Lukas Bajer
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
| | - Antonij Slavcev
- Department of Immunogenetics, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
| | - Peter Macinga
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
| | - Eva Sticova
- Department of Clinical and Transplant Pathology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
| | - Jan Brezina
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
| | - Matej Roder
- Department of Immunogenetics, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
| | - Radim Janousek
- Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
| | - Pavel Trunecka
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
| | - Julius Spicak
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
| | - Pavel Drastich
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
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32
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Patel YA, Henson JB, Wilder JM, Zheng J, Chow SC, Berg CL, Knechtle SJ, Muir AJ. The impact of human leukocyte antigen donor and recipient serotyping and matching on liver transplant graft failure in primary sclerosing cholangitis, autoimmune hepatitis, and primary biliary cholangitis. Clin Transplant 2018; 32:e13388. [PMID: 30136315 DOI: 10.1111/ctr.13388] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 07/11/2018] [Accepted: 08/16/2018] [Indexed: 12/19/2022]
Abstract
Human leukocyte antigen (HLA) serotyping is not considered to have significant impact on liver graft survival and does not factor into U.S. organ allocation. Immune-related liver diseases such as primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and primary biliary cholangitis (PBC) have been speculated to represent a disease subgroup that may have significantly different graft outcomes depending on HLA donor/recipient characterization. The aim of this study was to investigate whether HLA serotyping/matching influenced post-transplant graft failure for immune-related liver diseases using the United Network for Organ Sharing database. From 1994 to 2015, 5665 patients underwent first-time liver-only transplants for PSC, AIH, and PBC with complete graft survival and donor/recipient HLA data. Graft failure was noted in 38.6% (2188/5665), and all groups had comparable 5-year graft survival (75.1%-78.8%, P = 0.069). The overall degree of, and loci-specific mismatch level, did not influence outcomes. Multivariable Cox proportional hazards regression noted increased graft failure risk for recipient HLA-B7, HLA-B57, HLA-B75, HLA-DR13 and donor HLA-B55, HLA-B58, and HLA-DR8 for PSC patients, protective effects for recipient HLA-DR1 and HLA-DR3 for AIH patients, and increased risk for HLA-DR7 for AIH patients. These findings warrant further investigation to evaluate the impact of HLA serotyping on post-transplant outcomes.
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Affiliation(s)
- Yuval A Patel
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina
| | | | - Julius M Wilder
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.,Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
| | - Jiayin Zheng
- Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina
| | - Schein-Chung Chow
- Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina
| | - Carl L Berg
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina
| | - Stuart J Knechtle
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, North Carolina
| | - Andrew J Muir
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.,Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
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33
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Abstract
PURPOSE OF REVIEW Review the current knowledge about recurrent primary sclerosing cholangitis (rPSC) after transplant in children. RECENT FINDINGS Recurrent PSC is a significant complication that afflicts 16% of children after liver transplantation for primary sclerosing cholangitis (PSC) at a median onset of 38 months post-transplant. Possible risk factors include younger age at PSC diagnosis or transplant, the presence of overlap syndrome or IBD, and post-transplant induction with thymoglobulin. rPSC impairs the patient's quality of life and can be detrimental to the graft. Preventive options and therapeutic measures are limited. Ursodeoxycholic acid is widely used, but its effect on long-term outcome is unknown. Vancomycin can improve the biochemical profile of rPSC, but it remains unknown whether it halts the disease progression. Pediatric liver transplant for primary sclerosis cholangitis can be complicated by recurrence of the disease, which portends poor outcomes. Although few risk factors have been implicated, larger studies with longer follow-ups are needed to characterize cardinal risk factors for rPSC, as well as evaluate possible preventative and therapeutic options.
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Affiliation(s)
- Nisreen Soufi
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Southern California, Los Angeles, CA, USA
| | - Fateh Bazerbachi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Mark Deneau
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Utah, Salt Lake City, UT, 84113, USA.
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Sedki M, Levy C. Update in the Care and Management of Patients with Primary Sclerosing Cholangitis. Curr Gastroenterol Rep 2018; 20:29. [PMID: 29886518 DOI: 10.1007/s11894-018-0635-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
PURPOSE OF REVIEW Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease for which specific medical therapy is not available. The goals of treatment are primarily early detection and management of complications. In this review, we discuss novel therapies under evaluation and provide the foundation for surveillance strategies. RECENT FINDINGS Drugs under investigation include norursodeoxycholic acid, nuclear receptor agonists, anti-fibrotics, antibiotics, and anti-inflammatory drugs. Endoscopic therapy is indicated for symptomatic dominant strictures and in the work-up of malignancies. Recently, the use of stents was associated with an increased rate of complications compared to balloon dilatation; and long-term stenting should be avoided. Malignancies currently account for most of the PSC-related mortality. Many drugs are emerging for the treatment of PSC but liver transplantation is the only treatment modality shown to prolong survival. PSC recurrence occurs in up to 35% of transplanted allografts within a median of 5 years. Surveillance for hepatobiliary and colorectal malignancies is indicated.
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Affiliation(s)
- Mai Sedki
- Department of Internal Medicine, University of Miami/Jackson Memorial Hospital, Miami, FL, USA
| | - Cynthia Levy
- Division of Hepatology, University of Miami Miller School of Medicine, 1500 NW 12th Avenue, Suite 1101, Miami, FL, USA.
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35
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Tabibian JH, Bowlus CL. WITHDRAWN: Primary sclerosing cholangitis: A review and update. LIVER RESEARCH 2018. [DOI: 10.1016/j.livres.2017.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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36
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Lindström L, Jørgensen KK, Boberg KM, Castedal M, Rasmussen A, Rostved AA, Isoniemi H, Bottai M, Bergquist A. Risk factors and prognosis for recurrent primary sclerosing cholangitis after liver transplantation: a Nordic Multicentre Study. Scand J Gastroenterol 2018; 53:297-304. [PMID: 29301479 DOI: 10.1080/00365521.2017.1421705] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The risk for recurrent primary sclerosing cholangitis (rPSC) after liver transplantation is associated with inflammatory bowel disease (IBD). We assessed the frequency of rPSC and studied risk factors for recurrent disease with special focus on IBD. We also evaluated the importance of rPSC for prognosis. MATERIALS AND METHODS All liver transplanted PSC patients in the Nordic countries between 1984 and 2007 (n = 440), identified by the Nordic Liver Transplant Registry, were studied. Data were retrieved from patients' chart reviews. Multivariable Cox regression models were used to calculate risk factors for rPSC and death. RESULTS Of the 440 patients with a follow-up time after liver transplantation of 3743 patient years, rPSC was diagnosed in 19% (n = 85). Colectomy before liver transplantation was associated with a reduced risk of rPSC (HR 0.49; 95% CI, 0.26-0.94, p = 0.033). Neither high IBD activity nor presence of IBD flares before or after liver transplantation was associated with rPSC. Treatment with tacrolimus was an independent risk factor associated with increased risk for rPSC (HR, 1.81; 95% CI, 1.15-2.86, p = 0.010). The risk of dying or needing a re-transplantation after rPSC was increased in all age groups, but highest in patients transplanted before 40 years of age (HR 7.3; 95% CI, 4.1-12.8, p = 0.0001). CONCLUSIONS This study confirms that colectomy before liver transplantation is associated with a decreased risk of rPSC. Inflammatory activity of IBD was not associated with the risk of rPSC. Tacrolimus was an independent risk factor for PSC recurrence and its use as first line immunosuppression in PSC needs further study.
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Affiliation(s)
- Lina Lindström
- a Centre for Digestive Diseases, Division of Hepatology , Karolinska University Hospital, Karolinska Institutet , Stockholm , Sweden
| | - Kristin K Jørgensen
- b Department of Transplantation Medicine, Section for Gastroenterology and Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation , Oslo University Hospital Rikshospitalet , Oslo , Norway.,c Department of Gastroenterology , Akershus University Hospital , Lørenskog , Norway
| | - Kirsten M Boberg
- b Department of Transplantation Medicine, Section for Gastroenterology and Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation , Oslo University Hospital Rikshospitalet , Oslo , Norway.,d Institute of Clinical Medicine , University of Oslo , Oslo , Norway
| | - Maria Castedal
- e Transplant Institute , Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Allan Rasmussen
- f Department of Surgery and Liver Transplantation , Rigshospitalet , Copenhagen , Denmark
| | | | - Helena Isoniemi
- g Department of Surgery , University of Helsinki and Helsinki University Hospital , Helsinki , Finland
| | - Matteo Bottai
- h Unit of Biostatistics, Institute of Environmental Medicine , Karolinska Institutet , Stockholm , Sweden
| | - Annika Bergquist
- a Centre for Digestive Diseases, Division of Hepatology , Karolinska University Hospital, Karolinska Institutet , Stockholm , Sweden
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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38
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Goet JC, Hansen BE, Tieleman M, van Hoek B, van den Berg AP, Polak WG, Dubbeld J, Porte RJ, Konijn-Janssen C, de Man RA, Metselaar HJ, de Vries AC. Current policy for allocation of donor livers in the Netherlands advantages primary sclerosing cholangitis patients on the liver transplantation waiting list-a retrospective study. Transpl Int 2017; 31:590-599. [DOI: 10.1111/tri.13097] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 09/18/2017] [Accepted: 11/12/2017] [Indexed: 12/14/2022]
Affiliation(s)
- Jorn C. Goet
- Department of Gastroenterology and Hepatology; Erasmus University Medical Center; Rotterdam The Netherlands
| | - Bettina E. Hansen
- Department of Gastroenterology and Hepatology; Erasmus University Medical Center; Rotterdam The Netherlands
- Toronto Center for Liver Disease; Toronto General Hospital; University of Toronto; Toronto Canada
- Institute of Health Policy, Management and Evaluation; University of Toronto; Toronto Canada
| | - Madelon Tieleman
- Department of Gastroenterology and Hepatology; Erasmus University Medical Center; Rotterdam The Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology; Leiden University Medical Center; Leiden The Netherlands
| | - Aad P. van den Berg
- Department of Gastroenterology and Hepatology; University Medical Center Groningen; Groningen The Netherlands
| | - Wojciech G. Polak
- Department of Surgery; Erasmus University Medical Center; Rotterdam The Netherlands
| | - Jeroen Dubbeld
- Department of Surgery; Leiden University Medical Center; Leiden The Netherlands
| | - Robert J. Porte
- Department of Surgery; University Medical Center Groningen; Groningen The Netherlands
| | | | - Robert A. de Man
- Department of Gastroenterology and Hepatology; Erasmus University Medical Center; Rotterdam The Netherlands
| | - Herold J. Metselaar
- Department of Gastroenterology and Hepatology; Erasmus University Medical Center; Rotterdam The Netherlands
| | - Annemarie C. de Vries
- Department of Gastroenterology and Hepatology; Erasmus University Medical Center; Rotterdam The Netherlands
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39
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Tabibian JH, Bowlus CL. Primary sclerosing cholangitis: A review and update. LIVER RESEARCH (BEIJING, CHINA) 2017; 1:221-230. [PMID: 29977644 PMCID: PMC6028044 DOI: 10.1016/j.livres.2017.12.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease of uncertain etiology characterized biochemically by cholestasis and histologically and cholangiographically by fibro-obliterative inflammation of the bile ducts. In a clinically significant proportion of patients, PSC progresses to cirrhosis, end-stage liver disease, and/or hepatobiliary cancer, though the disease course can be highly variable. Despite clinical trials of numerous pharmacotherapies over several decades, safe and effective medical therapy remains to be established. Liver transplantation is an option for select patients with severe complications of PSC, and its outcomes are generally favorable. Periodic surveillance testing for pre- as well as post-transplant patients is a cornerstone of preventive care and health maintenance. Here we provide an overview of PSC including its epidemiology, etiopathogenesis, clinical features, associated disorders, surveillance, and emerging potential therapies.
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Affiliation(s)
- James H. Tabibian
- Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, USA
- Division of Gastroenterology, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - Christopher L. Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, USA
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40
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Liu K, Strasser SI, Koorey DJ, Leong RW, Solomon M, McCaughan GW. Interactions between primary sclerosing cholangitis and inflammatory bowel disease: implications in the adult liver transplant setting. Expert Rev Gastroenterol Hepatol 2017. [PMID: 28627935 DOI: 10.1080/17474124.2017.1343666] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease which is associated with inflammatory bowel disease (IBD) in most cases. As there is currently no medical therapy which alters the natural history of PSC, liver transplantation may be required. Areas covered: We searched for articles in PubMed and critically reviewed current literature on the interrelationship between PSC and IBD with a specific focus on considerations for patients in the liver transplant setting. Expert commentary: PSC is an uncommon disease which limits available studies to be either retrospective or contain relatively small numbers of patients. Based on observations from these studies, the behavior and complications of PSC and IBD impact on each other both before and after a liver transplant. Both these autoimmune conditions and their associated cancer risk also influence patient selection for transplantation and may be impacted by immunosuppression use post-transplant. Hence, a complex interplay exists between PSC, IBD and liver transplantation which requires clarification with ongoing research.
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Affiliation(s)
- Ken Liu
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia.,c Liver Injury and Cancer Program, Centenary Institute , The University of Sydney , Sydney , NSW , Australia
| | - Simone I Strasser
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - David J Koorey
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - Rupert W Leong
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,d Gastroenterology and Liver Services , Concord Hospital , Sydney , NSW , Australia
| | - Michael Solomon
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,e Department of Colorectal Surgery , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - Geoffrey W McCaughan
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia.,c Liver Injury and Cancer Program, Centenary Institute , The University of Sydney , Sydney , NSW , Australia
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41
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Satapathy SK, Jones OD, Vanatta JM, Kamal F, Kedia SK, Jiang Y, Nair SP, Eason JD. Outcomes of Liver Transplant Recipients With Autoimmune Liver Disease Using Long-Term Dual Immunosuppression Regimen Without Corticosteroid. Transplant Direct 2017; 3:e178. [PMID: 28706981 PMCID: PMC5498019 DOI: 10.1097/txd.0000000000000693] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 04/15/2017] [Accepted: 05/01/2017] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Liver transplant (LT) recipients with autoimmune liver disease (primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis) are at increased risk of developing acute cellular rejection (ACR), and in many cases graft failure due to recurrent disease. We describe our experience with dual immunosuppression without steroid maintenance and analyze its effect on disease recurrence; ACR; patient and graft survivals; and complications, such as sepsis and de novo malignancy. METHODS We included 74 consecutive LT recipients (April 2006 to April 2013) with autoimmune liver disease (primary sclerosing cholangitis, 20; primary biliary cholangitis, 23; autoimmune hepatitis, 31) from a single transplant center. Immunosuppression protocol included rabbit antithymocyte globulin for induction and mycophenolate mofetil with tacrolimus or sirolimus/everolimus indefinitely for maintenance. RESULTS Overall 1-, 3-, 5-, and 7-year patient survival was 95.9%, 90.4%, 82,2% and 74.9%, re-graft-free survival was 93.2%, 86.3%, 79.9%, and 72.8%, respectively (median follow-up, 5.5 years). In a multivariate Cox regression analysis, sepsis during post-LT period (P = 0.040; hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.04-6.11), steroid use for ACR (P = 0.037; HR, 2.60; 95% CI, 1.06-6.34), and younger age (<40 years) at LT (P = 0.038; HR, 2.53; 95% CI, 1.05-6.10) predicted graft survival, whereas steroid use for ACR was the only variable that was predictive of overall patient survival (P = 0.004; HR, 4.10; 95% CI, 1.59-10.52). Overall, 34 biopsy-proven ACR was noted in 22 LT recipients (30%), 13 (17.5%) had disease recurrence, and 34 episodes of sepsis occurred in 19 patients. CONCLUSIONS Dual immunosuppression protocol in LT recipients with autoimmune liver disease without corticosteroid maintenance had acceptable rates of survival and ACR without predisposing patients to the adverse effects of long-term steroid therapy.
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Affiliation(s)
- Sanjaya K. Satapathy
- Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN
| | - Ollie D. Jones
- Department of Gastroenterology, University of Tennessee Health Sciences Center, Memphis, TN
| | - Jason M. Vanatta
- Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN
| | - Faisal Kamal
- Department of Internal Medicine, University of Tennessee Health Sciences Center, Memphis, TN
| | | | - Yu Jiang
- School of Public Health, University of Memphis, Memphis, TN
| | - Satheesh P. Nair
- Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN
| | - James D. Eason
- Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN
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42
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Henson JB, Patel YA, King LY, Zheng J, Chow SC, Muir AJ. Outcomes of liver retransplantation in patients with primary sclerosing cholangitis. Liver Transpl 2017; 23:769-780. [PMID: 28027592 PMCID: PMC5865072 DOI: 10.1002/lt.24703] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Accepted: 12/08/2016] [Indexed: 01/13/2023]
Abstract
Liver retransplantation in patients with primary sclerosing cholangitis (PSC) has not been well studied. The aims of this study were to characterize patients with PSC listed for and undergoing retransplantation and to describe the outcomes in these patients. The United Network for Organ Sharing/Organ Procurement and Transplantation Network database was used to identify all primary liver transplantations and subsequent relistings and first retransplantations in adults with PSC between 1987 and 2015. A total of 5080 adults underwent primary transplantation for PSC during this period, and of the 1803 who experienced graft failure (GF), 762 were relisted, and 636 underwent retransplantation. Younger patients and patients with GF due to vascular thrombosis or biliary complications were more likely to be relisted, whereas those with Medicaid insurance or GF due to infection were less likely. Both 5-year graft and patient survival after retransplantation were inferior to primary transplantation (P < 0.001). Five-year survival after retransplantation for disease recurrence (REC), however, was similar to primary transplantation (graft survival, P = 0.45; patient survival, P = 0.09) and superior to other indications for retransplantation (graft and patient survival, P < 0.001). On multivariate analysis, mechanical ventilation, creatinine, bilirubin, albumin, advanced donor age, and a living donor were associated with poorer outcomes after retransplantation. In conclusion, although survival after liver retransplantation in patients with PSC was overall inferior to primary transplantation, outcomes after retransplantation for PSC REC were similar to primary transplantation at 5 years. Retransplantation may therefore represent a treatment option with the potential for excellent outcomes in patients with REC of PSC in the appropriate clinical circumstances. Liver Transplantation 23 769-780 2017 AASLD.
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Affiliation(s)
| | - Yuval A. Patel
- Division of Gastroenterology, Department of Medicine, Durham, NC
| | - Lindsay Y. King
- Division of Gastroenterology, Department of Medicine, Durham, NC
| | | | - Shein-Chung Chow
- Department of Biostatistics, Durham, NC,Duke Clinical Research Institute, Durham, NC
| | - Andrew J. Muir
- Division of Gastroenterology, Department of Medicine, Durham, NC,Duke Clinical Research Institute, Durham, NC
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43
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Abstract
Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most common cholestatic liver diseases (CLD) in adults. Liver transplant (LT) is desirable for those who progress to end-stage liver disease. CLD have become an uncommon indication for LT. PSC and PBC accounted for 7.1% of all adult LT in 2015. CLD have the best post-LT outcomes compared with other indications for LT. Disease recurrence of PSC and PBC after LT is reported in up to 37% and 43% of LT recipients, respectively. Although recurrent PBC does not affect post-LT outcomes, recurrent PSC is associated with worse post-LT survival.
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Affiliation(s)
- Nathalie A Pena Polanco
- Division of Internal Medicine, Miller School of Medicine, University of Miami, 1611 Northwest 12th Avenue, Suite Central 600-D, Miami, FL 33136, USA
| | - Cynthia Levy
- Division of Hepatology, Miller School of Medicine, University of Miami, 1120 Northwest 14th Street, Suite 1112, Miami, FL 33136, USA
| | - Eric F Martin
- Division of Hepatology, Miller School of Medicine, University of Miami, 1120 Northwest 14th Street, Suite 1112, Miami, FL 33136, USA.
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44
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Larson L, James M, Gossard A. Cholestatic Liver Injury: Care of Patients With Primary Biliary Cholangitis or Primary Sclerosing Cholangitis. AACN Adv Crit Care 2017; 27:441-452. [PMID: 27959300 DOI: 10.4037/aacnacc2016202] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
The most common causes of chronic cholestatic liver disease are primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Both disease processes are characterized by a destruction of intrahepatic and/or extrahepatic biliary ducts. The etiology is not entirely clear; however, there is an underlying autoimmune component contributing to both disease processes. Although PBC and PSC are often diagnosed and managed in the outpatient setting, in some instances, a patient may have jaundice, fatigue, and pruritus requiring evaluation and determination of the cholestatic cause. Patients with PSC should be monitored for evidence of cholangiocarcinoma, colon cancer, and gallbladder polyps as they are at an increased risk of malignant neoplasms. Liver transplant has the potential for improving quality of life, although disease recurrence is a risk.
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Affiliation(s)
- Laurie Larson
- Laurie Larson is Nurse Practitioner, Hepatology, 406 Harvard St SE, MMC 36, University of Minnesota, Minneapolis, MN 55455 . Michelle James is Clinical Director of Transplant Services, University of Minnesota, Minneapolis, Minnesota. Andrea Gossard is Nurse Practitioner, Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Michelle James
- Laurie Larson is Nurse Practitioner, Hepatology, 406 Harvard St SE, MMC 36, University of Minnesota, Minneapolis, MN 55455 . Michelle James is Clinical Director of Transplant Services, University of Minnesota, Minneapolis, Minnesota. Andrea Gossard is Nurse Practitioner, Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Andrea Gossard
- Laurie Larson is Nurse Practitioner, Hepatology, 406 Harvard St SE, MMC 36, University of Minnesota, Minneapolis, MN 55455 . Michelle James is Clinical Director of Transplant Services, University of Minnesota, Minneapolis, Minnesota. Andrea Gossard is Nurse Practitioner, Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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45
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Visseren T, Darwish Murad S. Recurrence of primary sclerosing cholangitis, primary biliary cholangitis and auto-immune hepatitis after liver transplantation. Best Pract Res Clin Gastroenterol 2017. [PMID: 28624107 DOI: 10.1016/j.bpg.2017.04.004] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Liver transplantation is a well-accepted treatment for decompensated chronic liver disease due to primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and auto-immune hepatitis (AIH). Survival after liver transplantation is generally good with 1 and 5-year survival rates around 90% and 70-85%. After transplantation, however, these diseases recur in 8.6-27% (rPSC), 10.9-42.3% (rPBC) and 7-42% (rAIH), and this poses significant challenges in terms of management and graft outcome in these patients. In this review we discuss the incidence, clinical presentation, challenges in diagnosis, reported risk factors and impact on post-transplant outcomes of recurrence of PSC, PBC and AIH after liver transplantation. We also discuss some of the limitations of current investigations and formulate idea's for future research objectives.
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Affiliation(s)
- T Visseren
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
| | - S Darwish Murad
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
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Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients. Clin Gastroenterol Hepatol 2017; 15:584-593.e2. [PMID: 27567694 PMCID: PMC5326609 DOI: 10.1016/j.cgh.2016.07.035] [Citation(s) in RCA: 163] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Accepted: 07/25/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Acute rejection is detrimental to most transplanted solid organs, but is considered to be less of a consequence for transplanted livers. We evaluated risk factors for and outcomes after biopsy-proven acute rejection (BPAR) based on an analysis of a more recent national sample of recipients of liver transplants from living and deceased donors. METHODS We analyzed data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) from 2003 through 2014 as the exploratory cohort and the Scientific Registry of Transplant Recipients (SRTR) from 2005 through 2013 as the validation cohort. We examined factors associated with time to first BPAR using multivariable Cox regression or discrete-survival analysis. Competing risks methods were used to compare causes of death and graft failure between recipients of living and deceased donors. RESULTS At least 1 BPAR episode occurred in 239 of 890 recipients in A2ALL (26.9%) and 7066 of 45,423 recipients in SRTR (15.6%). In each database, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.76; and SRTR HR, 0.78; 95% CI, 0.66-0.91) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each database, BPAR was associated with significantly higher risks of graft failure and death. The risks were highest in the 12 month post-BPAR period in patients whose first episode occurred more than 1 year after liver transplantation: HRs for graft failure were 6.79 in A2ALL (95% CI, 2.64-17.45) and 4.41 in SRTR (95% CI, 3.71-5.23); HRs for death were 8.81 in A2ALL (95% CI, 3.37-23.04) and 3.94 in SRTR (95% CI, 3.22-4.83). In analyses of cause-specific mortality, associations were observed for liver-related (graft failure) causes of death but not for other causes. CONCLUSIONS Contrary to previous data, acute rejection after liver transplant is associated with significantly increased risk of graft failure, all-cause mortality, and graft failure-related death, regardless of primary liver disease etiology. Living donor liver transplantation from a biologically related donor is associated with decreased risk of rejection.
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47
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Montano-Loza AJ, Bhanji RA, Wasilenko S, Mason AL. Systematic review: recurrent autoimmune liver diseases after liver transplantation. Aliment Pharmacol Ther 2017; 45:485-500. [PMID: 27957759 DOI: 10.1111/apt.13894] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 10/21/2016] [Accepted: 11/17/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Autoimmune liver diseases (AILD) constitute the third most common indication for liver transplantation (LT) worldwide. Outcomes post LT are generally good but recurrent disease is frequently observed. AIMS To describe the frequency and risk factors associated with recurrent AILD post-LT and provide recommendations to reduce the incidence of recurrence based on levels of evidence. METHODS A systematic review was performed for full-text papers published in English-language journals, using the keywords 'autoimmune hepatitis (AIH)', 'primary biliary cholangitis and/or cirrhosis (PBC)', 'primary sclerosing cholangitis (PSC)', 'liver transplantation' and 'recurrent disease'. Management strategies to reduce recurrence after LT were classified according to grade and level of evidence. RESULTS Survival rates post-LT are approximately 90% and 70% at 1 and 5 years and recurrent disease occurs in a range of 10-50% of patients with AILD. Recurrent AIH is associated with elevated liver enzymes and IgG before LT, lymphoplasmacytic infiltrates in the explants and lack of steroids after LT (Grade B). Tacrolimus use is associated with increased risk; use of ciclosporin and preventive ursodeoxycholic acid with reduced risk of PBC recurrence (all Grade B). Intact colon, active ulcerative colitis and early cholestasis are associated with recurrent PSC (Grade B). CONCLUSIONS Recommendations based on grade A level of evidence are lacking. The need for further study and management includes active immunosuppression before liver transplantation and steroid use after liver transplantation in autoimmune hepatitis; selective immunosuppression with ciclosporin and preventive ursodeoxycholic acid treatment for primary biliary cholangitis; and improved control of inflammatory bowel disease or even colectomy in primary sclerosing cholangitis.
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Affiliation(s)
- A J Montano-Loza
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - R A Bhanji
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - S Wasilenko
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - A L Mason
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
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Aravinthan AD, Doyle AC, Issachar A, Dib M, Peretz D, Cattral MS, Ghanekar A, McGilvray ID, Selzner M, Greig PD, Grant DR, Selzner N, Lilly LB, Renner EL. First-Degree Living-Related Donor Liver Transplantation in Autoimmune Liver Diseases. Am J Transplant 2016; 16:3512-3521. [PMID: 27088432 DOI: 10.1111/ajt.13828] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Revised: 04/07/2016] [Accepted: 04/08/2016] [Indexed: 01/25/2023]
Abstract
Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post-LT follow-up, were included in this study. Of these, 72 (27%) received a graft from a first-degree living-related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first-degree living-related, living-unrelated, or deceased-donor LT. Similarly, time to recurrence, recurrence-related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first-degree living-related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.
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Affiliation(s)
- A D Aravinthan
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - A C Doyle
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - A Issachar
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - M Dib
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - D Peretz
- Manitoba Liver Transplant Program, University of Manitoba, Winnipeg, Canada
| | - M S Cattral
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - A Ghanekar
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - I D McGilvray
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - M Selzner
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - P D Greig
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - D R Grant
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - N Selzner
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - L B Lilly
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - E L Renner
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada
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49
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Haruki K, Shiba H, Shimada J, Okui N, Iida T, Yanaga K. Complete response to post-transplant lymphoproliferative disorder by surgical resection and rituximab after living-donor liver re-transplantation for recurrent primary sclerosing cholangitis. Clin J Gastroenterol 2016; 10:47-51. [DOI: 10.1007/s12328-016-0698-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 10/19/2016] [Indexed: 12/22/2022]
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50
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Mumtaz S, Goh J, Hirschfield GM, Ferguson J, Cooper SC. Evolving strategies to reduce colectomy rates in primary sclerosing cholangitis-inflammatory bowel disease: clinical remission of corticosteroid refractory colitis post-liver transplant with vedolizumab. Frontline Gastroenterol 2016; 7:271-274. [PMID: 28839868 PMCID: PMC5369500 DOI: 10.1136/flgastro-2016-100711] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease (IBD) in approximately 70% of patients, with ulcerative colitis (UC) being the most common subtype of IBD identified. There is a paucity of data on the optimum management strategy for IBD flares in the post-liver transplant patient, particularly when refractory to conventional treatments. Vedolizumab is a novel gut-specific monoclonal antibody, which has recently been approved for use by National Institute for Health and Care Excellence for moderate-to-severe UC. We present an exemplar case of successful use of vedolizumab in the management of corticosteroid refractory PSC-IBD after liver transplantation.
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Affiliation(s)
- Saqib Mumtaz
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Jason Goh
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Gideon M Hirschfield
- NIHR Liver Biomedical Research Unit, University of Birmingham, Birmingham, UK,Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - James Ferguson
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Sheldon C Cooper
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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