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Zhao X, Naghibzadeh M, Sun Y, Rahmani A, Lilly L, Selzner N, Tsien C, Jaeckel E, Vyas MP, Krishnan R, Hirschfield G, Bhat M. Machine Learning Prediction Model of Waitlist Outcomes in Patients with Primary Sclerosing Cholangitis. Transplant Direct 2025; 11:e1774. [PMID: 40166627 PMCID: PMC11957646 DOI: 10.1097/txd.0000000000001774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 01/01/2025] [Indexed: 04/02/2025] Open
Abstract
Background Liver transplantation is essential for many people with primary sclerosing cholangitis (PSC). People with PSC are less likely to receive a deceased donor liver transplant compared with other causes of chronic liver disease. This disparity may stem from the inaccuracy of the model for end-stage liver disease (MELD) in predicting waitlist mortality or dropout for PSC. The broad applicability of MELD across many causes comes at the expense of accuracy in prediction for certain causes that involve unique comorbidities. We aimed to develop a model that could more accurately predict dynamic changes in waitlist outcomes among patients with PSC while including complex clinical variables. Methods We developed 3 machine learning architectures using data from 4666 patients with PSC in the Scientific Registry of Transplant Recipients (SRTR) and tested our models on our institutional data set of 144 patients at the University Health Network (UHN). We evaluated their time-dependent concordance index (C-index) for mortality prediction and compared it against MELD-sodium and MELD 3.0. Results Random survival forest (RSF), a decision tree-based survival model, outperformed MELD-sodium and MELD 3.0 in both the SRTR and the UHN test data set using the same bloodwork variables and readily available demographic data. It achieved a C-index of 0.868 (SD 0.020) and 0.771 (SD 0.085) on the SRTR and UHN test data, respectively. Training a separate RSF model using the UHN data with PSC-specific achieved a C-index of 0.91. In addition to high MELD score, increased white blood cells, time on the waiting list, platelet count, presence of Autoimmune hepatitis-PSC overlap, aspartate aminotransferase, female sex, age, history of stricture dilation, and extremes of body weight were the top-ranked features predictive of the outcomes. Conclusions Our RSF model offers more accurate waitlist outcome prediction in PSC. The significant performance improvement with the inclusion of PSC-specific variables highlights the importance of disease-specific variables for predicting trajectories of clinically distinct presentations.
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Affiliation(s)
- Xun Zhao
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Maryam Naghibzadeh
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Yingji Sun
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Arya Rahmani
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Leslie Lilly
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Nazia Selzner
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Cynthia Tsien
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Elmar Jaeckel
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | | | - Rahul Krishnan
- Department of Computer Science, University of Toronto, Toronto, ON, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Gideon Hirschfield
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
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Gupta A, Choi S. Diagnosis and Treatment of Extraintestinal Manifestations of Inflammatory Bowel Disease. Surg Clin North Am 2025; 105:385-404. [PMID: 40015823 DOI: 10.1016/j.suc.2024.10.003] [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: 03/01/2025]
Abstract
Inflammatory bowel disease (IBD) is a debilitating disorder that can manifest in many ways and affect multiple organ systems outside the gastrointestinal tract. Extraintestinal manifestations (EIMs) are common in both ulcerative colitis and Crohn's disease and include dermatologic, musculoskeletal, ophthalmologic, and hepatobiliary systems. This study reviews details the most common EIMs of IBD, including their presentation, diagnosis, clinical course, and treatment considerations.
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Affiliation(s)
- Abhinav Gupta
- Department of Surgery, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
| | - Sarah Choi
- Department of Colon and Rectal Surgery, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Suite NTT-7418, Los Angeles, CA 90033, USA.
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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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Molinaro A, Engesæter LK, Jorns C, Nordin A, Rasmussen A, Line PD, Pall V, Ericzon BG, Bennet W, Hov JR, Melum E. Outcome of Liver Retransplantation in Patients With Primary Sclerosing Cholangitis. Liver Int 2025; 45:e16214. [PMID: 39679639 DOI: 10.1111/liv.16214] [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: 05/07/2024] [Revised: 11/27/2024] [Accepted: 12/02/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND AND AIMS Primary sclerosing cholangitis (PSC) is among the most common indications for liver transplantation in the Nordic countries and with an increasing trend in Europe and North America. Due to post-transplant complications and high prevalence of disease recurrence this group is at risk of requiring retransplantation (re-LTX). Results from re-LTX for PSC are not extensively studied and there is a lack of knowledge regarding prognosis after re-LTX in this population. METHODS Graft and patient survival after re-LTX for patients with PSC and a comparable comparison group from the Nordic liver transplant registry were analysed. One-hundred and eighty-five patients with PSC and 208 patients in the comparison group were included. RESULTS The graft and patient survival were better for patients with PSC compared to the comparison group (p < 0.001). Re-LTX for recurrence of PSC (rPSC) compared to other aetiologies had similar and better outcomes for graft and patient survival (p = 0.093 and p = 0.023, respectively). Moreover, re-LTX for rPSC compared to the comparison group had a lower 30-day and 5-year mortality (p < 0.001 and p = 0.041, respectively). CONCLUSION Outcomes after retransplantation for PSC were similar or better compared to the comparison group. Retransplantation represents a treatment option with the potential for excellent outcomes in patients with PSC and should be considered in transplanted PSC patients with graft failure.
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Affiliation(s)
- Antonio Molinaro
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden
- Norwegian PSC Research Center, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway
| | - Lise Katrine Engesæter
- Norwegian PSC Research Center, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway
| | - Carl Jorns
- Division of Transplantation Surgery, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Arno Nordin
- Department of Transplantation and Liver Surgery, University Hospital, Helsinki, Finland
| | - Allan Rasmussen
- Department of Surgical Gastroenterology and Liver Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Pål-Dag Line
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Transplantation Surgery, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
| | - Virge Pall
- Transplantation Centre, Tartu University Hospital, Tartu, Estonia
| | - Bo-Göran Ericzon
- Division of Transplantation Surgery, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - William Bennet
- Transplant Institute, Sahlgrenska University Hospital, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Johannes R Hov
- Norwegian PSC Research Center, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway
| | - Espen Melum
- Norwegian PSC Research Center, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway
- Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway
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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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6
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Angelico R, Siragusa L, Blasi F, Bellato V, Mineccia M, Lolli E, Monteleone G, Sica GS. Colorectal cancer in ulcerative colitis after liver transplantation for primary sclerosing cholangitis: a systematic review and pooled analysis of oncological outcomes. Discov Oncol 2024; 15:529. [PMID: 39378005 PMCID: PMC11461386 DOI: 10.1007/s12672-024-01304-6] [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: 01/14/2024] [Accepted: 09/03/2024] [Indexed: 10/11/2024] Open
Abstract
INTRODUCTION Patients with ulcerative colitis (UC) receiving liver transplantation (LT) due to primary sclerosing cholangitis (PSC) have higher risk of developing colorectal cancers (CRC). Aim of this systematic review was to define the patients' features, immunosuppressive management, and oncological outcomes of LT recipients with UC-PSC developing CRC. METHODS Searches were conducted in PubMed (MEDLINE), Cochrane Library, Web of Science for all English articles published until September 2023. Inclusion criteria were original articles including patients specifying outcomes of interest. Primary endpoints comprised incidence of CRC, disease free survival (DFS), overall survival (OS) and cancer recurrence. Secondary endpoints were patient's and tumor characteristics, graft function, immunosuppressive management and PSC recurrence. PROSPERO CRD42022369190. RESULTS Fifteen studies included, 88 patients were identified. Patients (mean age: 50 years) had a long history of UC (20 years), mainly with active colitis (79%), and developed tumor within the first 3 years from LT, while receiving a double or triple immunosuppressive therapy. Cumulative incidence of tumor was 5.5%. At one, two and three years, DFS was 92%, 82% and 75%, while OS was 87%, 81% and 79% respectively. Disease progression rate was 15%. After CRC surgery, 94% of patients maintained a good graft functionality, with no reported cases of PSC recurrence. CONCLUSIONS After LT, patients with PSC and UC have an increased risk of CRC, especially in presence of long history of UC and active colitis. Surgical resection guarantees satisfactory mid-term oncological outcomes, but samples are limited, and long-term data are lacking. National and international registry are auspicial to evaluate long-term oncological outcomes and to optimize clinical management.
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Affiliation(s)
- Roberta Angelico
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome "Tor Vergata", Rome, Italy
| | - Leandro Siragusa
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
| | - Francesca Blasi
- Minimally Invasive and Digestive Surgery Unit, Department of Surgical Sciences, University of Rome "Tor Vergata", Rome, Italy
| | - Vittoria Bellato
- Minimally Invasive and Digestive Surgery Unit, Department of Surgical Sciences, University of Rome "Tor Vergata", Rome, Italy
| | | | - Elisabetta Lolli
- Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy
| | - Giuseppe S Sica
- Minimally Invasive and Digestive Surgery Unit, Department of Surgical Sciences, University of Rome "Tor Vergata", Rome, Italy.
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Martinez EJ, Pham PH, Wang JF, Stalter LN, Welch BM, Leverson G, Marka N, Al-Qaoud T, Mandelbrot D, Parajuli S, Sollinger HW, Kaufman DB, Redfield RR, Odorico JS. Analysis of Rejection, Infection and Surgical Outcomes in Type I Versus Type II Diabetic Recipients After Simultaneous Pancreas-Kidney Transplantation. Transpl Int 2024; 37:13087. [PMID: 39364120 PMCID: PMC11446817 DOI: 10.3389/ti.2024.13087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 09/10/2024] [Indexed: 10/05/2024]
Abstract
Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HRpancreas = 1.04, p = 0.93; HRkidney = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (ppancreas = 0.57; pkidney = 0.41). T2D had a significantly lower incidence of de novo DSA at 1 year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients.
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Affiliation(s)
- Eric J. Martinez
- Anette C and Harold C Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Phuoc H. Pham
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
- Department of Medicine, School of Medicine, Creighton University, Omaha, NE, United States
| | - Jesse F. Wang
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Lily N. Stalter
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Bridget M. Welch
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Glen Leverson
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Nicholas Marka
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Talal Al-Qaoud
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Hans W. Sollinger
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Dixon B. Kaufman
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Robert R. Redfield
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Jon Scott Odorico
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
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8
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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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Komi M, Kawanaka M, Kimura M, Oda S, Shimada K, Kawada M, Ishii K, Tanikawa T, Urata N, Nishino K, Suehiro M, Haruma K, Nagai K, Hatano E, Kawamoto H. A case of primary sclerosing cholangitis with no recurrence and a good outcome for more than 20 years after living donor liver transplantation. KANZO 2024; 65:66-73. [DOI: 10.2957/kanzo.65.66] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Affiliation(s)
- Masahiro Komi
- Department of Postgraduate Training Center, Kawasaki Medical Center, Kawasaki Medical School
| | - Miwa Kawanaka
- Department of General Internal Medicine2, Kawasaki Medical School
| | - Minako Kimura
- Department of General Internal Medicine2, Kawasaki Medical School
| | - Shintaro Oda
- Department of General Internal Medicine2, Kawasaki Medical School
| | - Keisuke Shimada
- Department of General Internal Medicine2, Kawasaki Medical School
| | - Mayuko Kawada
- Department of General Internal Medicine2, Kawasaki Medical School
| | - Katsunori Ishii
- Department of General Internal Medicine2, Kawasaki Medical School
| | | | - Noriyo Urata
- Department of General Internal Medicine2, Kawasaki Medical School
| | - Ken Nishino
- Department of General Internal Medicine2, Kawasaki Medical School
| | | | - Ken Haruma
- Department of General Internal Medicine2, Kawasaki Medical School
| | - Kazuyuki Nagai
- Department of Surgery, Graduate School of Medicine, Kyoto University
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University
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Takahashi K, Ohyama H, Ohno I, Takiguchi Y, Kato N. A Case of Primary Sclerosing Cholangitis Complicated With Liver Abscess Caused by Hyperviscous Klebsiella pneumoniae. Cureus 2023; 15:e51277. [PMID: 38283418 PMCID: PMC10822113 DOI: 10.7759/cureus.51277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/28/2023] [Indexed: 01/30/2024] Open
Abstract
Liver abscesses caused by Klebsiella pneumoniae with a positive string test for hyperviscosity are more likely to develop invasive conditions than those with a negative string test. Here, we report the case of primary sclerosing cholangitis (PSC) who developed a treatment-resistant liver abscess caused by hyperviscous Klebsiella pneumoniae. A 67-year-old woman with PSC and a history of pancreaticoduodenectomy developed a fever. She had recurrent bacterial cholangitis after pancreaticoduodenectomy. This time, she was diagnosed with a liver abscess and bacterial cholangitis and then admitted to a local hospital. As her condition did not improve with intravenous administration of meropenem, she was transferred from another hospital to our hospital on the 7th day of admission. The percutaneous transhepatic abscess drainage was performed, and intravenous administration of cefepime and metronidazole was started. Klebsiella pneumoniae with a positive string test was detected in the blood culture test and the pus culture of the liver abscess. Although the liver abscess was reduced in size, the infection did not subside completely. Her general condition gradually deteriorated. She passed away on the 45th day of illness. In PSC patients, the formation of a liver abscess caused by hyperviscous Klebsiella pneumoniae can be life-threatening. In such cases, pus should be collected as soon as possible to identify the causative bacteria.
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Affiliation(s)
- Koji Takahashi
- Gastroenterology, Chiba University, Chiba, JPN
- Medical Oncology, Chiba University, Chiba, JPN
| | | | - Izumi Ohno
- Gastroenterology, Chiba University, Chiba, JPN
- Medical Oncology, Chiba University, Chiba, JPN
| | | | - Naoya Kato
- Gastroenterology, Chiba University, Chiba, JPN
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11
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Harputluoglu M, Calgin MZ, Ataman E, Tikici D, Kutluturk K, Kutlu R, Efe CS, Yilmaz S. Outcomes of patients with primary sclerosing cholangitis after liver transplantation in a predominantly living donor liver transplant center. JOURNAL OF LIVER TRANSPLANTATION 2023; 12:100186. [DOI: 10.1016/j.liver.2023.100186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2025] Open
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12
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Tan N, Lubel J, Kemp W, Roberts S, Majeed A. Current Therapeutics in Primary Sclerosing Cholangitis. J Clin Transl Hepatol 2023; 11:1267-1281. [PMID: 37577219 PMCID: PMC10412694 DOI: 10.14218/jcth.2022.00068s] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 01/01/2023] [Accepted: 01/20/2023] [Indexed: 07/03/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is an orphan, cholestatic liver disease that is characterized by inflammatory biliary strictures with variable progression to end-stage liver disease. Its pathophysiology is poorly understood. Chronic biliary inflammation is likely driven by immune dysregulation, gut dysbiosis, and environmental exposures resulting in gut-liver crosstalk and bile acid metabolism disturbances. There is no proven medical therapy that alters disease progression in PSC, with the commonly prescribed ursodeoxycholic acid being shown to improve liver biochemistry at low-moderate doses (15-23 mg/kg/day) but not alter transplant-free survival or liver-related outcomes. Liver transplantation is the only option for patients who develop end-stage liver disease or refractory complications of PSC. Immunosuppressive and antifibrotic agents have not proven to be effective, but there is promise for manipulation of the gut microbiome with fecal microbiota transplantation and antibiotics. Bile acid manipulation via alternate synthetic bile acids such as norursodeoxycholic acid, or interaction at a transcriptional level via nuclear receptor agonists and fibrates have shown potential in phase II trials in PSC with several leading to larger phase III trials. In view of the enhanced malignancy risk, statins, and aspirin show potential for reducing the risk of colorectal cancer and cholangiocarcinoma in PSC patients. For patients who develop clinically relevant strictures with cholestatic symptoms and worsening liver function, balloon dilatation is safer compared with biliary stent insertion with equivalent clinical efficacy.
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Affiliation(s)
- Natassia Tan
- Department of Gastroenterology and Hepatology, Alfred Health; Central Clinical School, Monash University, Melbourne, Australia
| | - John Lubel
- Department of Gastroenterology and Hepatology, Alfred Health; Central Clinical School, Monash University, Melbourne, Australia
| | - William Kemp
- Department of Gastroenterology and Hepatology, Alfred Health; Central Clinical School, Monash University, Melbourne, Australia
| | - Stuart Roberts
- Department of Gastroenterology and Hepatology, Alfred Health; Central Clinical School, Monash University, Melbourne, Australia
| | - Ammar Majeed
- Department of Gastroenterology and Hepatology, Alfred Health; Central Clinical School, Monash University, Melbourne, Australia
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13
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Wiederkehr HDA, Wiederkehr JC, Da Igreja MR, Ramos EB, Nogara MS, Soffiatti DS, Massutti A, Sasaki VL, Wiederkehr BDA, Valejo IRM, Coelho JCU. LIVER TRANSPLANTATION IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS: A MULTICENTRIC STUDY. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2023; 36:e1769. [PMID: 37851755 PMCID: PMC10578153 DOI: 10.1590/0102-672020230051e1769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 08/17/2023] [Indexed: 10/20/2023]
Abstract
BACKGROUND The prevalence of primary sclerosing cholangitis (PSC) in the general population has not yet been clearly established. The management of PSC should focus on delaying the progression of the disease and restraining its complications. The only curative therapy for the disease remains liver transplantation (LT). PSC is currently the fifth most common indication for LT and corresponds to 5% of all LT indications in adults. AIMS Our objective is to evaluate the indications and outcomes of PSC patients undergoing LT in three liver transplantation centers in southern Brazil - Hospital Santa Isabel in Blumenau, Santa Catarina state, and Hospital das Clínicas and Hospital Nossa Senhora das Graças, in Curitiba, Parana state). METHODS This is a longitudinal observational study of patients with PSC who underwent LT in three major Brazilian medical centers. Electronic medical records and study protocols of all patients subjected to LT from January 2011 to December 2021 were retrospectively reviewed. RESULTS Of the 1,362 transplants performed in the three medical centers, 37 were due to PSC. Recurrence of PSC occurred in three patients (8.1%) in 3.0±2.4 years (range, 1-4 years). The 1-year and 5-year survival rates after the first LT were 83.8 and 80.6%, respectively. The 1-year and 5-year graft survival rates were, respectively, 83.8 and 74.8%. CONCLUSIONS Our experience with LT in patients with PSC demonstrated good patient and graft survival results. Most deaths were due to common factors in patients undergoing LT.
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Affiliation(s)
| | - Julio Cesar Wiederkehr
- Universidade Federal do Paraná, University Hospital, Liver Transplant Department, Curitiba (PR), Brazil
- Santa Isabel Hospital, Liver Transplant Department, Blumenau (SC), Brasil
| | | | | | | | | | - Andrew Massutti
- Santa Isabel Hospital, Liver Transplant Department, Blumenau (SC), Brasil
| | - Vivian Laís Sasaki
- Nossa Senhora das Graças Hospital, Liver Transplant Department, Curitiba (PR), Brazil
| | | | | | - Júlio Cezar Uili Coelho
- Universidade Federal do Paraná, University Hospital, Liver Transplant Department, Curitiba (PR), Brazil
- Nossa Senhora das Graças Hospital, Liver Transplant Department, Curitiba (PR), Brazil
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14
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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: 0] [Impact Index Per Article: 0] [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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15
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Onofrio F, Zheng K, Xu C, Chen S, Xu W, Vyas M, Bingham K, Patel K, Lilly L, Cattral M, Selzner N, Jaeckel E, Tsien C, Gulamhusein A, Hirschfield GM, Bhat M. Living donor liver transplantation can address disparities in transplant access for patients with primary sclerosing cholangitis. Hepatol Commun 2023; 7:e0219. [PMID: 37534935 PMCID: PMC10552969 DOI: 10.1097/hc9.0000000000000219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 05/04/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Liver transplantation (LT) is frequently lifesaving for people living with primary sclerosing cholangitis (PSC). However, patients are waitlisted for LT according to the model for end-stage liver disease-sodium (MELD-Na) score, which may not accurately reflect the burden of living with PSC. We sought to describe and analyze the clinical trajectory for patients with PSC referred for LT, in a mixed deceased donor/living donor transplant program. METHODS This was a retrospective cohort study from November 2012 to December 2019, including all patients with PSC referred for assessment at the University Health Network Liver Transplant Clinic. Patients who required multiorgan transplant or retransplantation were excluded. Liver symptoms, hepatobiliary malignancy, MELD-Na progression, and death were abstracted from chart review. Competing risk analysis was used for timing of LT, transplant type, and death. RESULTS Of 172 PSC patients assessed, 84% (n = 144) were listed of whom 74% were transplanted. Mean age was 47.6 years, and 66% were male. Overall mortality was 18.2% at 2 years. During the follow-up, 16% (n = 23) were removed from the waitlist for infection, clinical deterioration, liver-related mortality or new cancer; 3 had clinical improvement. At listing, 82% (n = 118) had a potential living donor (pLD). Patients with pLD had significantly lower waitlist and liver-related waitlist mortality (HR 0.20, p<0.001 and HR 0.17, p<0.001, respectively), and higher rates of transplantation (HR 1.83, p = 0.05). Exception points were granted to 13/172 (7.5%) patients. CONCLUSIONS In a high-volume North American LT center, most patients with PSC assessed for transplant were listed and subsequently transplanted. However, this was a consequence of patients engaging in living donor transplantation. Our findings support the concern from patients with PSC that MELD-Na allocation does not adequately address their needs.
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Affiliation(s)
- Fernanda Onofrio
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Katina Zheng
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Cherry Xu
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Shiyi Chen
- Biostatistics Department, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada
| | - Wei Xu
- Biostatistics Department, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada
| | | | | | - Keyur Patel
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Leslie Lilly
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Mark Cattral
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Nazia Selzner
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Elmar Jaeckel
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Cynthia Tsien
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Aliya Gulamhusein
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada
| | - Gideon M. Hirschfield
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada
| | - Mamatha Bhat
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada
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16
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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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17
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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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18
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Do Patients with Autoimmune Conditions Have Less Access to Liver Transplantation despite Superior Outcomes? J Pers Med 2022; 12:jpm12071159. [PMID: 35887656 PMCID: PMC9320508 DOI: 10.3390/jpm12071159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/13/2022] [Accepted: 07/14/2022] [Indexed: 11/17/2022] Open
Abstract
Orthotopic liver transplantation (OLT) is a lifesaving therapy for patients with irreversible liver damage caused by autoimmune liver diseases (AutoD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, it is unclear how access to transplantation differs among patients with various etiologies of liver disease. Our aim is to evaluate the likelihood of transplant and the long-term patient and graft survival after OLT for each etiology for transplantation from 2000 to 2021. We conducted a large retrospective study of United Network for Organ Sharing (UNOS) liver transplant patients in five 4-year eras with five cohorts: AutoD (PBC, PSC, AIH cirrhosis), alcohol-related liver disease (ALD), hepatocellular carcinoma (HCC), viral hepatitis, and nonalcoholic steatohepatitis (NASH). We conducted a multivariate analysis for probability of transplant. Intent-to-treat (ITT) analysis was performed to assess the 10-year survival differences for each listing diagnosis while accounting for both waitlist and post-transplant survival. Across all eras, autoimmune conditions had a lower adjusted probability of transplant of 0.92 (0.92, 0.93) compared to ALD 0.97 (0.97, 0.97), HCC 1.08 (1.07, 1.08), viral hepatitis 0.99 (0.99, 0.99), and NASH 0.99 (0.99, 1.00). Patients with AutoD had significantly better post-transplant patient and graft survival than ALD, HCC, viral hepatitis, and NASH in each and across all eras (p-values all < 0.001). Patients with AutoD had superior ITT survival (p-value < 0.001, log rank test). In addition, the waitlist survival for patients with AutoD compared to other listing diagnoses was improved with the exception of ALD, which showed no significant difference (p-value = 0.1056, log rank test). Despite a superior 10-year graft and patient survival in patients transplanted for AutoD, patients with AutoD have a significantly lower probability of receiving a liver transplant compared to those transplanted for HCC, ALD, viral hepatitis, and NASH. Patients with AutoD may benefit from improved liver allocation while maintaining superior waitlist and post-transplant survival. Decreased access in spite of appropriate outcomes for patients poses a significant risk for increased morbidity for patients with AutoD.
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19
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Safarpour AR, Shojaei-Zarghani S, Mehrabi M, Keshtkar AA, Oroojan AA, Sivandzadeh GR. Alterations in the Course of Inflammatory Bowel Disease Following Liver Transplantation: A Systematic Review and Meta-analysis. Inflamm Bowel Dis 2022:6627524. [PMID: 35779047 DOI: 10.1093/ibd/izac132] [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: 02/28/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND This study aimed to systematically review and pool data regarding the alterations in the clinical course of inflammatory bowel disease (IBD) following liver transplantation (LT). METHODS Relevant prospective and retrospective observational studies were identified by searching databases and gray literature through December 2020. Random-effects models were used to calculate the pooled frequency of IBD patients with disease course alterations ("improved," "unchanged," or "aggravated") after LT and the corresponding 95% confidence intervals (CIs). RESULTS Twenty-five studies met our inclusion criteria, reporting the outcomes in 2 or 3 categories. In the analysis of studies with 3-category outcomes (n = 13), the pooled frequencies of patients with improved, unchanged, or aggravated IBD course after LT were 29.4% (95% CI, 16.9% to 41.9%), 51.4% (95% CI, 45.5% to 57.3%), and 25.2% (95% CI, 15.6% to 34.8%), respectively. Subgroup analyses revealed that patients with ulcerative colitis (UC), younger age at LT, or shorter duration of follow-up were more likely to have an improved disease course. Moreover, higher IBD exacerbation estimates were observed in studies with a low risk of bias. In the analysis of studies with 2-category outcomes (n = 12), the pooled frequencies of patients with improved/unchanged or aggravated IBD course were 73.6% (95% CI, 62.2% to 85.0%) and 24.1% (95% CI, 15.1% to 33.2%), respectively. The cumulative incidence of an exacerbated IBD course following LT was 0.22 (95% CI, 0.16-0.29; P < .001). CONCLUSION We conclude that IBD activity remains unchanged (or improved/unchanged) in most IBD patients following LT. Furthermore, IBD type, age, and follow-up length can influence the IBD course after LT.
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Affiliation(s)
- Ali Reza Safarpour
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sara Shojaei-Zarghani
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Manoosh Mehrabi
- Department of E-Learning, Virtual school, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Abbas Ali Keshtkar
- Department of Health Sciences Education Development, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Akbar Oroojan
- Department of Physiology, Faculty of Medicine, Dezful University of Medical Sciences, Dezful, Iran
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20
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Goel A, Kwong A. CAQ Corner: Disease recurrence after liver transplantation. Liver Transpl 2022:1. [PMID: 37160054 DOI: 10.1002/lt.26492] [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: 02/23/2022] [Revised: 04/09/2022] [Accepted: 04/20/2022] [Indexed: 02/07/2023]
Affiliation(s)
- Aparna Goel
- Division of Gastroenterology/Hepatology, Stanford University, Palo Alto, California, USA
| | - Allison Kwong
- Division of Gastroenterology/Hepatology, Stanford University, Palo Alto, California, USA
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21
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Nguyen CM, Kline KT, Stevenson HL, Khan K, Parupudi S. Small duct primary sclerosing cholangitis: A discrete variant or a bridge to large duct disease, a practical review. World J Hepatol 2022; 14:495-503. [PMID: 35582290 PMCID: PMC9055190 DOI: 10.4254/wjh.v14.i3.495] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/12/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
The natural history, associations with inflammatory bowel disease (IBD), and long-term outcomes of large duct primary sclerosing cholangitis (ldPSC) have been well documented. Small duct primary sclerosing cholangitis (sdPSC) is a much less common and relatively more benign variant. The natural history of sdPSC has been difficult to characterize given the limited number of studies in the literature especially with regards to the subset of patients who progress to large duct involvement. It has been unclear whether sdPSC represented a subset of ldPSC, an earlier staging of ldPSC, or a completely separate and distinct entity of its own. Strong associations between sdPSC and IBD have been established with suspicion that concurrent sdPSC-IBD may be a key prognostic factor in determining which patients are at risk of progression to ldPSC. Little is known regarding the discrete circumstances that predisposes some patients with sdPSC to progress to ldPSC. It has been suspected that progression to large biliary duct involvement subjects this subset of patients to potentially developing life-threatening complications. Here the authors conducted a thorough review of the published sdPSC literature using Pubmed searches and cross-referencing to compile all accessible studies regarding cohorts of sdPSC patients in order better characterize the subset of sdPSC patients who progress to ldPSC and the associated outcomes.
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Affiliation(s)
- Christopher M Nguyen
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555, United States
| | - Kevin T Kline
- Department of Gastroenterology and Hepatology, The University of Texas Medical Branch, Galveston, TX 77555, United States
| | - Heather L Stevenson
- Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, United States
| | - Kashif Khan
- Department of Gastroenterology and Hepatology, The University of Texas Medical Branch, Galveston, TX 77555, United States
| | - Sreeram Parupudi
- Department of Gastroenterology and Hepatology, The University of Texas Medical Branch, Galveston, TX 77555, United States
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22
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Nakamura T, Shirouzu T. Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants. J Clin Med 2021; 10:5417. [PMID: 34830699 PMCID: PMC8619797 DOI: 10.3390/jcm10225417] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/17/2021] [Accepted: 11/18/2021] [Indexed: 02/08/2023] Open
Abstract
The advances in acute phase care have firmly established the practice of organ transplantation in the last several decades. Then, the next issues that loom large in the field of transplantation include antibody-mediated rejection (ABMR) and recurrent primary disease. Acute ABMR is a daunting hurdle in the performance of organ transplantation. The recent progress in desensitization and preoperative monitoring of donor-specific antibodies enables us to increase positive outcomes. However, chronic active ABMR is one of the most significant problems we currently face. On the other hand, recurrent primary disease is problematic for many recipients. Notably, some recipients, unfortunately, lost their vital organs due to this recurrence. Although some progress has been achieved in these two areas, many other factors remain largely obscure. In this review, these two topics will be discussed in light of recent discoveries.
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Affiliation(s)
- Tsukasa Nakamura
- Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Takayuki Shirouzu
- Molecular Diagnositcs Division, Wakunaga Pharmaceutical Co., Ltd., 13-4 Arakicho, shinjyuku-ku, Tokyo 160-0007, Japan;
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23
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Patel AM, Liu YS, Davies SP, Brown RM, Kelly DA, Scheel-Toellner D, Reynolds GM, Stamataki Z. The Role of B Cells in Adult and Paediatric Liver Injury. Front Immunol 2021; 12:729143. [PMID: 34630404 PMCID: PMC8495195 DOI: 10.3389/fimmu.2021.729143] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 08/16/2021] [Indexed: 12/16/2022] Open
Abstract
B lymphocytes are multitasking cells that direct the immune response by producing pro- or anti-inflammatory cytokines, by presenting processed antigen for T cell activation and co-stimulation, and by turning into antibody-secreting cells. These functions are important to control infection in the liver but can also exacerbate tissue damage and fibrosis as part of persistent inflammation that can lead to end stage disease requiring a transplant. In transplantation, immunosuppression increases the incidence of lymphoma and often this is of B cell origin. In this review we bring together information on liver B cell biology from different liver diseases, including alcohol-related and metabolic fatty liver disease, autoimmune hepatitis, primary biliary and primary sclerosing cholangitis, viral hepatitis and, in infants, biliary atresia. We also discuss the impact of B cell depletion therapy in the liver setting. Taken together, our analysis shows that B cells are important in the pathogenesis of liver diseases and that further research is necessary to fully characterise the human liver B cell compartment.
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Affiliation(s)
- Arzoo M. Patel
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Yuxin S. Liu
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Scott P. Davies
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Rachel M. Brown
- Department of Histopathology, Queen Elizabeth Hospital, Birmingham Women’s and Children’s National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
| | - Deirdre A. Kelly
- The Liver Unit, Birmingham Women’s and Children’s Hospital and the University of Birmingham, Birmingham, United Kingdom
| | - Dagmar Scheel-Toellner
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Gary M. Reynolds
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- The Liver Unit, Birmingham Women’s and Children’s Hospital and the University of Birmingham, Birmingham, United Kingdom
| | - Zania Stamataki
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
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24
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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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25
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Mawardi M, Alalwan A, Fallatah H, Abaalkhail F, Hasosah M, Shagrani M, Alghamdi MY, Alghamdi AS. Cholestatic liver disease: Practice guidelines from the Saudi Association for the Study of Liver diseases and Transplantation. Saudi J Gastroenterol 2021; 27:S1-S26. [PMCID: PMC8411950 DOI: 10.4103/sjg.sjg_112_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/26/2021] [Accepted: 05/16/2021] [Indexed: 11/04/2022] Open
Abstract
Cholestatic liver diseases (CLDs) are a group of diseases characterized by jaundice and cholestasis as the main presentation with different complications, which have considerable impact on the liver and can lead to end-stage liver disease, cirrhosis, and liver-related complications. In the last few years, tremendous progress has been made in understanding the pathophysiology, diagnosis, and treatment of patients with these conditions. However, several aspects related to the management of CLDs remain deficient and unclear. Due to the lack of recommendations that can help in the management, treatment of those conditions, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) has created a task force group to develop guidelines related to CLDs management in order to provide a standard of care for patients in need. These guidelines provide general guidance for health care professionals to optimize medical care for patients with CLDs for both adult and pediatric populations, in association with clinical judgments to be considered on a case-by-case basis. These guidelines describe common CLDs in Saudi Arabia, with recommendations on the best approach for diagnosis and management of different diseases based on the Grading of Recommendation Assessment (GRADE), combined with a level of evidence available in the literature.
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Affiliation(s)
- Mohammad Mawardi
- Department of Medicine, Gastroenterology Section, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia
| | - Abduljaleel Alalwan
- Department of Hepatobiliary Sciences and Liver Transplantation, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Hind Fallatah
- Department of Medicine, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Gastroenterology Section, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Mohammed Hasosah
- Department of Pediatrics, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Mohammad Shagrani
- Department of Liver and Small Bowel Transplantation, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Mohammed Y Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahd Military Complex, Dhahran, Saudi Arabia
| | - Abdullah S Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahad General Hospital, Jeddah, Saudi Arabia
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26
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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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27
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Couchonnal E, Jacquemin E, Lachaux A, Ackermann O, Gonzales E, Lacaille F, Debray D, Boillot O, Guillaud O, Wildhaber BE, Chouik Y, McLin V, Dumortier J. Long-term results of pediatric liver transplantation for autoimmune liver disease. Clin Res Hepatol Gastroenterol 2021; 45:101537. [PMID: 33077391 DOI: 10.1016/j.clinre.2020.08.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/19/2020] [Accepted: 08/26/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are rare indications for liver transplantation (LT) in children. The aim of the present retrospective multicenter study was to evaluate long-term outcome after LT for autoimmune liver disease in childhood. METHODS Retrospective data from 30 children who underwent a first LT from 1988 to 2018 were collected. RESULTS The study population consisted of 18 girls and 12 boys, transplanted for AIH type 1 (n=14), AIH type 2 (n=7) or PSC (n=9). Mean age at LT was 11.8±5.2 years. The main indications for LT were acute (36.7%) or chronic end-stage liver failure (63.3%). Graft rejection occurred in 19 patients (63.3%); 6 pts required retransplantation for chronic rejection. Recurrence of initial disease was observed in 6 patients (20.0%), all of them with type 1 AIH, after a median time of 42 months, requiring retransplantation in 2 cases. Overall patient survival rates were 96.4%, 84.6%, 74.8%, 68.0%, 68.0%, 68.0% and 68.0% at 1, 5, 10, 15, 20, 25 and 30 years, respectively. Age at LT<1year (p<0.0001), LT for fulminant failure (p=0.023) and LT for type 2 AIH (p=0.049) were significant predictive factors of death. CONCLUSION Long-term outcome after LT for pediatric autoimmune liver disease is impaired in patients with AIH because of consistent complications such as rejection and disease recurrence.
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Affiliation(s)
- Eduardo Couchonnal
- Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service d'Hépato-gastroentérologie et Nutrition Pédiatrique, Bron, France
| | - Emmanuel Jacquemin
- Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Hépatologie et Transplantation Hépatique Pédiatriques, Centre National de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, Université Paris Saclay, Le Kremlin-Bicêtre, France; Inserm U1193, Hepatinov, Université Paris Saclay, Orsay, France
| | - Alain Lachaux
- Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service d'Hépato-gastroentérologie et Nutrition Pédiatrique, Bron, France; Centre National de Référence de l'Atrésie des Voies biliaires et des Cholestases Génétiques de Lyon, France; Université Claude Bernard Lyon 1, Lyon, France
| | - Oanez Ackermann
- Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Hépatologie et Transplantation Hépatique Pédiatriques, Centre National de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, Université Paris Saclay, Le Kremlin-Bicêtre, France; Inserm U1193, Hepatinov, Université Paris Saclay, Orsay, France
| | - Emmanuel Gonzales
- Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Hépatologie et Transplantation Hépatique Pédiatriques, Centre National de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, Université Paris Saclay, Le Kremlin-Bicêtre, France; Inserm U1193, Hepatinov, Université Paris Saclay, Orsay, France
| | - Florence Lacaille
- Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants malades, Unité d'Hépatologie pédiatrique, Centre de référence de l'Atrèsie des voies biliaires et cholestases génétiques, filière de santé Filfoie, Paris, France
| | - Dominique Debray
- Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants malades, Unité d'Hépatologie pédiatrique, Centre de référence de l'Atrèsie des voies biliaires et cholestases génétiques, filière de santé Filfoie, Paris, France; Université-Paris centre, Paris, France
| | - Olivier Boillot
- Université Claude Bernard Lyon 1, Lyon, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, Femme-Mère-Enfant, Service d'Hépato-gastroentérologie, Lyon, France
| | - Olivier Guillaud
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Femme-Mère-Enfant, Service d'Hépato-gastroentérologie, Lyon, France; Ramsay Générale de Santé, Clinique de la Sauvegarde, Lyon, France
| | - Barbara E Wildhaber
- Swiss Pediatric Liver Center, Department of Pediatrics, Gynecology, and Obstetrics, University Hospitals Geneva, University of Geneva, Geneva, Switzerland
| | - Yasmina Chouik
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Femme-Mère-Enfant, Service d'Hépato-gastroentérologie, Lyon, France
| | - Valérie McLin
- Swiss Pediatric Liver Center, Department of Pediatrics, Gynecology, and Obstetrics, University Hospitals Geneva, University of Geneva, Geneva, Switzerland
| | - Jérôme Dumortier
- Université Claude Bernard Lyon 1, Lyon, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, Femme-Mère-Enfant, Service d'Hépato-gastroentérologie, Lyon, France.
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28
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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] [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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29
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Bayable A, Ohabughiro M, Cheung R, Wong RJ. Ethnicity-Specific Differences in Liver Transplant Outcomes Among Adults With Primary Sclerosing Cholangitis: 2005-2017 United Network for Organ Sharing/Organ Procurement and Transplantation Network. J Clin Exp Hepatol 2021; 11:30-36. [PMID: 33679046 PMCID: PMC7897847 DOI: 10.1016/j.jceh.2020.06.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 06/05/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND & AIMS Lack of effective medical therapies for primary sclerosing cholangitis (PSC) leads to continued disease progression to end-stage liver disease requiring liver transplantation (LT). Few studies have specifically evaluated whether ethnic disparities in LT outcomes exist among adults awaiting LT. We aimed to evaluate ethnicity-specific differences in LT outcomes among adults with PSC in the US. METHODS We retrospectively evaluated US adults (aged ≥ 18 years) with PSC without hepatocellular carcinoma listed for LT using the 2005-2017 United Network for Organ Sharing database. Ethnicity-specific differences in overall waitlist survival and probability of receiving LT were evaluated using competing risks regression analyses and adjusted multivariable Cox proportional hazards models. Overall survival after LT was evaluated with Kaplan-Meier methods and multivariable Cox proportional hazards models. RESULTS Among 4046 patients with PSC listed for LT (69.2% men, 82.2% non-Hispanic white, 12.4% African American, 3.9% Hispanic, 1.6% Asian), significantly higher risk of waitlist death was men vs. women (Standardized hazard ratio (SHR) = 1.50, 95% CI: 1.05-2.12, P = 0.025), but no ethnicity-specific differences were observed. Compared with non-Hispanic whites, Hispanics had significantly lower probability of receiving LT (SHR = 0.73, 95% CI: 0.54-0.98, P = 0.035). Among patients with PSC and end-stage liver disease who underwent LT, African Americans had significantly higher risk of post-LT death compared with non-Hispanic whites (SHR = 1.68, 95% CI: 1.21-2.32, P = 0.002). CONCLUSIONS Among a large cohort of US adults with PSC awaiting LT, significant ethnicity-specific disparities in LT outcomes were observed. Lower probability of LT in Hispanics and significantly higher risk of post-LT death in African Americans were observed.
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Key Words
- ESLD, End-Stage Liver Disease
- HCC, Hepatocellular Carcinoma
- HE, Hepatic Encephalopathy
- HR, Hazards Ratio
- IBD, Inflammatory Bowel Disease
- LT, Liver Transplantation
- MELD, Model for End-Stage Liver Disease
- PSC, Primary Sclerosing Cholangitis
- UNOS, United Network for Organ Sharing
- UNOS/OPTN
- WL, Waitlist
- ethnicity
- liver transplantation
- primary sclerosing cholangitis
- survival
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Affiliation(s)
- Asnakech Bayable
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - Michael Ohabughiro
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA,Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Robert J. Wong
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA,Address for correspondence. Robert J. Wong, Division of Gastroenterology and Hepatology Alameda Health System – Highland Hospital 1411 East 31st Street Highland Hospital – Highland Care Pavilion 5th Floor Endoscopy Unit Oakland, CA, 94602, USA.
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30
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Peverelle M, Paleri S, Hughes J, De Cruz P, Gow PJ. Activity of Inflammatory Bowel Disease After Liver Transplantation for Primary Sclerosing Cholangitis Predicts Poorer Clinical Outcomes. Inflamm Bowel Dis 2020; 26:1901-1908. [PMID: 31944235 DOI: 10.1093/ibd/izz325] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND The impact of inflammatory bowel disease (IBD) activity on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is unknown. We examined the impact of post-LT IBD activity on clinically significant outcomes. METHODS One hundred twelve patients undergoing LT for PSC from 2 centers were studied for a median of 7 years. Patients were divided into 3 groups according to their IBD activity after LT: no IBD, mild IBD, and moderate to severe IBD. Patients were classified as having moderate to severe IBD if they met at least 1 of 3 criteria: (i) Mayo 2 or 3 colitis or Simple Endoscopic Score-Crohn's Disease ≥7 on endoscopy; (ii) acute flare of IBD necessitating steroid rescue therapy; or (iii) post-LT colectomy for medically refractory IBD. RESULTS Moderate to severe IBD at any time post-transplant was associated with a higher risk of Clostridium difficile infection (27% vs 8% mild IBD vs 8% no IBD; P = 0.02), colorectal cancer/high-grade dysplasia (21% vs 3% both groups; P = 0.004), post-LT colectomy (33% vs 3% vs 0%) and rPSC (64% vs 18% vs 20%; P < 0.001). Multivariate analysis revealed that moderate to severe IBD increased the risk of both rPSC (relative risk [RR], 8.80; 95% confidence interval [CI], 2.81-27.59; P < 0.001) and colorectal cancer/high-grade dysplasia (RR, 10.45; 95% CI, 3.55-22.74; P < 0.001). CONCLUSIONS Moderate to severe IBD at any time post-LT is associated with a higher risk of rPSC and colorectal neoplasia compared with mild IBD and no IBD. Patients with no IBD and mild IBD have similar post-LT outcomes. Future prospective studies are needed to determine if more intensive treatment of moderate to severe IBD improves long-term outcomes in patients undergoing LT for PSC.
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Affiliation(s)
| | - Sarang Paleri
- Liver Transplant Unit, Heidelberg, Victoria, Australia
| | - Jed Hughes
- Liver Transplant Unit, Heidelberg, Victoria, Australia
| | - Peter De Cruz
- Department of Gastroenterology, Austin Health, Heidelberg, Victoria, Australia.,Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - Paul J Gow
- Liver Transplant Unit, Heidelberg, Victoria, Australia.,Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
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31
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Irlès-Depé M, Roullet S, Neau-Cransac M, Dumortier J, Dharancy S, Houssel-Debry P, Boillot O, Chiche L, Laurent C, Laharie D, De Lédinghen V. Impact of Preexisting Inflammatory Bowel Disease on the Outcome of Liver Transplantation for Primary Sclerosing Cholangitis. Liver Transpl 2020; 26:1477-1491. [PMID: 32603007 DOI: 10.1002/lt.25838] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 05/21/2020] [Accepted: 05/30/2020] [Indexed: 02/07/2023]
Abstract
Approximately 80% of patients with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD), and its effect on the outcomes of liver transplantation (LT) for PSC is unclear. We retrospectively collected data from adults who underwent LT for PSC from 1989 to January 2018 in 4 French LT centers. We compared the rates of patient and graft survivals and of complications after LT. Among 87 patients, 52 (60%) had preexisting IBD. Excluding those who died within the first 3 months, the 10-year patient survival and graft survival rates were 92.6% (95% confidence interval [CI], 84.3%-100%) and 77.1% (53.8%-85.3%), respectively, in the PSC with IBD (PSC-IBD) group and 97.1% (91.4%-100%; P = 0.44) and 83.2% (69.6%-96.9%; P = 0.43) in the isolated PSC group, respectively. Exposure to azathioprine after LT was significantly associated with mortality (odds ratio [OR], 15.55; 1.31-184.0; P = 0.03), whereas exposure to mycophenolate mofetil was associated with improved survival (OR, 0.17; 95% CI, 0.04-0.82; P = 0.03), possibly an era effect. The rate of recurrent PSC was 21% in the PSC-IBD group and 11% in the isolated PSC group (P = 0.24). Severe infections occurred in 125 per 1000 person-years in both groups. Exposure to mycophenolate mofetil was associated with a lower risk of infection (OR, 0.26; 95% CI, 0.08-0.85; P = 0.03). The presence of IBD was associated with cytomegalovirus (CMV) infection (OR, 3.24; 95% CI, 1.05-9.98; P = 0.04). IBD prior to LT for PSC may not affect patient or transplant survival but may increase the risk of CMV infection.
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Affiliation(s)
- Marie Irlès-Depé
- Service d'Hépatologie, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
| | - Stéphanie Roullet
- Service de Chirurgie Hépatobiliaire, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
| | - Martine Neau-Cransac
- Service de Chirurgie Hépatobiliaire, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
| | - Jérôme Dumortier
- Service de Gastro-Entérologie, Hôpital Haut-Lévêque, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
| | - Sébastien Dharancy
- Service d'Anesthésie-Réanimation Uro-Vasculaire et Transplantation Rénale, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
| | - Pauline Houssel-Debry
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Olivier Boillot
- Service de Gastro-Entérologie, Hôpital Haut-Lévêque, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
| | - Laurence Chiche
- Service d'Hépatologie, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France
| | - Christophe Laurent
- Service d'Hépatologie, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France
| | - David Laharie
- Service d'Hépatologie, Hôpital Pont-Chaillou, Centre Hospitalier Universitaire de Rennes, Rennes, France
| | - Victor De Lédinghen
- Service d'Hépatologie, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
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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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Chen C, Ke R, Yang F, Cai Q, Liu J, Huang X, Chen J, Xu F, Jiang Y. Risk factors for recurrent autoimmune liver diseases after liver transplantation: A meta-analysis. Medicine (Baltimore) 2020; 99:e20205. [PMID: 32443344 PMCID: PMC7253929 DOI: 10.1097/md.0000000000020205] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 04/04/2020] [Accepted: 04/09/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Autoimmune liver disease (ALD) is a chronic liver disease caused by immune dysfunction in the body. However, no causative or curative medical treatment with proven efficacy exists to cure ALDs, and liver transplantation (LT) remains the only effective treatment available. However, the problem of recurrence of ALDs (rALDs) still remains after LT, which seriously affects the survival rate of the patients. Therefore, clinicians need to be aware of the risk factors affecting rALDs after LT. Therefore, this meta-analysis aims to define the risk factors for rALDs, which include the recurrence of primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. METHODS A systematic search in Pubmed, Embase, Cochrane library and Web of Science databases was performed from 1980 to 2019. The inclusion criteria were risk factors for developing rALDs after LT. However, case series, case reports, reviews, meta-analysis and studies only including human immunodeficiency virus cases, children, and pregnant patients were excluded. RESULTS The electronic database search yielded 1728 results. Sixty-three retrospective cohort studies met the inclusion criteria and 13 were included in the meta-analysis. The final cohort included 5077 patients, and among them, 21.96% developed rALDs. Colectomy before LT, HR 0.59 (95% confidence interval [CI]: 0.37-0.96), cholangiocarcinoma, HR 3.42 (95% CI: 1.88-6.21), multiple episodes of acute cellular rejection, HR 2.07 (95% CI: 1.27-3.37), model for end-stage liver disease score, HR 1.05 (95% CI: 1.02-1.08), use of mycophenolate mofetil, HR 1.46 (95% CI: 1.00-2.12) and the use of cyclosporin A, HR 0.69 (95% CI: 0.49-0.97) were associated with the risk of rprimary sclerosing cholangitis. In addition, the use of tacrolimus, HR 1.73 (95% CI: 1.00-2.99) and cyclosporin A, HR 0.59 (95% CI: 0.39-0.88) were associated with the risk of rALD. CONCLUSIONS Multiple risk factors for rALDs were identified, such as colectomy before LT, cholangiocacinoma, multiple episodes of acute cellular rejection, model for end-stage liver disease score, and especially the use of mycophenolate mofetil, cyclosporin A and tacrolimus.
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Affiliation(s)
- Chongfa Chen
- Department of Hepatobiliary Surgery, Dongfang Hospital, Xiamen University
| | - Ruisheng Ke
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xiamen University
| | - Fang Yang
- Department of Hepatobiliary Surgery, 900 Hospital of the Joint Logistics Team, China
| | - Qiucheng Cai
- Department of Hepatobiliary Surgery, 900 Hospital of the Joint Logistics Team, China
| | - Jianyong Liu
- Department of Hepatobiliary Surgery, 900 Hospital of the Joint Logistics Team, China
| | - Xinghua Huang
- Department of Hepatobiliary Surgery, 900 Hospital of the Joint Logistics Team, China
| | - Jianwei Chen
- Department of Hepatobiliary Surgery, 900 Hospital of the Joint Logistics Team, China
| | - Fengfeng Xu
- Department of Hepatobiliary Surgery, Dongfang Hospital, Xiamen University
| | - Yi Jiang
- Department of Hepatobiliary Surgery, Dongfang Hospital, Xiamen University
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Choudhary NS, Saigal S, Thummala S, Saraf N, Rastogi A, Bhangui P, Srinivasan T, Yadav SK, Nundy S, Soin AS. Good Long-Term Outcomes in Patients With Primary Sclerosing Cholangitis Undergoing Living Donor Liver Transplantation. J Clin Exp Hepatol 2020; 10:442-447. [PMID: 33029052 PMCID: PMC7527842 DOI: 10.1016/j.jceh.2020.02.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 02/09/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a progressive cholestatic disorder with liver transplantation (LT) being the only definitive treatment in end-stage disease. Recurrence of PSC after LT is a significant concern which can lead to graft loss. The aim of this study is to find out the disease recurrence and long-term outcome after living donor liver transplantation (LDLT) in PSC. METHODS We conducted a retrospective review of all patients undergoing LDLT for PSC at our centre. Of 2268 adult LTs from August 2004 to July 2018, 32 (1.4%) patients underwent LDLT for PSC including 6 with PSC and autoimmune hepatitis overlap. The data were reviewed to look for PSC recurrence, complications, and overall survival. All patients received tacrolimus-based immunosuppression. Data are shown as number, percentage, median, and interquartile range (IQR). RESULT The mean age of 32 LDLT recipients was 44 ± 12 years (males 22, females 10). At the time of transplantation, the mean child's score was 9 ± 1.6 and model for end-stage liver disease score was 18.9 ± 6.4. Ulcerative colitis was seen in 7 patients and none had cholangiocarcinoma. Majority of patients (n = 29) received right lobe graft and all but 3 underwent hepaticojejunostomy for biliary reconstruction. PSC recurrence was seen in 6 (20%) patients during a median follow-up of 59 (29-101) months, after exclusion of 2 patients with early mortality. A total of five patients died during follow-up, and one of these deaths was due to PSC recurrence. There were 2 perioperative deaths due to sepsis and 3 deaths on follow-up (sepsis in 2 and PSC recurrence in 1). CONCLUSION LDLT can be performed in PSC with good overall long-term outcomes.
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Key Words
- BMI, body mass index
- CMV, cytomegalovirus
- CT, computed tomography
- DDLT, deceased donor liver transplantation
- LAI, Liver attenuation index
- LDLT
- LDLT, living donor liver transplantation
- LT, liver transplantation
- MRCP, magnetic resonance cholangiopancreatography
- PSC, primary sclerosing cholangitis
- UC, ulcerative colitis
- outcome
- primary sclerosing cholangitis
- recurrence
- survival
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Affiliation(s)
- Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, Gurugram, Delhi (NCR), India
| | - Sanjiv Saigal
- Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, Gurugram, Delhi (NCR), India,Address for correspondence. Dr Sanjiv Saigal MD, DM, MRCP Director Hepatology and Liver Transplantation, Institute of liver transplantation and regenerative medicine, Medanta The Medicity, sector 38, Gurgaon, PIN 122001, Haryana, India
| | - Srikanth Thummala
- Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, Gurugram, Delhi (NCR), India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, Gurugram, Delhi (NCR), India
| | - Amit Rastogi
- Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, Gurugram, Delhi (NCR), India
| | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, Gurugram, Delhi (NCR), India
| | - Thiagrajan Srinivasan
- Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, Gurugram, Delhi (NCR), India
| | - Sanjay K. Yadav
- Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, Gurugram, Delhi (NCR), India
| | | | - Arvinder S. Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, Gurugram, Delhi (NCR), India
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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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Zhang C, Hussaini T, Yoshida EM. Review of pharmacotherapeutic treatments for primary sclerosing cholangitis. CANADIAN LIVER JOURNAL 2019; 2:58-70. [PMID: 35990218 PMCID: PMC9202752 DOI: 10.3138/canlivj-2018-0016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 08/15/2018] [Indexed: 11/13/2023]
Abstract
BACKGROUND The objective of this review was to evaluate pharmacotherapeutic treatments for primary sclerosing cholangitis (PSC) through a literature search of current published data. A review of the current clinical data for each treatment is discussed. METHODS We conducted a systematic literature search for articles using EMBASE (1980 to April 1, 2018), and MEDLINE (1948 to April 1, 2018) using Ovid, to identify studies investigating various therapies in PSC. Search terms included the following: primary sclerosing cholangitis, cholangitis, sclerosing cholangitis; ursodeoxycholic acid, glucocorticoids, cyclosporine, tacrolimus, methotrexate, azathioprine, 6-mercaptopurine, penicillamine, anti-TNF, antibiotics, and probiotics. We also performed a review of current clinical trials using ClinicalTrials.gov. We considered for review relevant studies published in English, pilot studies, and randomized controlled trials involving human subjects. RESULTS Therapies that have been investigated in the management of PSC include those used in search terms and others that were not included in our search parameters. Analysis of published data involving each therapy was explored and none have shown any sustained, significant benefit in the treatment of PSC. In terms of relevance to patient care and clinical practice, this review evaluates and compares various pharmacotherapeutic treatments for PSC where liver transplantation remains the only definitive treatment. CONCLUSIONS To date, no clinical study of any drug has demonstrated effectiveness in terms of survival benefit or a decreased need for liver transplantation. More clinical studies are needed, and patients need to be adequately informed before any medical therapy for PSC is undertaken.
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Affiliation(s)
- Chaoran Zhang
- Internal Medicine Residency Training Program, Department of Medicine, University of British Columbia, Vancouver, British Columbia;
| | - Trana Hussaini
- Department of Pharmaceutical Sciences Medicine, Vancouver General Hospital, Vancouver, British Columbia;
| | - Eric M Yoshida
- Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia
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Abstract
Hepatobiliary disorders are commonly encountered in patients with inflammatory bowel disease (IBD). Although primary sclerosing cholangitis is the stereotypical hepatobiliary disorder associated with IBD, other diseases, including autoimmune hepatitis and nonalcoholic fatty liver disease, also are encountered in this population. Several agents used for treatment of IBD may cause drug-induced liver injury, although severe hepatotoxicity occurs infrequently. Furthermore, reactivation of hepatitis B virus infection may occur in patients with IBD treated with systemic corticosteroids and biologic agents.
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Affiliation(s)
- Mahmoud Mahfouz
- Department of Internal Medicine, Mount Sinai Medical Center, 4300 Alton Road, Suite 301, Miami Beach, FL 33140, USA
| | - Paul Martin
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, 1120 Northwest 14 Street #1115, Miami, FL 33136, USA.
| | - Andres F Carrion
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, 1120 Northwest 14 Street #1115, Miami, FL 33136, USA
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39
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Primary Sclerosing Cholangitis: A Concise Review of Diagnosis and Management. Dig Dis Sci 2019; 64:632-642. [PMID: 30725292 DOI: 10.1007/s10620-019-05484-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 01/19/2019] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterized by progressive idiopathic stricturing of the biliary system, typically leading to cirrhosis, end-stage liver disease, and colonic or hepatobiliary malignancy. Its presentation is often that of asymptomatic alkaline phosphatase elevation. When symptoms are present, they typically include fatigue, pruritus, or jaundice. The diagnosis can be confirmed via cholangiography, either magnetic resonance cholangiography (MRCP) or endoscopic retrograde cholangiography if the former is inconclusive. The clinical course is marked by progressive liver disease leading to cirrhosis with its attendant complications of portal hypertension, often including recurrent episodes of cholangitis. Greater elevation in alkaline phosphatase or liver stiffness is associated with worse clinical outcomes. Management includes endoscopic treatment of symptomatic biliary strictures and evaluation of dominant strictures as no adequate medical treatment is available. Multiple medical therapies are under evaluation. Ultimately, liver transplantation may be necessary for management of decompensated cirrhosis or disabling symptoms. There is also a markedly increased risk of cancer, notably including cholangiocarcinoma and gallbladder and colorectal cancers (particularly in patients with colitis). Cancer screening can be done with semi-annual liver imaging (MRCP or ultrasound) and colonoscopy every 1-2 years in those with colitis.
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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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Fousekis FS, Theopistos VI, Mitselos IV, Skamnelos A, Kavvadias A, Katsanos KH, Christodoulou DK. Specific Features of Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis. J Clin Med Res 2019; 11:81-88. [PMID: 30700999 PMCID: PMC6340671 DOI: 10.14740/jocmr3680] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 11/20/2018] [Indexed: 12/12/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic and progressive disease of the biliary tract. PSC is strongly associated with inflammatory bowel disease (IBD), mainly with ulcerative colitis, and most PSC patients have underlying IBD. The pathophysiological interactions between IBD and PSC are unclear, although it seems that the patients with IBD and PSC have a distinct phenotype. IBD with coexisting PSC is more extensive and is characterized by milder activity compared to IBD alone. The coexistence of PSC increases the risk for colorectal cancer in IBD patients and lifelong annual surveillance colonoscopy is recommended. Also, liver transplantation (LT) for PSC may affect the course of IBD. In addition, the management of IBD after LT includes many specific problems. On the other hand, the effect of IBD on the natural history of PSC appears to be milder. However, IBD may increase the risk of postsurgical complications after LT and is a risk factor for recurrent PSC after LT. Overall, the coexistence of IBD with PSC changes the management, natural history and prognosis of both diseases.
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Affiliation(s)
- Fotios S. Fousekis
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Vasileios I. Theopistos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Ioannis V. Mitselos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Alexandros Skamnelos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Athanasios Kavvadias
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Konstantinos H. Katsanos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Dimitrios K. Christodoulou
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
- Corresponding Author: Dimitrios K. Christodoulou, Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina 45100, Greece.
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Wadsworth CA, Dixon PH, Taylor-Robinson S, Kim JU, Zabron AA, Wong JH, Chapman MH, McKay SC, Spalding DR, Wasan HS, Pereira SP, Thomas HC, Whittaker JC, Williamson C, Khan SA. Polymorphisms in Natural Killer Cell Receptor Protein 2D (NKG2D) as a Risk Factor for Cholangiocarcinoma. J Clin Exp Hepatol 2019; 9:171-175. [PMID: 31024198 PMCID: PMC6477142 DOI: 10.1016/j.jceh.2018.06.521] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 06/24/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Understanding of the significant genetic risk factors for Cholangiocarcinoma (CC) remains limited. Polymorphisms in the natural killer cell receptor G2D (NKG2D) gene have been shown to increase risk of CC transformation in patients with Primary Sclerosing Cholangitis (PSC). We present a validation study of NKG2D polymorphisms in CC patients without PSC. METHODS Seven common Single Nucleotide Polymorphisms (SNPs) of the NKG2D gene were genotyped in 164 non-PSC related CC subjects and 257 controls with HaploView. The two SNPs that were positively identified in the previous Scandinavian study, rs11053781 and rs2617167, were included. RESULTS The seven genotyped SNPs were not associated with risk of CC. Furthermore, haplotype analysis revealed that there was no evidence to suggest that any haplotype differs in frequency between cases and controls (P > 0.1). CONCLUSION The common genetic variation in NKG2D does not correlate significantly with sporadic CC risk. This is in contrast to the previous positive findings in the Scandinavian study with PSC-patients. The failure to reproduce the association may reflect an important difference between the pathogenesis of sporadic CC and that of PSC-related CC. Given that genetic susceptibility is likely to be multifaceted and complex, further validation studies that include both sporadic and PSC-related CC are required.
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Affiliation(s)
- Christopher A. Wadsworth
- Digestive Health Section, Department of Surgery and Cancer, St Mary’s Hospital Campus, Imperial College London, London, United Kingdom
| | - Peter H. Dixon
- Department of Women and Children’s Health, School of Life Course Sciences, Guy’s Hospital Campus, King’s College London, London, United Kingdom
| | - Simon Taylor-Robinson
- Digestive Health Section, Department of Surgery and Cancer, St Mary’s Hospital Campus, Imperial College London, London, United Kingdom
| | - Jin U. Kim
- Digestive Health Section, Department of Surgery and Cancer, St Mary’s Hospital Campus, Imperial College London, London, United Kingdom
| | - Abigail A. Zabron
- Digestive Health Section, Department of Surgery and Cancer, St Mary’s Hospital Campus, Imperial College London, London, United Kingdom
| | - Jason H. Wong
- Digestive Health Section, Department of Surgery and Cancer, St Mary’s Hospital Campus, Imperial College London, London, United Kingdom
| | - Michael H. Chapman
- Institute for Liver & Digestive Health, Royal Free Hospital Campus, University College London, London, United Kingdom
| | - Siobhan C. McKay
- Surgery Section, Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College London, London, United Kingdom
| | - Duncan R. Spalding
- Surgery Section, Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College London, London, United Kingdom
| | - Harpreet S. Wasan
- Oncology Section, Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College London, London, United Kingdom
| | - Steve P. Pereira
- Institute for Liver & Digestive Health, Royal Free Hospital Campus, University College London, London, United Kingdom
| | - Howard C. Thomas
- Digestive Health Section, Department of Surgery and Cancer, St Mary’s Hospital Campus, Imperial College London, London, United Kingdom
| | - John C. Whittaker
- Statistical Platforms and Technologies, Medicines Research Centre, GlaxoSmithKline, Stevenage, Hertfordshire, United Kingdom,Statistical Genetics Unit, London School of Hygiene and Tropical Medicine, University of London, London, United Kingdom
| | - Catherine Williamson
- Department of Women and Children’s Health, School of Life Course Sciences, Guy’s Hospital Campus, King’s College London, London, United Kingdom
| | - Shahid A. Khan
- Digestive Health Section, Department of Surgery and Cancer, St Mary’s Hospital Campus, Imperial College London, London, United Kingdom,Address for correspondence: Shahid A. Khan, Liver Unit, 10th Floor QEQM Building, St Mary’s Campus, Imperial College London, Praed Street, London W2 1NY, United Kingdom. Tel: +44 0203 312 6454/6254; fax: +44 0207 724 9369.
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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: 9] [Impact Index Per Article: 1.3] [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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Staufer K, Kivaranovic D, Rasoul-Rockenschaub S, Soliman T, Trauner M, Berlakovich G. Waitlist mortality and post-transplant survival in patients with cholestatic liver disease - Impact of changes in allocation policy. HPB (Oxford) 2018; 20:916-924. [PMID: 29937419 DOI: 10.1016/j.hpb.2018.03.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 02/26/2018] [Accepted: 03/30/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study investigated the impact of Model of end-stage liver disease (MELD)-score introduction (MELDi) on waitlist mortality and post-liver transplant (LT) survival in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). METHODS LT candidates with PSC or PBC listed between January 1983 and March 2016 were included and followed until December 2016. After MELDi in 2004, PBC patients were listed according to labMELD, PSC patients according to the highest MELD during active cholangitis (chMELD). RESULTS In total, 100 PBC and 76 PSC patients were included. Waitlist mortality in PBC was significantly higher than in PSC (16% vs. 5.3%, p = 0.031), whereas PSC patients were significantly more often withdrawn from the waitlist due to improved condition (3.0% vs. 13.2%, p = 0.017). Competing risks analysis identified MELDi (HR = 4.12) and PBC (HR = 2.95) as significant predictors of waitlist mortality. Yet, overall 10 y-patient survival increased after MELDi by 18.8% leading to a 1 y-, 5 y-, and 10 y-patient survival of 98.2%, 70.6% and 70.6% in PBC, and 83.3%, 83.3%, and 80.6% in PSC, respectively. CONCLUSIONS PSC patients showed significantly lower waitlist mortality irrespective of MELDi, whereas in PBC waitlist mortality further increased after MELDi. Utility of MELD and chMELD did not impair post LT outcome.
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Affiliation(s)
- Katharina Staufer
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Austria.
| | - Danijel Kivaranovic
- Department of Statistics and Operations Research, University of Vienna, Vienna, Austria
| | | | - Thomas Soliman
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria
| | - Gabriela Berlakovich
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Austria
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Palmela C, Peerani F, Castaneda D, Torres J, Itzkowitz SH. Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Review of the Phenotype and Associated Specific Features. Gut Liver 2018; 12:17-29. [PMID: 28376583 PMCID: PMC5753680 DOI: 10.5009/gnl16510] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 12/19/2016] [Accepted: 01/05/2017] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disease that is associated with inflammatory bowel disease (IBD) in approximately 70% of cases. Although the pathogenesis is still unknown for both diseases, there is increasing evidence to indicate that they share a common underlying predisposition. Herein, we review the epidemiology, diagnosis, disease pathogenesis, and specific clinical features of the PSC-IBD phenotype. Patients with PSC-IBD have a distinct IBD phenotype with an increased incidence of pancolitis, backwash ileitis, and rectal sparing. Despite often having extensive colonic involvement, these patients present with mild intestinal symptoms or are even asymptomatic, which can delay the diagnosis of IBD. Although the IBD phenotype has been well characterized in PSC patients, the natural history and disease behavior of PSC in PSC-IBD patients is less well defined. There is conflicting evidence regarding the course of IBD in PSC-IBD patients who receive liver transplantation and their risk of recurrent PSC. IBD may also be associated with an increased risk of cholangiocarcinoma in PSC patients. Overall, the PSC-IBD population has an increased risk of developing colorectal neoplasia compared to the conventional IBD population. Lifelong annual surveillance colonoscopy is currently recommended.
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Affiliation(s)
- Carolina Palmela
- Division of Gastroenterology, Surgical Department, Hospital Beatriz Ângelo, Loures, Portugal
| | - Farhad Peerani
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Daniel Castaneda
- Division of Internal Medicine, Mount Sinai St. Luke's and Mount Sinai West Hospitals, New York, NY, USA
| | - Joana Torres
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Steven H Itzkowitz
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Buchholz BM, Lykoudis PM, Ravikumar R, Pollok JM, Fusai GK. Role of colectomy in preventing recurrent primary sclerosing cholangitis in liver transplant recipients. World J Gastroenterol 2018; 24:3171-3180. [PMID: 30065563 PMCID: PMC6064960 DOI: 10.3748/wjg.v24.i28.3171] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 07/08/2018] [Accepted: 07/16/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To study the published evidence on the impact of colectomy in preventing recurrent primary sclerosing cholangitis (rPSC).
METHODS An unrestricted systematic literature search in PubMed, EMBASE, Medline OvidSP, ISI Web of Science, Lista (EBSCO) and the Cochrane library was performed on clinical studies investigating colectomy in liver transplantation (LT) recipients with and without rPSC in the liver allograft. Study quality was evaluated according to a modification of the methodological index for non-randomized studies (MINORS) criteria. Primary endpoints were the impact of presence, timing and type of colectomy on rPSC. Overall presence of inflammatory bowel disease (IBD), time of IBD diagnosis, posttransplant IBD and immunosuppressive regimen were investigated as secondary outcome.
RESULTS The literature search yielded a total of 180 publications. No randomized controlled trial was identified. Six retrospective studies met the inclusion criteria of which 5 studies were graded as high quality articles. Reporting of IBD was heterogenous but in four publications, either inflammatory bowel disease, ulcerative colitis or in particular active colitis post-LT significantly increased the risk of rPSC. The presence of an intact (i.e., retained) colon at LT was identified as risk factor for rPSC in two of the high quality studies while four studies found no effect. Type of colectomy was not associated with rPSC but this endpoint was underreported (only in 33% of included studies). Neither tacrolimus nor cyclosporine A yielded a significant benefit in disease recurrence of primary sclerosing cholangitis (PSC).
CONCLUSION The data favours a protective role of pre-/peri-LT colectomy in rPSC but the current evidence is not strong enough to recommend routine colectomy for rPSC prevention.
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Affiliation(s)
- Bettina M Buchholz
- Department of HPB Surgery and Liver Transplantation, Royal Free Hospital London, London NW32QG, United Kingdom
| | - Panagis M Lykoudis
- Department of HPB Surgery and Liver Transplantation, Royal Free Hospital London, London NW32QG, United Kingdom
| | - Reena Ravikumar
- Department of HPB Surgery and Liver Transplantation, Royal Free Hospital London, London NW32QG, United Kingdom
| | - Joerg M Pollok
- Department of HPB Surgery and Liver Transplantation, Royal Free Hospital London, London NW32QG, United Kingdom
| | - Giuseppe K Fusai
- Department of HPB Surgery and Liver Transplantation, Royal Free Hospital London, London NW32QG, United Kingdom
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De Novo Autoimmune Hepatitis Following Liver Transplantation. Transplant Proc 2018; 50:1451-1456. [DOI: 10.1016/j.transproceed.2018.02.066] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Revised: 02/01/2018] [Accepted: 02/17/2018] [Indexed: 02/07/2023]
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Fousekis FS, Theopistos VI, Katsanos KH, Tsianos EV, Christodoulou DK. Hepatobiliary Manifestations and Complications in Inflammatory Bowel Disease: A Review. Gastroenterology Res 2018; 11:83-94. [PMID: 29707074 PMCID: PMC5916631 DOI: 10.14740/gr990w] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2018] [Accepted: 03/12/2018] [Indexed: 12/12/2022] Open
Abstract
Liver and biliary track diseases are common extraintestinal manifestations of inflammatory bowel disease (IBD), reported both in Crohn’s disease and ulcerative colitis, and may occur at any time during the natural course of the disease. Their etiology is mainly related to pathophysiological changes induced by IBD, and secondary, due to drugs used in IBD. Fatty liver is considered as the most frequent hepatobiliary manifestation in IBD, while primary sclerosing cholangitis (PSC) is the most correlated hepatobiliary disorder and is more prevalent in patients with ulcerative colitis. PSC can cause serious complications from the liver, biliary tree, and gallbladder and can lead to liver failure. Less frequently, IBD-associated hepatobiliary manifestations include cholelithiasis, granulomatous hepatitis, portal vein thrombosis, IgG4-related cholangiopathy, pyogenic liver abscess, hepatic amyloidosis and primary biliary cirrhosis. Most of the drugs used for IBD treatment may cause liver toxicity. Methotrexate and thiopurines carry the higher risk for hepatotoxicity, and in many cases, dose adjustment may normalize the liver biochemical tests. Reactivation of hepatitis B and C virus during immunosuppressive use, especially during use of biological agents, is a major concern, and adequate screening, vaccination and prophylactic treatment is warranted.
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Affiliation(s)
- Fotios S Fousekis
- Department of Gastroenterology and Hepatology, Medical School of Ioannina, Greece
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Zhong CP, Xi ZF, Xia Q. Clinical analysis of liver transplantation in autoimmune liver diseases. Hepatobiliary Pancreat Dis Int 2018; 17:27-31. [PMID: 29428100 DOI: 10.1016/j.hbpd.2018.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Accepted: 09/25/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND Autoimmune liver diseases (ALDs) consist of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), IgG4-associated cholangitis and overlap syndromes. Patients with these diseases may gradually progress to end-stage liver diseases and need liver transplantation. The present study aimed to explore the prognosis of patients with ALDs after liver transplantation. METHODS The clinical data of 80 patients with ALD (24 cases of AIH, 35 of PBC, 15 of PSC and 6 of AIH-PBC overlap syndromes) who underwent liver transplantation in Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2004 to September 2016 were collected retrospectively. The causes of death were analyzed and the postoperative cumulative survival rate was estimated by the Kaplan-Meier method. Recurrence and other complications were also analyzed. RESULTS Of the 80 patients, 18 were males and 62 were females. The average age was 50.5 years and the average Model for End-stage Liver Disease (MELD) score was 14.1. After a median follow-up of 19.8 months, 8 patients died. The 1-, 3- and 5-year cumulative survival rates were all 89.0%. Three cases of recurrent ALDs were diagnosed (3.8%) but they were not totally consistent with primary diseases. Biliary tract complication occurred in 10 patients (12.5%). The new onset of tumor was observed in 1 patient (1.3%). De novo HBV/CMV/EBV infection was found in 3, 8 and 3 patients, respectively. CONCLUSION Liver transplantation is an effective and safe treatment for end-stage ALD.
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Affiliation(s)
- Cheng-Peng Zhong
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Zhi-Feng Xi
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Qiang Xia
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
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50
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Senter-Zapata M, Khan AS, Subramanian T, Vachharajani N, Dageforde LA, Wellen JR, Shenoy S, Majella Doyle MB, Chapman WC. Patient and Graft Survival: Biliary Complications after Liver Transplantation. J Am Coll Surg 2018; 226:484-494. [PMID: 29360615 DOI: 10.1016/j.jamcollsurg.2017.12.039] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 12/19/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Biliary complications (BCs) affect up to to 34% of liver transplant recipients and are a major source of morbidity and cost. This is a 13-year review of BCs after liver transplantation (LT) at a tertiary care center. STUDY DESIGN We conducted a single-center retrospective review of our prospective database to assess BCs in adult (aged 18 years or older) liver transplant recipients during a 13-year period (2002 to 2014). Biliary complications were divided into 3 subgroups: leak alone (L), stricture alone (S), and both leak and strictures (LS). Controls (no BCs) were used for comparison. RESULTS There were 1,041 adult LTs performed during the study period; BCs developed in 239 (23%) of these patients: 55 (23%) L, 148 (62%) S, and 36 (15%) LS. One hundred and two (43%) were early (less than 30 d). Surgical revision was required in 42 cases (17%) (30 L, 10 LS, and 2 S), while the remaining 197 (83%) were managed nonsurgically (25 L, 26 LS, and 146 S), with a mean of 4.2 interventions/patient. One-, 3-, and 5-year overall patient and graft survival was significantly reduced in patients with bile leaks (84%, 71%, and 68% and 76%, 67%, and 64%, respectively) compared with controls (90%, 84%, and 78% and 88%, 81%, and 76%, respectively [p < 0.05]). Patients with BCs had higher incidence of cholestatic liver disease, higher pre-LT bilirubin, higher use of T-tubes, higher use of donor after cardiac death grafts, and higher rates of acute rejection (p < 0.05). Patients with BCs had longer ICU and hospital stays and higher rates of 30- and 90-day readmissions (p < 0.01). Multivariate analysis identified cholestatic liver disease, Roux-en-Y anastomosis, donor risk index >2, and T-tubes as independent BC predictors. CONCLUSIONS Biliary complications after LT can significantly decrease patient and graft survival rates. Careful donor and recipient selection and attention to anastomotic technique can reduce BCs and improve outcomes.
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Affiliation(s)
- Michael Senter-Zapata
- Section of Transplant Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Adeel S Khan
- Section of Transplant Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Tanvi Subramanian
- Section of Transplant Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Neeta Vachharajani
- Section of Transplant Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Leigh Anne Dageforde
- Section of Transplant Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Jason R Wellen
- Section of Transplant Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Surendra Shenoy
- Section of Transplant Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Maria B Majella Doyle
- Section of Transplant Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - William C Chapman
- Section of Transplant Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO.
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