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Condon S, Levy C, Martin EF. Recurrent and De Novo Liver Disease After Liver Transplantation. Clin Liver Dis 2025; 29:313-335. [PMID: 40287274 DOI: 10.1016/j.cld.2024.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/29/2025]
Abstract
Disease recurrence after liver transplantation (LT) is common. Certain liver diseases such as autoimmune hepatitis and steatotic liver disease may appear de novo after LT. This review discusses post LT alcohol-associated liver disease, metabolic dysfunction-associated liver disease, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Both recurrent and de novo diseases are important causes of allograft failure.
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Affiliation(s)
- Sally Condon
- Transplant Hepatology/Gastroenterology, Swedish Organ Transplant Center, 1124 Columbia Street #600, Seattle, WA 98104, USA.
| | - Cynthia Levy
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1120 NW 14th Street, Miami, FL 33136, USA
| | - Eric F Martin
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1801 NW 9th Avenue, 7th Floor, Miami, FL 33136, USA
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2
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Smith MK, Montano-Loza AJ. Natural history and long-term management of autoimmune hepatitis. Expert Rev Gastroenterol Hepatol 2025:1-12. [PMID: 40205325 DOI: 10.1080/17474124.2025.2491531] [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: 01/16/2025] [Revised: 03/26/2025] [Accepted: 04/07/2025] [Indexed: 04/11/2025]
Abstract
INTRODUCTION Autoimmune hepatitis (AIH) is a relatively infrequent and complex liver disease characterized by acute or chronic inflammation, interface hepatitis in histology examination, elevation of immunoglobulin G (IgG), production of autoantibodies, and is often responsive to immunosuppression. The incidence of AIH has been increasing worldwide, affecting people of all ages and sexes. AIH represents a diagnostic challenge because of its heterogeneous presentation and the lack of pathognomonic findings. Even when treated, AIH can remain a progressive disease. In this review, we present recent data on the natural history of AIH and the developing evidence on the management of patients with AIH. AREAS COVERED This review outlines the clinical presentation, risk factors linked to poorer clinical outcomes, the diagnostic algorithm, and the current management strategies for individuals living with AIH. EXPERT OPINION AIH remains a clinical challenge, and new tools for better diagnosis and stratification of risk are needed. In addition, better treatments are needed as a complete response is achieved in less than 60% of cases, and intolerance to first-line treatment is frequent. The use of biological treatment in AIH seems to improve the response rate and minimize the risk of side effects of current medication in this increasingly prevalent disease.
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Affiliation(s)
- Matthew K Smith
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada
| | - Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada
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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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Mehtani R, Rathi S. Recurrence of Primary Disease After Adult Liver Transplant - Risk Factors, Early Diagnosis, Management, and Prevention. J Clin Exp Hepatol 2024; 14:101432. [PMID: 38975605 PMCID: PMC11222954 DOI: 10.1016/j.jceh.2024.101432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 04/14/2024] [Indexed: 07/09/2024] Open
Abstract
Liver transplantation offers a new lease of life to patients with end-stage liver disease and hepatocellular carcinoma. However, the implantation of an exogenous allograft and the accompanying immunosuppression bring their own challenges. Moreover, the persistence of risk factors for the initial liver insult place the new graft at a higher risk of damage. With the increasing number of liver transplants along with the improvement in survival posttransplant, the recurrence of primary disease in liver grafts has become more common. Pre-2015, the most common disease to recur after transplant was hepatitis C. However, directly acting antivirals have nearly eliminated this problem. The greatest challenge of disease recurrence we now face are those of nonalcoholic steatohepatitis, alcohol-related liver disease, and primary sclerosing cholangitis. We focus on the epidemiology and pathophysiology of the recurrence of primary disease after transplant. We also discuss means of early identification, risk stratification, prevention, and management of recurrent primary disease after liver transplantation.
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Affiliation(s)
- Rohit Mehtani
- Department of Hepatology, Amrita Institute of Medical Sciences and Research, Faridabad, Haryana, India
| | - Sahaj Rathi
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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5
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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6
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Chouik Y, Corpechot C, Francoz C, De Martin E, Guillaud O, Abergel A, Altieri M, Barbier L, Besch C, Chazouillères O, Conti F, Dharancy S, Durand F, Duvoux C, Gugenheim J, Hardwigsen J, Hilleret MN, Houssel-Debry P, Kamar N, Minello A, Neau-Cransac M, Pageaux GP, Radenne S, Roux O, Saliba F, Samuel D, Vanlemmens C, Woehl-Jaegle ML, Leroy V, Duclos-Vallée JC, Dumortier J. Autoimmune hepatitis recurrence after liver transplantation: "Les jeux sont faits". Liver Transpl 2024; 30:395-411. [PMID: 37788303 DOI: 10.1097/lvt.0000000000000278] [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: 04/10/2023] [Accepted: 08/30/2023] [Indexed: 10/05/2023]
Abstract
Autoimmune hepatitis (AIH) may recur after liver transplantation (LT). The aims of this study were to evaluate the incidence and risk factors for recurrent autoimmune hepatitis (rAIH). A multicenter retrospective French nationwide study, including all patients aged ≥16 transplanted for AIH, with at least 1 liver biopsy 1 year after LT, was conducted between 1985 and 2018. Risk factors for rAIH were identified using a multivariate Cox regression model. Three hundred and forty-four patients were included (78.8% women) with a median age at LT of 43.6 years. Seventy-six patients (22.1%) developed recurrence in a median time of 53.6 months (IQR, 14.1-93.2). Actuarial risk for developing rAIH was 41.3% 20 years after LT. In multivariate analysis, the strongest risk factor for rAIH was cytomegalovirus D+/R- mismatch status (HR=2.0; 95% CI: 1.1-3.6; p =0.03), followed by associated autoimmune condition. Twenty-one patients (27.6% of rAIH patients) developed liver graft cirrhosis after rAIH. Independent risk factors for these severe forms of rAIH were young age at LT, IgG levels >20.7 g/L, and LT in the context of (sub)fulminant hepatitis. Immunosuppression, especially long-term maintenance of corticosteroid therapy, was not significantly associated with rAIH. Recurrence of AIH after LT is frequent and may lead to graft loss. Recurrence is more frequent in young patients with active disease at the time of LT, yet systematic corticosteroid therapy does not prevent it.
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Affiliation(s)
- Yasmina Chouik
- Hospices civils de Lyon, Hôpital Edouard Herriot, Service d'Hépato-Gastroentérologie, and Université Claude Bernard Lyon 1, Lyon, France
- Hospices civils de Lyon, Hôpital de la Croix Rousse, Service d'Hépato-Gastroentérologie, Lyon, France
| | - Christophe Corpechot
- Hôpital Saint-Antoine, Centre de référence des maladies inflammatoires des voies biliaires et des hépatites auto-immunes, Filière de santé FILFOIE, Assistance Publique - Hôpitaux de Paris (AP-HP), INSERM UMRS 938, Centre de Recherche Saint-Antoine, Sorbonne Université, Paris
| | - Claire Francoz
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy
| | - Eleonora De Martin
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif
| | - Olivier Guillaud
- Hospices civils de Lyon, Hôpital Edouard Herriot, Service d'Hépato-Gastroentérologie, and Université Claude Bernard Lyon 1, Lyon, France
| | - Armand Abergel
- CHU Estaing, Médecine digestive, Institut Pascal, UMR 6602 UCA CNRS SIGMA, Clermont-Ferrand
| | - Mario Altieri
- Hôpital Côte de Nacre, Service d'Hépato-Gastroentérologie, Nutrition et Oncologie Digestive, Caen
| | - Louise Barbier
- CHU Tours, Hôpital Trousseau Service de chirurgie digestive, oncologique et endocrinienne, Transplantation hépatique, Tours
| | - Camille Besch
- CHRU Hautepierre, Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Strasbourg
| | - Olivier Chazouillères
- Hôpital Saint-Antoine, Centre de référence des maladies inflammatoires des voies biliaires et des hépatites auto-immunes, Filière de santé FILFOIE, Assistance Publique - Hôpitaux de Paris (AP-HP), INSERM UMRS 938, Centre de Recherche Saint-Antoine, Sorbonne Université, Paris
| | - Filomena Conti
- Service de Chirurgie Digestive et Hépato-Biliaire, Transplantation Hépatique, AP-HP Hôpital Pitié Salpêtrière, Paris
| | | | - François Durand
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy
| | | | - Jean Gugenheim
- Hôpital universitaire de Nice, service de Chirurgie Digestive et de Transplantation Hépatique - Université de Nice-Sophia-Antipolis, Nice
| | - Jean Hardwigsen
- APHM, Hôpital La Timone, Service chirurgie générale et transplantation hépatique Marseille
| | - Marie-Noëlle Hilleret
- CHU Grenoble-Alpes, Service d'hépato-gastroentérologie- INSERM U1209-Université Grenoble-Alpes, La Tronche
| | - Pauline Houssel-Debry
- Hôpital Universitaire de Pontchaillou, Service d'Hépatologie et Transplantation hépatique, Rennes
| | - Nassim Kamar
- CHU Rangueil, Département de Néphrologie et Transplantation d'Organes, Toulouse
| | - Anne Minello
- CHU Dijon, Service d'Hépato-gastroentérologie et oncologie digestive, Inserm EPICAD LNC-UMR1231, Université de Bourgogne-Franche Comté, Dijon
| | - Martine Neau-Cransac
- CHU de Bordeaux, Hôpital Haut Lévêque, Service de Chirurgie hépatobiliaire et de transplantation hépatique, Bordeaux
| | | | - Sylvie Radenne
- Hospices civils de Lyon, Hôpital de la Croix Rousse, Service d'Hépato-Gastroentérologie, Lyon, France
| | - Olivier Roux
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy
| | - Faouzi Saliba
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif
| | - Claire Vanlemmens
- Hôpital Jean Minjoz, Service d'Hépatologie et Soins Intensifs Digestifs, Besançon, France
| | - Marie-Lorraine Woehl-Jaegle
- CHU Tours, Hôpital Trousseau Service de chirurgie digestive, oncologique et endocrinienne, Transplantation hépatique, Tours
| | - Vincent Leroy
- CHU Grenoble-Alpes, Service d'hépato-gastroentérologie- INSERM U1209-Université Grenoble-Alpes, La Tronche
| | - Jean-Charles Duclos-Vallée
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif
| | - Jérôme Dumortier
- Hospices civils de Lyon, Hôpital Edouard Herriot, Service d'Hépato-Gastroentérologie, and Université Claude Bernard Lyon 1, Lyon, France
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7
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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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8
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Cooper KM, Delk M, Devuni D, Sarkar M. Sex differences in chronic liver disease and benign liver lesions. JHEP Rep 2023; 5:100870. [PMID: 37791378 PMCID: PMC10542645 DOI: 10.1016/j.jhepr.2023.100870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 06/23/2023] [Accepted: 07/01/2023] [Indexed: 10/05/2023] Open
Abstract
The epidemiology, natural history, and therapeutic responses of chronic liver diseases and liver lesions often vary by sex. In this review, we summarize available clinical and translational data on these aspects of the most common liver conditions encountered in clinical practice, including the potential contributions of sex hormones to the underlying pathophysiology of observed differences. We also highlight areas of notable knowledge gaps and discuss sex disparities in access to liver transplant and potential strategies to address these barriers. Given established sex differences in immune response, drug metabolism, and response to liver-related therapies, emerging clinical trials and epidemiological studies should prioritize dedicated analyses by sex to inform sex-specific approaches to liver-related care.
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Affiliation(s)
- Katherine M. Cooper
- UMass Chan Medical School, Department of Medicine, Division of Gastroenterology/Hepatology, Worcester, MA, United States
| | - Molly Delk
- University of California San Francisco, Department of Medicine, Division of Gastroenterology/Hepatology, San Francisco, CA, United States
| | - Deepika Devuni
- UMass Chan Medical School, Department of Medicine, Division of Gastroenterology/Hepatology, Worcester, MA, United States
| | - Monika Sarkar
- University of California San Francisco, Department of Medicine, Division of Gastroenterology/Hepatology, San Francisco, CA, United States
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9
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Berenguer M, de Martin E, Hessheimer AJ, Levitsky J, Maluf DG, Mas VR, Selzner N, Hernàndez-Èvole H, Lutu A, Wahid N, Zubair H. European Society for Organ Transplantation Consensus Statement on Biomarkers in Liver Transplantation. Transpl Int 2023; 36:11358. [PMID: 37711401 PMCID: PMC10498996 DOI: 10.3389/ti.2023.11358] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 07/25/2023] [Indexed: 09/16/2023]
Abstract
Currently, one-year survival following liver transplantation (LT) exceeds 90% in large international registries, and LT is considered definitive treatment for patients with end-stage liver disease and liver cancer. Recurrence of disease, including hepatocellular carcinoma (HCC), significantly hampers post-LT outcomes. An optimal approach to immunosuppression (IS), including safe weaning, may benefit patients by mitigating the effect on recurrent diseases, as well as reducing adverse events associated with over-/under-IS, including chronic kidney disease (CKD). Prediction of these outcome measures-disease recurrence, CKD, and immune status-has long been based on relatively inaccurate clinical models. To address the utility of new biomarkers in predicting these outcomes in the post-LT setting, the European Society of Organ Transplantation (ESOT) and International Liver Transplant Society (ILTS) convened a working group of experts to review literature pertaining to primary disease recurrence, development of CKD, and safe weaning of IS. Summaries of evidence were presented to the group of panelists and juries to develop guidelines, which were discussed and voted in-person at the Consensus Conference in Prague November 2022. The consensus findings and recommendations of the Liver Working Group on new biomarkers in LT, clinical applicability, and future needs are presented in this article.
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Affiliation(s)
- Marina Berenguer
- Hepatology and Liver Transplantation Unit, Hospital Universitario la Fe - IIS La Fe Valencia, CiberEHD and University of Valencia, Valencia, Spain
| | - Eleonora de Martin
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris-Saclay, Villejuif, France
| | - Amelia J. Hessheimer
- General & Digestive Surgery, Hospital Universitario La Paz, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Josh Levitsky
- Division of Gastroenterology and Hepatology, Department of Medicine, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Daniel G. Maluf
- Program in Transplantation, Department of Surgery, University of Maryland Medical Center, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Valeria R. Mas
- Surgical Sciences Research in Transplantation, Chief Surgical Sciences Division, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Nazia Selzner
- Ajmera Transplant Center, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | | | - Alina Lutu
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris-Saclay, Villejuif, France
| | - Nabeel Wahid
- Division of Gastroenterology and Hepatology, Department of Medicine, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Haseeb Zubair
- Surgical Sciences Division, University of Maryland School of Medicine, Baltimore, MD, United States
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10
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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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11
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Chouik Y, Chazouillères O, Francoz C, De Martin E, Guillaud O, Abergel A, Altieri M, Barbier L, Besch C, Conti F, Corpechot C, Dharancy S, Durand F, Duvoux C, Gugenheim J, Hardwigsen J, Hilleret MN, Houssel-Debry P, Kamar N, Maucort-Boulch D, Minello A, Neau-Cransac M, Pageaux GP, Radenne S, Roux O, Saliba F, Serée O, Samuel D, Vanlemmens C, Woehl-Jaegle ML, Leroy V, Duclos-Vallée JC, Dumortier J. Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years. Liver Int 2023; 43:1068-1079. [PMID: 36825353 DOI: 10.1111/liv.15552] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 02/14/2023] [Accepted: 02/20/2023] [Indexed: 02/25/2023]
Abstract
BACKGROUND & AIMS Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH). METHODS A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6 months) were excluded. RESULTS The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4-53.8). Median follow-up was 87.0 months (IQR, 43.5-168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR = 2.9; 95% CI, 1.4-6.2; p = 0.005) and occurrence of an infectious episode within the first year after LT (HR = 2.5; 95% CI, 1.2-5.1; p = 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR = 2.7; 95% CI, 1.5-5.0; p = 0.001), chronic rejection (HR = 2.9; 95% CI, 1.4-6.1; p = 0.005), biliary (HR = 2.0; 95% CI, 1.2-3.4; p = 0.009), vascular (HR = 1.8; 95% CI, 1.0-3.1; p = 0.044) and early septic (HR = 2.1; 95% CI, 1.2-3.5; p = 0.006) complications. CONCLUSION Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death.
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Affiliation(s)
- Yasmina Chouik
- Hospices civils de Lyon, Hôpital Edouard Herriot, et Université Claude Bernard Lyon 1, Lyon, France.,Hospices civils de Lyon, Hôpital de la Croix Rousse, Service d'Hépato-Gastroentérologie, Lyon, France
| | - Olivier Chazouillères
- AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie, INSERM UMR S 938, CDR Saint-Antoine, Centre de référence « Maladies inflammatoire des voies biliaires et hépatite auto-immune », Filière FILFOIE, Université Paris 6, UMR_S 938, CDR Saint-Antoine, Paris, France
| | - Claire Francoz
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy, France
| | - Eleonora De Martin
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France
| | - Olivier Guillaud
- Hospices civils de Lyon, Hôpital Edouard Herriot, et Université Claude Bernard Lyon 1, Lyon, France
| | - Armand Abergel
- CHU Estaing, Médecine Digestive, Institut Pascal, Clermont-Ferrand, France
| | - Mario Altieri
- Hôpital Côte de Nacre, Service d'Hépato-Gastroentérologie, Nutrition et Oncologie Digestive, Caen, France
| | - Louise Barbier
- CHU Tours, Hôpital Trousseau Service de chirurgie digestive, oncologique et endocrinienne, Transplantation hépatique, Tours, France
| | - Camille Besch
- CHRU Hautepierre, Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Strasbourg, France
| | - Filomena Conti
- Service de Chirurgie Digestive et Hépato-Biliaire, Transplantation Hépatique, AP-HP Hôpital Pitié Salpêtrière, Paris, France
| | - Christophe Corpechot
- AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie, INSERM UMR S 938, CDR Saint-Antoine, Centre de référence « Maladies inflammatoire des voies biliaires et hépatite auto-immune », Filière FILFOIE, Université Paris 6, UMR_S 938, CDR Saint-Antoine, Paris, France
| | | | - François Durand
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy, France
| | | | - Jean Gugenheim
- Hôpital universitaire de Nice, service de Chirurgie Digestive et de Transplantation Hépatique - Université de Nice-Sophia-Antipolis, Nice, France
| | - Jean Hardwigsen
- APHM, Hôpital La Timone, Service chirurgie générale et transplantation hépatique Marseille, Marseille, France
| | - Marie-Noëlle Hilleret
- CHU Grenoble-Alpes, Service d'hépato-gastroentérologie- INSERM U1209-Université Grenoble-Alpes, La Tronche, France
| | - Pauline Houssel-Debry
- Hôpital Universitaire de Pontchaillou, Service d'Hépatologie et Transplantation hépatique, Rennes, France
| | - Nassim Kamar
- CHU Rangueil, Département de Néphrologie et Transplantation d'Organes, Toulouse, France
| | - Delphine Maucort-Boulch
- Hospices Civils de Lyon, Service de Biostatistique et Bioinformatique & Université Lyon 1, Lyon, France
| | - Anne Minello
- CHU Dijon, Service d'Hépato-gastroentérologie et oncologie digestive, Inserm EPICAD LNC-UMR1231, Université de Bourgogne-Franche Comté, Dijon, France
| | - Martine Neau-Cransac
- CHU de Bordeaux, Hôpital Haut Lévêque, Service de Chirurgie hépatobiliaire et de transplantation hépatique, Bordeaux, France
| | | | - Sylvie Radenne
- Hospices civils de Lyon, Hôpital de la Croix Rousse, Service d'Hépato-Gastroentérologie, Lyon, France
| | - Olivier Roux
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy, France
| | - Faouzi Saliba
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France
| | - Olivier Serée
- Unité de Formation et de Recherche Santé Caen France, U1086 INSERM- "ANTICIPE", Caen, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France
| | - Claire Vanlemmens
- Hôpital Jean Minjoz, Service d'Hépatologie et Soins Intensifs Digestifs, Besançon, France
| | - Marie-Lorraine Woehl-Jaegle
- CHU Tours, Hôpital Trousseau Service de chirurgie digestive, oncologique et endocrinienne, Transplantation hépatique, Tours, France
| | - Vincent Leroy
- CHU Grenoble-Alpes, Service d'hépato-gastroentérologie- INSERM U1209-Université Grenoble-Alpes, La Tronche, France
| | - Jean-Charles Duclos-Vallée
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France
| | - Jérôme Dumortier
- Hospices civils de Lyon, Hôpital Edouard Herriot, et Université Claude Bernard Lyon 1, Lyon, France
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12
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Abstract
Abnormal liver tests are common after liver transplantation. The differential diagnosis depends on the clinical context, particularly the time course, pattern and degree of elevation, and donor and recipient factors. The perioperative period has distinct causes compared with months and years after transplant, including ischemia-reperfusion injury, vascular thrombosis, and primary graft nonfunction. Etiologies seen beyond the perioperative period include biliary complications, rejection, infection, recurrent disease, and non-transplant-specific causes. The evaluation begins with a liver ultrasound with Doppler as well as appropriate laboratory testing and culminates in a liver biopsy if the imaging and laboratory testing is unrevealing.
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Affiliation(s)
- Jacqueline B Henson
- Division of Gastroenterology, Department of Medicine, Duke University, DUMC Box 3913, Durham, NC 27710, USA. https://twitter.com/jackie_henson
| | - Andrew J Muir
- Division of Gastroenterology, Department of Medicine, Duke University, DUMC Box 3913, Durham, NC 27710, USA; Duke Clinical Research Institute, Duke University, DUMC Box 3913, Durham, NC 27710, USA.
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13
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Montano-Loza AJ, Ronca V, Ebadi M, Hansen BE, Hirschfield G, Elwir S, Alsaed M, Milkiewicz P, Janik MK, Marschall HU, Burza MA, Efe C, Calışkan AR, Harputluoglu M, Kabaçam G, Terrabuio D, de Quadros Onofrio F, Selzner N, Bonder A, Parés A, Llovet L, Akyıldız M, Arikan C, Manns MP, Taubert R, Weber AL, Schiano TD, Haydel B, Czubkowski P, Socha P, Ołdak N, Akamatsu N, Tanaka A, Levy C, Martin EF, Goel A, Sedki M, Jankowska I, Ikegami T, Rodriguez M, Sterneck M, Weiler-Normann C, Schramm C, Donato MF, Lohse A, Andrade RJ, Patwardhan VR, van Hoek B, Biewenga M, Kremer AE, Ueda Y, Deneau M, Pedersen M, Mayo MJ, Floreani A, Burra P, Secchi MF, Beretta-Piccoli BT, Sciveres M, Maggiore G, Jafri SM, Debray D, Girard M, Lacaille F, Lytvyak E, Mason AL, Heneghan M, Oo YH. Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation. J Hepatol 2022; 77:84-97. [PMID: 35143897 DOI: 10.1016/j.jhep.2022.01.022] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 01/26/2022] [Accepted: 01/27/2022] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival. METHODS We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis. RESULTS AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001). CONCLUSION Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH. LAY SUMMARY Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.
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Affiliation(s)
- Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada.
| | - Vincenzo Ronca
- Center for Liver Research & NIHR Birmingham BRC, University of Birmingham & University Hospital Birmingham NHS Foundation Trust, Institute of Immunology and Immunotherapy, University of Birmingham, UK
| | - Maryam Ebadi
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada
| | - Bettina E Hansen
- Toronto Center for Liver Disease, University Health Network, University of Toronto, Toronto, Canada
| | - Gideon Hirschfield
- Toronto Center for Liver Disease, University Health Network, University of Toronto, Toronto, Canada
| | - Saleh Elwir
- Baylor University Medical Center, Dallas, USA
| | | | - Piotr Milkiewicz
- Liver and Internal Medicine Unit, Medical University of Warsaw, Poland
| | - Maciej K Janik
- Liver and Internal Medicine Unit, Medical University of Warsaw, Poland
| | | | | | - Cumali Efe
- Department of Gastroenterology, Harran University Hospital, Şanlıurfa, Turkey
| | - Ali Rıza Calışkan
- Department of Gastroenterology, Inönü University School of Medicine, Malatya, Turkey
| | - Murat Harputluoglu
- Department of Gastroenterology, Inönü University School of Medicine, Malatya, Turkey
| | - Gökhan Kabaçam
- Clinic of Gastroenterology and Liver Transplantation, Guven Hospital Ankara, Turkey
| | - Débora Terrabuio
- Department of Gastroenterology - University of São Paulo School of Medicine, São Paulo, Brazil
| | | | - Nazia Selzner
- Toronto Center for Liver Disease, University Health Network, University of Toronto, Toronto, Canada
| | - Alan Bonder
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Albert Parés
- Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Laura Llovet
- Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Murat Akyıldız
- Koç University School of Medicine, Department of Gastroenterology and Liver Transplantation Center, Istanbul, Turkey
| | - Cigdem Arikan
- Koc University School of Medicine, Pediatric Gastroenterology and Hepatology, Organ Transplantation Center, Koc University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey
| | - Michael P Manns
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Department Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Richard Taubert
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Department Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Anna-Lena Weber
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Department Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Thomas D Schiano
- Recanati/Miller Transplantation Institute/Division of Liver Diseases, Mount Sinai Medical Center, New York, USA
| | - Brandy Haydel
- Recanati/Miller Transplantation Institute/Division of Liver Diseases, Mount Sinai Medical Center, New York, USA
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Piotr Socha
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Natalia Ołdak
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | | | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Cynthia Levy
- University of Miami Miller School of Medicine, Miami, USA
| | - Eric F Martin
- University of Miami Miller School of Medicine, Miami, USA
| | | | | | | | - Toru Ikegami
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | | | | | | | | | - Maria Francesca Donato
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Liver Tranplant Hepatology Unit, Division of Gastroenterology and Hepatology, Milan, Italy
| | | | - Raul J Andrade
- Gastroenterology Service -IBIMA. University Hospital and CIBERehd. University of Málaga, Spain
| | - Vilas R Patwardhan
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Bart van Hoek
- Leiden University Medical Center, Leiden, Netherlands
| | | | - Andreas E Kremer
- Department of Medicine, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Yoshihide Ueda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | | | - Mark Pedersen
- University of Texas Southwestern Medical Center, Dallas, USA
| | - Marlyn J Mayo
- University of Texas Southwestern Medical Center, Dallas, USA
| | - Annarosa Floreani
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | | | | | | | - Giuseppe Maggiore
- Hepatogastroenterology, Nutrition and Liver Transplant IRCCS Bambino Gesù Pediatric Hospital, Rome, Italy
| | | | - Dominique Debray
- Pediatric Liver Unit, French National Reference Center for Rare Diseases BA and Genetic Cholestasis, Hôpital Necker, Université de Paris, Paris, France
| | - Muriel Girard
- Pediatric Liver Unit, French National Reference Center for Rare Diseases BA and Genetic Cholestasis, Hôpital Necker, Université de Paris, Paris, France
| | - Florence Lacaille
- Gastroenterology-Hepatology-Nutrition Unit, Hôpital Necker-Enfants Malades, Paris, France
| | - Ellina Lytvyak
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada
| | - Andrew L Mason
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada
| | | | - Ye Htun 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, UK.
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14
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Fodor M, Zoller H, Oberhuber R, Sucher R, Seehofer D, Cillo U, Line PD, Tilg H, Schneeberger S. The Need to Update Endpoints and Outcome Analysis in the Rapidly Changing Field of Liver Transplantation. Transplantation 2022; 106:938-949. [PMID: 34753893 DOI: 10.1097/tp.0000000000003973] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Liver transplantation (LT) survival rates have continued to improve over the last decades, mostly due to the reduction of mortality early after transplantation. The advancement is facilitating a liberalization of access to LT, with more patients with higher risk profiles being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of high-risk donors. This is facilitated by novel technologies such as machine perfusion. Owing to these developments, reconsideration of the current and emerging endpoints for the assessment of the efficacy of existing and new therapies is warranted. While conventional early endpoints in LT have focused on the damage induced to the parenchyma, the fate of the bile duct and the recurrence of the underlying disease have a stronger impact on the long-term outcome. In light of this evolving landscape, we here attempt to reflect on the appropriateness of the currently used endpoints in the field of LT trials.
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Affiliation(s)
- Margot Fodor
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Heinz Zoller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Rupert Oberhuber
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Robert Sucher
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Clinic, Leipzig, Germany
| | - Daniel Seehofer
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Clinic, Leipzig, Germany
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplant Unit, Padua University Hospital, Padua, Italy
| | - Pal Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute for Clinical Medicine, University of Oslo, Oslo, Norway
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
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15
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Dumortier J, Besch C, Moga L, Coilly A, Conti F, Corpechot C, Del Bello A, Faitot F, Francoz C, Hilleret MN, Houssel-Debry P, Jezequel C, Lavayssière L, Neau-Cransac M, Erard-Poinsot D, de Lédinghen V, Bourlière M, Bureau C, Ganne-Carrié N. Non-invasive diagnosis and follow-up in liver transplantation. Clin Res Hepatol Gastroenterol 2022; 46:101774. [PMID: 34332131 DOI: 10.1016/j.clinre.2021.101774] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 07/23/2021] [Indexed: 02/04/2023]
Abstract
The field of liver transplantation directly or indirectly embodies all liver diseases, in addition to specific ones related to organ rejection (cellular and humoral). The recommended non-invasive methods for determining the indication for liver transplantation are the Model for End-stage Liver Disease score, and the alpha-foetoprotein score in case of hepatocellular carcinoma. Radiological methods are the cornerstones for the diagnosis of vascular and biliary complications after liver transplantation. The possible diseases of the liver graft after transplantation are multiple and often intertwined. Non-invasive diagnostic methods have been poorly evaluated in this context, apart from the recurrence of hepatitis C. Liver biopsy remains the gold standard for evaluating graft lesions in the majority of cases, especially graft rejection.
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Affiliation(s)
- Jérôme Dumortier
- Service d'hépato-gastroentérologie, Unité de transplantation hépatique, Hôpital Edouard Herriot - HCL, CHU Lyon, Lyon.
| | - Camille Besch
- Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Hôpital Hautepierre, CHRU Strasbourg, Strasbourg
| | - Lucile Moga
- Service d'Hépatologie et Transplantation Hépatique, Hôpital Beaujon, APHP, Clichy
| | - Audrey Coilly
- Centre Hépato-Biliaire, Hôpital Paul Brousse, APHP, Villejuif
| | - Filomena Conti
- Service d'Hépatologie et Transplantation Hépatique, Hôpital de la Pitié Salpétrière, APHP, Paris
| | | | - Arnaud Del Bello
- Département de néphrologie et transplantation d'organes, Hôpital Rangueil, CHU Toulouse, Toulouse
| | - François Faitot
- Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Hôpital Hautepierre, CHRU Strasbourg, Strasbourg
| | - Claire Francoz
- Service d'Hépatologie et Transplantation Hépatique, Hôpital Beaujon, APHP, Clichy
| | | | | | | | - Laurence Lavayssière
- Département de néphrologie et transplantation d'organes, Hôpital Rangueil, CHU Toulouse, Toulouse
| | | | - Domitille Erard-Poinsot
- Service d'hépato-gastroentérologie, Unité de transplantation hépatique, Hôpital Edouard Herriot - HCL, CHU Lyon, Lyon
| | - Victor de Lédinghen
- Unité Transplantation Hépatique, Hôpital Haut-Lévêque, CHU Bordeaux, Bordeaux
| | - Marc Bourlière
- Service d'hépato-gastroentérologie, Hôpital Saint Joseph & INSERM UMR 1252 IRD SESSTIM Aix Marseille Université, Marseille
| | | | - Nathalie Ganne-Carrié
- Service d'hépatologie, Hôpital Avicenne, APHP, Université Sorbonne Paris Nord, Bobigny & INSERM UMR 1138, Centre de Recherche des Cordeliers, Université de Paris
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16
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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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17
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Montano-Loza AJ, Allegretti JR, Cheung A, Ebadi M, Jones D, Kerkar N, Levy C, Rizvi S, Vierling JM, Alvarez F, Bai W, Gilmour S, Gulamhusein A, Guttman O, Hansen BE, MacParland S, Mason A, Onofrio F, Santamaria P, Stueck A, Swain M, Vincent C, Ricciuto A, Hirschfield G. Single Topic Conference on Autoimmune Liver Disease from the Canadian Association for the Study of the Liver. CANADIAN LIVER JOURNAL 2021; 4:401-425. [PMID: 35989897 PMCID: PMC9235119 DOI: 10.3138/canlivj-2021-0006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 02/09/2021] [Indexed: 11/20/2022]
Abstract
Autoimmune liver disease (AILD) spans a spectrum of chronic disorders affecting the liver parenchyma and biliary system. Three main categories of AILD are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). This review condenses the presentation and discussions of the Single Topic Conference (STC) on AILD that was held in Ottawa, Ontario, in November 2019. We cover generalities regarding disease presentation and clinical diagnosis; mechanistic themes; treatment paradigms; clinical trials, including approaches and challenges to new therapies; and looking beyond traditional disease boundaries. Although these diseases are considered autoimmune, the etiology and role of environmental triggers are poorly understood. AILDs are progressive and chronic conditions that affect survival and quality of life. Advances have been made in PBC treatment because second-line treatments are now available (obeticholic acid, bezafibrate); however, a significant proportion still present suboptimal response. AIH treatment has remained unchanged for several decades, and data suggest that fewer than 50% of patients achieve a complete response and as many as 80% develop treatment-related side effects. B-cell depletion therapy to treat AIH is in an early stage of development and has shown promising results. An effective treatment for PSC is urgently needed. Liver transplant remains the best option for patients who develop decompensated cirrhosis or hepatocellular carcinoma within specific criteria, but recurrent AILD might occur. Continued efforts are warranted to develop networks for AILD aimed at assessing geo-epidemiological, clinical, and biochemical differences to capture the new treatment era in Canada.
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Affiliation(s)
- Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - Jessica R Allegretti
- Division of Gastroenterology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Angela Cheung
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | - Maryam Ebadi
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - David Jones
- Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Nanda Kerkar
- Division of Gastroenterology, Hepatology and Nutrition, Golisano Children’s Hospital at Strong, University of Rochester Medical Center, New York, USA
| | - Cynthia Levy
- Schiff Center for Liver Diseases, University of Miami, Miami, Florida, USA
| | - Sumera Rizvi
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | | | - Fernando Alvarez
- Department of Pediatrics, Hôpital Sainte-Justine, University of Montreal, Montreal, Quebec, Canada
| | - Wayne Bai
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - Susan Gilmour
- Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, Canada
| | - Aliya Gulamhusein
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Orlee Guttman
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
| | - Bettina E Hansen
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Sonya MacParland
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Andrew Mason
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - Fernanda Onofrio
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Pere Santamaria
- Department of Microbiology, Immunology & Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
| | - Ashley Stueck
- Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Mark Swain
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | - Catherine Vincent
- Department of Medicine, University of Montreal, Montreal, Quebec, Canada
| | - Amanda Ricciuto
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Gideon Hirschfield
- Toronto Centre for Liver Disease, University Health Network & Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
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18
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Trivedi PJ, Hirschfield GM. Recent advances in clinical practice: epidemiology of autoimmune liver diseases. Gut 2021; 70:1989-2003. [PMID: 34266966 DOI: 10.1136/gutjnl-2020-322362] [Citation(s) in RCA: 127] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 06/24/2021] [Indexed: 12/13/2022]
Abstract
Autoimmune liver diseases are chronic inflammatory hepatobiliary disorders that when classically defined encompass three distinctive clinical presentations; primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Meaningful changes in disease epidemiology are reported, with increasing incidence and prevalence of AIH and PSC in Europe, and rising prevalence of PBC across Europe, North America and the Asia-Pacific region. However, there appears to be very significant global variation with contemporary incidence rates of disease per 100 000 ranging from 0.84 to 2.75 for PBC, 0.1 to 4.39 for PSC and 0.4 to 2.39 for AIH. Prevalence corresponds, and per 100 000 estimates for PBC range from 1.91 to 40.2, for PSC between 0.78 and 31.7 and for AIH from 4.8 to 42.9. Population-based studies and multicentre observational cohort series provide improved understanding of the clinical course that patients experience, highlighting variations in presenting phenotypes geographically and temporally. Collectively, while autoimmune liver diseases are rare, the clinical burden is disproportionately high relative to population incidence and prevalence. Age, sex and race also impact clinical outcomes, and patient morbidity and mortality are reflected by high need for gastroenterology, hepatology and organ transplant services.
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Affiliation(s)
- Palak J Trivedi
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre, University of Birmingham College of Medical and Dental Sciences, Birmingham, Birmingham, UK
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, UK
| | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Ontario, Canada
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19
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Alswat K, Soliman E, Salih I, Bashmail A, Letierce A, Benmousa A, Alghamdi S, Bzeizi KI, Alqahtani SA, Shawkat M, Broering DC, Al-Hamoudi WK. Long Term Outcomes of Liver Transplantation For Patients With Autoimmune Hepatitis. Transplant Proc 2021; 53:2339-2345. [PMID: 34474912 DOI: 10.1016/j.transproceed.2021.07.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 07/19/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). Data on the long-term outcomes of living-related LT for AIH are limited and inconsistent. The present study aimed to assess the long-term outcomes of deceased donor LT (DDLT) and living donor LT (LDLT) for AIH. METHODS All patients who received transplants for AIH-related cirrhosis from 2001 to 2018 were included in this study. RESULTS Seventy-four patients (31 male, 43 female) received LT. The average follow-up was 7.9 ± 6.9 years (median = 7.2 years), average age was 34.3 ± 13.8 years, and average Model for End-Stage Liver Disease (MELD) score was 23.6 ± 8.5. Thirty-six (49.3%) patients received a graft from a living donor, and 83% of patients were maintained on steroids. The 1-, 3-, 5-, and 10-year survival rates of patients were 91%, 89%, 87%, and 82% and of grafts were 89%, 88%, 86%, and 76%, respectively. In univariate analysis, MELD score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.17; P = .028), donor age (OR per 5 years, 1.45; 95% CI, 1.07-2.02; P = .021), donor type (OR LDLT vs DDLT, 0.19; 95% CI, 0.04-0.67; P = .017), and renal function (OR glomerular filtration rate <60 vs ≥60 mL/min/m2, 7.41; 95% CI, 1.88-31.25; P = .004) were significant predictors of graft survival; however, none of the factors remained significant in multivariate analysis. CONCLUSION We have shown the highest reported long-term survival rates in LT for AIH, including a large number of patients who underwent LDLT. Standardized management and immunosuppressive therapy, including the maintenance of a low-dose steroid protocol, may have contributed to this outcome.
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Affiliation(s)
- Khalid Alswat
- Department of Medicine, King Saud University, College of Medicine, Liver Disease Research Center, Riyadh, Saudi Arabia.
| | - Elvy Soliman
- Liver Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Internal Medicine, Minia University, Egypt
| | - Isam Salih
- Liver Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Ahmed Bashmail
- Department of Medicine, King Saud University, College of Medicine, Liver Disease Research Center, Riyadh, Saudi Arabia
| | | | - Ali Benmousa
- Liver Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Saad Alghamdi
- Liver Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Khalid I Bzeizi
- Liver Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Saleh A Alqahtani
- Liver Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland
| | - Mohamed Shawkat
- Liver Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Internal Medicine, Minia University, Egypt
| | - Dieter C Broering
- Liver Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Waleed K Al-Hamoudi
- Department of Medicine, King Saud University, College of Medicine, Liver Disease Research Center, Riyadh, Saudi Arabia; Liver Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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20
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HLA-DR Mismatch and Black Race Are Associated With Recurrent Autoimmune Hepatitis After Liver Transplantation. Transplant Direct 2021; 7:e714. [PMID: 34131586 PMCID: PMC8196096 DOI: 10.1097/txd.0000000000001160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 03/30/2021] [Indexed: 01/02/2023] Open
Abstract
Supplemental Digital Content is available in the text. The predictors of recurrent autoimmune hepatitis (R-AIH) after liver transplantation (LT) are heterogeneous with limited data to guide immunosuppression, with little data on impact of race.
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21
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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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22
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Wang G, Tanaka A, Zhao H, Jia J, Ma X, Harada K, Wang FS, Wei L, Wang Q, Sun Y, Hong Y, Rao H, Efe C, Lau G, Payawal D, Gani R, Lindor K, Jafri W, Omata M, Sarin SK. The Asian Pacific Association for the Study of the Liver clinical practice guidance: the diagnosis and management of patients with autoimmune hepatitis. Hepatol Int 2021; 15:223-257. [PMID: 33942203 PMCID: PMC8144150 DOI: 10.1007/s12072-021-10170-1] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 02/27/2021] [Indexed: 02/06/2023]
Affiliation(s)
- Guiqiang Wang
- Peking University First Hospital, Beijing, China.
- Peking University International Hospital, Beijing, China.
| | | | - Hong Zhao
- Peking University First Hospital, Beijing, China
- Peking University International Hospital, Beijing, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiong Ma
- Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Kenichi Harada
- Department of Human Pathology, Kanazawa University Graduate School of Medicine Kanazawa, Kanazawa, Japan
| | - Fu-Sheng Wang
- Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lai Wei
- Beijing Tsinghua Changgung Hospital, Beijing, China
| | - Qixia Wang
- Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Sun
- Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yuan Hong
- Peking University First Hospital, Beijing, China
| | - Huiying Rao
- Peking University People's Hospital, Beijing, China
| | - Cumali Efe
- Department of Gastroenterology, Harran University, Şanlıurfa, Turkey
| | - George Lau
- Humanity and Health Medical Group, Hong Kong Special Administrative Region, China
| | - Diana Payawal
- Department of Hepatology, Cardinal Santos Medical Center, Manila, Philippines
| | - Rino Gani
- Department of Internal Medicine, Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta, Indonesia
| | - Keith Lindor
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
| | | | - Masao Omata
- Department of Gastroenterology, Yamanashi Prefectural Central Hospital, Kofu-City, Yamanashi, Japan
- The University of Tokyo, Tokyo, Japan
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23
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Rahim MN, Miquel R, Heneghan MA. Approach to the patient with acute severe autoimmune hepatitis. JHEP Rep 2020; 2:100149. [PMID: 32995712 PMCID: PMC7509236 DOI: 10.1016/j.jhepr.2020.100149] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 07/09/2020] [Accepted: 07/15/2020] [Indexed: 12/11/2022] Open
Abstract
Autoimmune hepatitis is associated with varied clinical presentations and natural history, as well as somewhat unpredictable treatment responses. Understanding how to stratify patients who require further escalation of therapy will help clinicians manage these patients. The presentation of acute severe autoimmune hepatitis (AS-AIH) is relatively uncommon, although its prevalence is potentially greater than currently perceived. Previous studies consist of small retrospective single-centre series and are not directly comparable due to the diversity of presentations, disease definitions and non-standardised treatment regimens. We define AS-AIH as those who present acutely with AIH and are icteric with an international normalised ratio ≥1.5 and no evidence of hepatic encephalopathy. Those with hepatic encephalopathy should be defined as having AS-AIH with acute liver failure. In this review, we provide a structured practical approach for diagnosing and managing this unique group of patients.
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Key Words
- ACLF, acute-on-chronic liver failure
- AIH, autoimmune hepatitis
- ALF, acute liver failure
- ALI, acute liver injury
- ALT, alanine aminotransferase
- ANA, anti-nuclear antibody
- AS-AIH, acute severe autoimmune hepatitis
- ASMA, anti-smooth muscle antibody
- AST, aspartate aminotransferase
- AUROC, analysis of area under the receiver operator characteristic curve
- Acute liver failure
- Acute severe presentation
- Autoimmune hepatitis
- CT, computed tomography
- Corticosteroids
- DILI, drug-induced liver injury
- EBV, Epstein-Barr virus
- HE, hepatic encephalopathy
- HLA, human leukocyte antigen
- IAIHG, International Autoimmune Hepatitis Group
- INR, international normalised ratio
- LT, liver transplantation
- Liver transplantation
- MELD, model for end-stage liver disease
- MELD-Na, model for end-stage liver disease-sodium
- MHN, massive hepatic necrosis
- NAC, N-acetylcysteine
- PT, prothrombin time
- UKELD, United Kingdom end-stage liver disease
- USALF, United States Acute Liver Failure
- anti-LC-1, anti-liver cytosol-1
- anti-LKM, anti-liver kidney microsomal
- anti-SLA/LP, anti-soluble liver antigen/liver pancreas
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Affiliation(s)
- Mussarat N. Rahim
- Institute of Liver Studies, King's College Hospital, London, SE5 9RS, UK
| | - Rosa Miquel
- Liver Histopathology Laboratory, King's College Hospital, London, SE5 9RS, UK
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24
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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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25
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Vierling JM, Kerkar N, Czaja AJ, Mack CL, Adams D, Assis DN, Manns MP, Mayo MJ, Nayfeh T, Majzoub AMM, Alzuabi MA, Ding J, Haffar S, Murad MH, Alsawas M. Immunosuppressive Treatment Regimens in Autoimmune Hepatitis: Systematic Reviews and Meta-Analyses Supporting American Association for the Study of Liver Diseases Guidelines. Hepatology 2020; 72:753-769. [PMID: 32500593 DOI: 10.1002/hep.31407] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 04/30/2020] [Accepted: 05/26/2020] [Indexed: 12/13/2022]
Affiliation(s)
- John M Vierling
- Departments of Medicine and Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Nanda Kerkar
- Department of Pediatrics, University of Rochester School of Medicine, Rochester, NY, USA
| | - Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Cara L Mack
- Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA
| | - David Adams
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
| | - David N Assis
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Marlyn J Mayo
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Tarek Nayfeh
- Mayo Clinic Evidence-Based Practice Research Program, Rochester, MN, USA
| | | | - Muayad A Alzuabi
- Mayo Clinic Evidence-Based Practice Research Program, Rochester, MN, USA
| | - Jingyi Ding
- Mayo Clinic Evidence-Based Practice Research Program, Rochester, MN, USA
| | - Samir Haffar
- Mayo Clinic Evidence-Based Practice Research Program, Rochester, MN, USA
| | - M Hassan Murad
- Mayo Clinic Evidence-Based Practice Research Program, Rochester, MN, USA
| | - Mouaz Alsawas
- Mayo Clinic Evidence-Based Practice Research Program, Rochester, MN, USA
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26
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de Quadros Onofrio F, Neong E, Adebayo D, Kollmann D, Adeyi OA, Fischer S, Hirschfield GM, Hansen BE, Bhat M, Galvin Z, Lilly LB, Selzner N. Single-Center North American Experience of Liver Transplantation in Autoimmune Hepatitis: Infrequent Indication but Good Outcomes for Patients. J Can Assoc Gastroenterol 2020; 4:137-144. [PMID: 34056531 PMCID: PMC8158643 DOI: 10.1093/jcag/gwaa022] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background and Aims A 40% risk of disease recurrence post-liver transplantation (LT) for autoimmune hepatitis (AIH) has been previously reported. Risk factors for recurrence and its impact on long-term patient outcome are poorly defined. We aimed to assess prevalence, time to disease recurrence, as well as patient and graft survival in patients with recurrent AIH (rAIH) versus those without recurrence. Methods Single-center retrospective study of adult recipients who underwent LT for AIH between January 2007 and December 2017. Patients with AIH overlap syndromes were excluded. Results A total of 1436 LTs were performed during the study period, of whom 46 (3%) for AIH. Eight patients had AIH overlap syndromes and were excluded. Patients were followed up for 4.4 ± 3.4 years and mean age at LT was 46.8 years. Average transplant MELD (Model for End-Stage Liver Disease) score was 24.9. About 21% of patients (8 of 38) were transplanted for acute onset of AIH; 66% of patients (n = 25) received a deceased donor liver graft, and 34% a living donor organ. rAIH occurred in 7.8% (n = 3/38) of recipients. Time to recurrence was 1.6, 12.2 and 60.7 months. Patient and graft survival in patients without recurrence was 88.6% and 82.8% in 5 years, whereas in those with rAIH, it was 66.7%, respectively. Conclusion Although AIH recurs post-LT, our data indicate a lower recurrence rate when compared to the literature and excellent patient and graft survival.
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Affiliation(s)
| | - Evon Neong
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Danielle Adebayo
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Dagmar Kollmann
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Oyedele Adewale Adeyi
- Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA
| | - Sandra Fischer
- Department of Pathology, University Health Network, Toronto, Ontario, Canada
| | | | - Bettina Elisabeth Hansen
- Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
- IHPME, University of Toronto, Toronto, Ontario, Canada
| | - Mamatha Bhat
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Zita Galvin
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Leslie Blake Lilly
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Nazia Selzner
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Correspondence: Nazia Selzner, MD PhD, Multiorgan Transplant Program, University Health Network, 585 University Ave., 11 PMB 202, Toronto, ON M5G 2N2, Canada, e-mail:
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Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease, characterized by the elevation of aminotransferases, presence of anti-nuclear antibody or anti-smooth muscle antibody, elevated immunoglobulin G (IgG), and interface hepatitis/plasma-lymphocytic inflammation based on histology. Recent epidemiological studies have indicated an increasing trend in the prevalence of AIH worldwide, especially in male patients; this trend may suggest the alteration of environmental triggers of disease onset over time. As no disease-specific biomarker or histological finding is currently available, AIH requires a clinical diagnosis, and a validated diagnostic scoring system with acceptable specificity and sensitivity has been proposed. Regarding treatment, corticosteroids and azathioprine are recommended, and in those who exhibit an incomplete response or those who are intolerant to these drugs, second-line therapy, such as mycophenolate mofetil, is considered. Overall, the long-term outcome is excellent in patients with complete biochemical responses, while life-long maintenance treatment may be required since the cessation of immunosuppressive agents frequently leads to the relapse of the disease. Acute-onset AIH does occur, and the diagnosis is very challenging due to the lack of serum autoantibodies or elevated IgG. The unmet needs include earlier diagnosis, intervention with disseminated clinical practice guidelines, and recognition and improvement of patients’ health-related quality of life with the development of novel corticosteroid-free treatment regimens.
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Affiliation(s)
- Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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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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29
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Doycheva I, Watt KD, Gulamhusein AF. Autoimmune hepatitis: Current and future therapeutic options. Liver Int 2019; 39:1002-1013. [PMID: 30716203 DOI: 10.1111/liv.14062] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Revised: 01/13/2019] [Accepted: 01/17/2019] [Indexed: 02/13/2023]
Abstract
Autoimmune hepatitis (AIH) is a rare immune-mediated liver disease with few major advances in treatment options over the last several decades. Available options are effective in most patients albeit are imprecise in their mechanisms. Novel and more tolerable induction regimens and alternative options for management of patients intolerant or with suboptimal response to traditional therapies including in the post-transplant setting remain an important unmet need. This review aims to summarize recent data on pharmacological options and investigational drugs in development for patients with AIH. Standard therapy using prednisone with or without azathioprine remains the mainstay of therapy and is effective in most patients. Budesonide may be considered for induction in early disease and in those with mild fibrosis, but has not been approved for maintenance therapy. Mycophenolate mofetil (MMF) in combination with steroids might be an alternative first-line therapy, but results from a randomized trial are awaited. MMF as a second-line maintenance agent has moderate efficacy though more frequent adverse events in patients with cirrhosis may be seen. Tacrolimus may be an equally effective second-line option particularly in non-responders, but data remain limited. Management of recurrent AIH post-liver transplantation remains controversial with insufficient data to support long-term steroid use. Moving forward, expanding the scope of therapeutic options to include biologics including B-cell depleting agents may be a promising step. Recent insights in understanding the pathogenesis of AIH could serve as a basis for future therapies, including the elucidation of different immunoregulatory pathways and the potential role of the intestinal microbiome.
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Affiliation(s)
- Iliana Doycheva
- Division of Gastroenterology and Hepatology, Medical University, Sofia, Bulgaria
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Aliya F Gulamhusein
- Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto, ON, Canada
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30
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Rahim MN, Liberal R, Miquel R, Heaton ND, Heneghan MA. Acute Severe Autoimmune Hepatitis: Corticosteroids or Liver Transplantation? Liver Transpl 2019; 25:946-959. [PMID: 30900368 DOI: 10.1002/lt.25451] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 03/17/2019] [Indexed: 12/13/2022]
Abstract
Acute severe presentations of autoimmune hepatitis (AIH) represent a challenge for the transplant community. As a disease, it is poorly characterized, and there is a weak evidence base to guide diagnosis and treatment. Early identification of acute severe AIH is key because it determines the initiation of corticosteroids, which can be lifesaving. However, their use in this setting remains controversial. The Model for End-Stage Liver Disease score, severity of coagulopathy, and grade of encephalopathy may be predictors of outcome with corticosteroid therapy. The optimal timing of liver transplantation (LT) can be difficult to determine and, as such, the decision to proceed to transplantation should not be delayed by protracted courses of corticosteroids. The aim of this review is to better characterize this subset of patients; to differentiate them clinically, serologically, and histologically from chronic AIH and other causes of acute liver failure; and to present the role, predictors, and optimal timings of corticosteroid therapy and LT. Although this review is specific to adults, many principles hold true for the pediatric population.
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Affiliation(s)
- Mussarat N Rahim
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
| | - Rodrigo Liberal
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
| | - Rosa Miquel
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
| | - Nigel D Heaton
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
| | - Michael A Heneghan
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
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31
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Webb GJ, Hirschfield GM, Krawitt EL, Gershwin ME. Cellular and Molecular Mechanisms of Autoimmune Hepatitis. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2019; 13:247-292. [PMID: 29140756 DOI: 10.1146/annurev-pathol-020117-043534] [Citation(s) in RCA: 87] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Autoimmune hepatitis is an uncommon idiopathic syndrome of immune-mediated destruction of hepatocytes, typically associated with autoantibodies. The disease etiology is incompletely understood but includes a clear association with human leukocyte antigen (HLA) variants and other non-HLA gene variants, female sex, and the environment. Pathologically, there is a CD4+ T cell-rich lymphocytic inflammatory infiltrate with variable hepatocyte necrosis and subsequent hepatic fibrosis. Attempts to understand pathogenesis are informed by several monogenetic syndromes that may include autoimmune liver injury, by several drug and environmental agents that have been identified as triggers in a minority of cases, by human studies that point toward a central role for CD4+ effector and regulatory T cells, and by animal models of the disease. Nonspecific immunosuppression is the current standard therapy. Further understanding of the disease's cellular and molecular mechanisms may assist in the design of better-targeted therapies, aid the limitation of adverse effects from therapy, and inform individualized risk assessment and prognostication.
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Affiliation(s)
- G J Webb
- National Institute for Health Research Liver Biomedical Research Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom; ,
| | - G M Hirschfield
- National Institute for Health Research Liver Biomedical Research Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom; ,
| | - E L Krawitt
- Department of Medicine, University of Vermont, Burlington, Vermont 05405, USA; .,Department of Medicine, Dartmouth College, Hanover, New Hampshire 03755, USA
| | - M E Gershwin
- Division of Rheumatology, Allergy, and Clinical Immunology, School of Medicine, University of California, Davis, California 95817, USA;
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32
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Stirnimann G, Ebadi M, Czaja AJ, Montano-Loza AJ. Recurrent and De Novo Autoimmune Hepatitis. Liver Transpl 2019; 25:152-166. [PMID: 30375180 DOI: 10.1002/lt.25375] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 10/23/2018] [Indexed: 02/07/2023]
Abstract
Clinical indications for liver transplantation (LT) in patients with autoimmune hepatitis (AIH) are identical to those of patients with other chronic liver diseases that end in acute or semiacute liver failure, decompensated cirrhosis, or hepatocellular carcinoma. Recurrent disease after LT has been reported in 10%-50% of patients with AIH, and the frequency of detection is influenced in part by the use of protocol or clinically indicated liver biopsy. De novo AIH connotes the development of AIH in patients transplanted for liver diseases other than AIH, and it has been reported in 5%-10% of pediatric and 1%-2% of adult recipients. Recurrent disease can negatively impact on graft and patient survival, and retransplantation has been required in 8%-23%. De novo AIH is within the spectrum of graft dysfunction that includes plasma cell-rich rejection, and it can also progress to cirrhosis and graft failure. Treatment for recurrent or de novo disease is based on the conventional regimens for AIH, and corticosteroid therapy alone or combined with azathioprine is standard. Better control of disease activity prior to LT has been associated with less recurrence, and maintenance corticosteroid treatment after LT can reduce its frequency. In conclusion, recurrent AIH is far more frequent than de novo AIH. Both may have negative impacts on graft and patient survival, and early detection and treatment are key objectives. Future investigations must codify the diagnostic criteria for each graft dysfunction, seek diagnostic biomarkers, and evaluate treatments that improve outcomes without increasing the risk of pre- and post-LT infections.
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Affiliation(s)
- Guido Stirnimann
- Department of Visceral Surgery and Medicine, Inselspital Bern, Bern University Hospital and University of Bern, Bern, Switzerland.,Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton, Alberta, Canada
| | - Maryam Ebadi
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton, Alberta, Canada
| | - Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN
| | - Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton, Alberta, Canada
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33
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Aljumah AA, Al Jarallah B, Albenmousa A, Al Khathlan A, Al Zanbagi A, Al Quaiz M, Al-Judaibi B, Nabrawi K, Al Hamoudi W, Alghamdi M, Fallatah H. The Saudi association for the study of liver diseases and transplantation clinical practice guidelines for management of autoimmune hepatitis. Saudi J Gastroenterol 2018; 24:S1-S20. [PMID: 30264737 PMCID: PMC6305081 DOI: 10.4103/sjg.sjg_159_18] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Abdulrahman A. Aljumah
- Division of Hepatology, Hepatobiliary Sciences and Organ Transplant Center, King Abdulaziz Medical City and King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Badr Al Jarallah
- Department of Medicine, Division of Gastroenterology, Al Qassim University, Al Qassim, Saudi Arabia
| | - Ali Albenmousa
- Department of Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Abdullah Al Khathlan
- Department of Medicine, Division of Gastroenterology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Adnan Al Zanbagi
- Department of Medicine, Division of Gastroenterology, King Abdullah Medical City, Makkah, Saudi Arabia
| | - Mohammed Al Quaiz
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Bandar Al-Judaibi
- Department of Medicine, University of Rochester, Rochester City, New York State, USA
| | - Khalid Nabrawi
- Department of Internal Medicine, Aseer Central Hospital, Abha, Saudi Arabia
| | - Waleed Al Hamoudi
- Department of Medicine, Division of Gastroenterology, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Alghamdi
- Department of Internal Medicine, King Fahad Military Medical City, Dhahran, Saudi Arabia
| | - Hind Fallatah
- Department of Medicine, Division of Gastroenterology and Hepatology, King Abdulaziz University, Jeddah, Saudi Arabia
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34
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Theocharidou E, Heneghan MA. Con: Steroids Should Not Be Withdrawn in Transplant Recipients With Autoimmune Hepatitis. Liver Transpl 2018; 24:1113-1118. [PMID: 29893056 DOI: 10.1002/lt.25205] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 03/19/2018] [Accepted: 03/31/2018] [Indexed: 02/07/2023]
Abstract
Autoimmune liver diseases (AILDs) can recur following liver transplantation (LT) despite immunosuppressive therapy, with implications for graft survival. Although the evidence is not robust, disease recurrence seems to occur in the presence of less intense and/or steroid-free immunosuppression (IS) in particular in the case of autoimmune hepatitis (AIH). The main risk factor for AIH recurrence is the severity of disease activity in the explant and potential donor/recipient human leukocyte antigen D-related 3 (DR3) mismatch. The treatment for AIH recurrence includes reintroduction or increase in the dose of steroids with or without the addition of azathioprine. T cell-mediated rejection episodes are also more common in AILD. Steroid withdrawal is the common practice in LT for non-AILD, eliminating the risks associated with longterm exposure to steroids. In AILD, maintenance of steroids at a low dose in the long term may reduce the risk of disease recurrence and rejection. This strategy is safe when there is vigilance for steroid-related adverse effects. Alternatively, identifying patients who are at the greatest risk for disease recurrence and who would benefit from intensified IS might be an option.
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Affiliation(s)
- Eleni Theocharidou
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
| | - Michael A Heneghan
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
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35
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Czaja AJ. Emerging therapeutic biomarkers of autoimmune hepatitis and their impact on current and future management. Expert Rev Gastroenterol Hepatol 2018. [PMID: 29540068 DOI: 10.1080/17474124.2018.1453356] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Autoimmune hepatitis lacks a quantifiable biomarker that is close to its pathogenic mechanisms and that accurately reflects inflammatory activity, correlates with treatment response, and ensures inactive disease before treatment withdrawal. Areas covered: Micro-ribonucleic acids, programmed death-1 protein and its ligands, macrophage migration inhibitory factor, soluble CD163, B cell activating factor, and metabolite patterns in blood were considered the leading candidates as therapeutic biomarkers after search of PubMed from August 1981 to August 2017 using the search words 'biomarkers of autoimmune hepatitis'. Expert commentary: Each of the candidate biomarkers is close to the putative pathogenic mechanisms of autoimmune hepatitis, and each has attributes that support its potential role as a surrogate marker of inflammatory activity that can be monitored during treatment. Future studies must demonstrate the superiority of each biomarker to conventional indices of inflammatory activity and validate their correlation with treatment response and outcome. A reliable therapeutic biomarker would facilitate the individualization of current management algorithms, ensure that pathogenic mechanisms were disrupted or eliminated prior to treatment withdrawal, and reduce the frequency of relapse or unnecessary protracted therapy. The biomarker might also prove to be a target of next-generation therapies.
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Affiliation(s)
- Albert J Czaja
- a Division of Gastroenterology and Hepatology , Mayo Clinic College of Medicine and Science , Rochester , MN , USA
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36
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Mieli-Vergani G, Vergani D, Baumann U, Czubkowski P, Debray D, Dezsofi A, Fischler B, Gupte G, Hierro L, Indolfi G, Jahnel J, Smets F, Verkade HJ, Hadžić N. Diagnosis and Management of Pediatric Autoimmune Liver Disease: ESPGHAN Hepatology Committee Position Statement. J Pediatr Gastroenterol Nutr 2018; 66:345-360. [PMID: 29356770 DOI: 10.1097/mpg.0000000000001801] [Citation(s) in RCA: 192] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Paediatric autoimmune liver disease is characterized by inflammatory liver histology, circulating autoantibodies, and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis, and de novo AIH after liver transplantation. Two types of pediatric AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (AIH-1) or liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibodies (AIH-2).Pertinent issues addressing the diagnosis, treatment, and long-term follow-up were formulated by a core group of ESPGHAN members. They have commissioned the first authors with execution of this project. Initially, they have performed a systematic literature search on MEDLINE, ResearchGate, and Mendeley databases during the last 30 years and produced a document focusing on prospective and retrospective studies in children. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique.
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Affiliation(s)
| | - Diego Vergani
- MowatLabs, Paediatric Liver, GI & Nutrition Centre, King's College Hospital, London, UK
| | - Ulrich Baumann
- Pädiatrische Gastroenterologie und Hepatologie, Medizinische Hochschule, Hannover, Germany
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology, Nutrition Disturbances and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Dominique Debray
- Pediatric Hepatology Unit, AP-HP-Hôpital Necker Enfants Malades, Paris, France
| | - Antal Dezsofi
- First Department of Paediatrics, Semmelweis University, Budapest, Hungary
| | - Björn Fischler
- Department of Pediatrics, Karolinska University Hospital, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Girish Gupte
- Liver Unit (Including Small Bowel Transplantation), Department of Gastroenterology and Nutrition, Birmingham Children's Hospital, Birmingham, UK
| | - Loreto Hierro
- Hospital Infantil Universitario La Paz, Madrid, Spain
| | - Giuseppe Indolfi
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy
| | - Jörg Jahnel
- Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Françoise Smets
- UCL, Cliniques Universitaires Saint-Luc, Pediatric Gastroenterology and Hepatology, Brussels, Belgium
| | - Henkjan J Verkade
- Dept of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, the Netherlands
| | - Nedim Hadžić
- MowatLabs, Paediatric Liver, GI & Nutrition Centre, King's College Hospital, London, UK
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37
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Wagener G. Immunosuppression. LIVER ANESTHESIOLOGY AND CRITICAL CARE MEDICINE 2018. [PMCID: PMC7123053 DOI: 10.1007/978-3-319-64298-7_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Gebhard Wagener
- Department of Anesthesiology, Columbia University Medical Center, New York, New York USA
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38
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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39
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Sebode M, Hartl J, Vergani D, Lohse AW. Autoimmune hepatitis: From current knowledge and clinical practice to future research agenda. Liver Int 2018; 38:15-22. [PMID: 28432836 DOI: 10.1111/liv.13458] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 04/12/2017] [Indexed: 12/12/2022]
Abstract
Autoimmune hepatitis is a chronic inflammatory liver disease. Unknown triggers lead to a mainly T cell-mediated immune response targeting the liver, the main auto-antigen of which has not been identified yet. The diagnosis of autoimmune hepatitis is based on the elevation of immunoglobulin G/hypergammaglobulinemia, detection of characteristic autoantibodies as well as a typical pattern on liver histology. Exclusion of other causes of hepatitis and response to immunosuppressive treatment support the diagnosis of autoimmune hepatitis. The mainstay of autoimmune hepatitis treatment has, from its first description to the current time, consisted of predniso(lo)ne to induce remission, in combination with azathioprine, which is used to maintain it. Nonetheless, side effects and non-response with ongoing inflammation despite standard therapy demand treatment alternatives. Only through a better understanding of the pathogenesis of autoimmune hepatitis can a more selective and effective treatment be offered to patients in the future. Until this goal is reached, improvement of diagnostic approaches and optimization of current therapy rank highest on the research agenda for autoimmune hepatitis.
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Affiliation(s)
- Marcial Sebode
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Johannes Hartl
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Diego Vergani
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Ansgar W Lohse
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
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40
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Díaz-Ramírez GS, Marín-Zuluaga JI, Donado-Gómez JH, Muñoz-Maya O, Santos-Sánchez Ó, Restrepo-Gutiérrez JC. Characterization of patients with autoimmune hepatitis at an university hospital in Medellín-Colombia: cohort study. GASTROENTEROLOGIA Y HEPATOLOGIA 2017; 41:87-96. [PMID: 29126693 DOI: 10.1016/j.gastrohep.2017.09.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 08/17/2017] [Accepted: 09/15/2017] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Autoimmune hepatitis is a chronic liver disease that impacts on morbidity and mortality of patients. Few epidemiological data exist of this in Latin America and Colombia. OBJECTIVES The aim of this study is to describe the demographic, clinical and laboratory characteristics of the patients; the treatment and the response to it, the evolution and course of the disease, requirement of liver transplantation and mortality. METHODS Historical cohort study that include patients attended at an University Hospital in Medellin, Colombia between January 2010 and December 2016 with ≥16 years age at the time of diagnosis of autoimmune hepatitis. Data collection was done from the review of medical records. Statistical analysis was performed using SPSS version 20. RESULTS The study included 278 patients, 90% of the patients were women, the median age at diagnosis was 50 years. 37.8% were cirrhotic at the time of diagnosis. The biochemical remission was 85%. In patients who developed cirrhosis it was found a higher proportion of men (21.2 vs. 7.8%, p=.027), a greater frequency of overlap autoimmune-primary sclerosant cholangitis (6.0 vs. 0% p=.006) and a greater frequency of non-response to treatment (12.1 vs. 1.6%, p=.004). CONCLUSION Autoimmune hepatitis is not a rare disease in Colombian population; it predominates in women but has a less favourable course in men. An important number of patients are cirrhotic at the time of diagnosis, the response to treatment and complications in our population are similar to those described worldwide.
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Affiliation(s)
| | - Juan Ignacio Marín-Zuluaga
- Grupo de Gastrohepatología, Universidad de Antioquia, Medellín, Colombia; Unidad de Hepatología y Trasplante Hepático, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | | | - Octavio Muñoz-Maya
- Grupo de Gastrohepatología, Universidad de Antioquia, Medellín, Colombia; Unidad de Hepatología y Trasplante Hepático, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - Óscar Santos-Sánchez
- Grupo de Gastrohepatología, Universidad de Antioquia, Medellín, Colombia; Unidad de Hepatología y Trasplante Hepático, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - Juan Carlos Restrepo-Gutiérrez
- Grupo de Gastrohepatología, Universidad de Antioquia, Medellín, Colombia; Unidad de Hepatología y Trasplante Hepático, Hospital Pablo Tobón Uribe, Medellín, Colombia
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41
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Strasser SI. Longterm outcome of the liver graft: A clinician's perspective-recurrent disease, the universal shifting. Liver Transpl 2017; 23:S64-S69. [PMID: 28779560 DOI: 10.1002/lt.24839] [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: 07/24/2017] [Accepted: 08/03/2017] [Indexed: 01/13/2023]
Affiliation(s)
- Simone I Strasser
- AW Morrow Gastroenterology and Liver Centre, Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
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Montano‐Loza AJ, Mason AL. Recurrence of primary biliary cholangitis after liver transplantation: A Japanese perspective. Hepatol Commun 2017; 1:391-393. [PMID: 29404467 PMCID: PMC5721417 DOI: 10.1002/hep4.1058] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Accepted: 05/19/2017] [Indexed: 01/23/2023] Open
Affiliation(s)
- Aldo J. Montano‐Loza
- Division of Gastroenterology and Liver UnitUniversity of Alberta HospitalEdmontonCanada
| | - Andrew L. Mason
- Division of Gastroenterology and Liver UnitUniversity of Alberta HospitalEdmontonCanada
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Satapathy SK, Jones OD, Vanatta JM, Kamal F, Kedia SK, Jiang Y, Nair SP, Eason JD. Outcomes of Liver Transplant Recipients With Autoimmune Liver Disease Using Long-Term Dual Immunosuppression Regimen Without Corticosteroid. Transplant Direct 2017; 3:e178. [PMID: 28706981 PMCID: PMC5498019 DOI: 10.1097/txd.0000000000000693] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 04/15/2017] [Accepted: 05/01/2017] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Liver transplant (LT) recipients with autoimmune liver disease (primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis) are at increased risk of developing acute cellular rejection (ACR), and in many cases graft failure due to recurrent disease. We describe our experience with dual immunosuppression without steroid maintenance and analyze its effect on disease recurrence; ACR; patient and graft survivals; and complications, such as sepsis and de novo malignancy. METHODS We included 74 consecutive LT recipients (April 2006 to April 2013) with autoimmune liver disease (primary sclerosing cholangitis, 20; primary biliary cholangitis, 23; autoimmune hepatitis, 31) from a single transplant center. Immunosuppression protocol included rabbit antithymocyte globulin for induction and mycophenolate mofetil with tacrolimus or sirolimus/everolimus indefinitely for maintenance. RESULTS Overall 1-, 3-, 5-, and 7-year patient survival was 95.9%, 90.4%, 82,2% and 74.9%, re-graft-free survival was 93.2%, 86.3%, 79.9%, and 72.8%, respectively (median follow-up, 5.5 years). In a multivariate Cox regression analysis, sepsis during post-LT period (P = 0.040; hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.04-6.11), steroid use for ACR (P = 0.037; HR, 2.60; 95% CI, 1.06-6.34), and younger age (<40 years) at LT (P = 0.038; HR, 2.53; 95% CI, 1.05-6.10) predicted graft survival, whereas steroid use for ACR was the only variable that was predictive of overall patient survival (P = 0.004; HR, 4.10; 95% CI, 1.59-10.52). Overall, 34 biopsy-proven ACR was noted in 22 LT recipients (30%), 13 (17.5%) had disease recurrence, and 34 episodes of sepsis occurred in 19 patients. CONCLUSIONS Dual immunosuppression protocol in LT recipients with autoimmune liver disease without corticosteroid maintenance had acceptable rates of survival and ACR without predisposing patients to the adverse effects of long-term steroid therapy.
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Affiliation(s)
- Sanjaya K. Satapathy
- Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN
| | - Ollie D. Jones
- Department of Gastroenterology, University of Tennessee Health Sciences Center, Memphis, TN
| | - Jason M. Vanatta
- Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN
| | - Faisal Kamal
- Department of Internal Medicine, University of Tennessee Health Sciences Center, Memphis, TN
| | | | - Yu Jiang
- School of Public Health, University of Memphis, Memphis, TN
| | - Satheesh P. Nair
- Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN
| | - James D. Eason
- Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN
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Abstract
Recurrent autoimmune hepatitis (AIH) and de novo AIH are 2 important causes of late graft failure after liver transplantation (LT). Recurrent AIH occurs in patients who undergo LT for AIH. De novo AIH occurs in patients who are transplanted for etiologies other than AIH. Although typically treated with standard treatment for AIH, including corticosteroids and azathioprine, both recurrent and de novo AIH may progress to end-stage liver disease requiring retransplantation.
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Affiliation(s)
- Eliza W Beal
- Division of Transplantation, Department of Surgery, The Ohio State University Wexner Medical Center, 395 West 12th Avenue, Suite 100, Columbus, OH 43210, USA
| | - Sylvester M Black
- Division of Transplantation, Department of Surgery, The Ohio State University Wexner Medical Center, 395 West 12th Avenue, Suite 100, Columbus, OH 43210, USA
| | - Anthony Michaels
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, 395 West 12th Avenue, Suite 200, Columbus, OH 43210, USA.
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45
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Puustinen L, Boyd S, Arkkila P, Isoniemi H, Arola J, Färkkilä M. Histologic surveillance after liver transplantation due to autoimmune hepatitis. Clin Transplant 2017; 31. [DOI: 10.1111/ctr.12936] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/19/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Lauri Puustinen
- Department of Gastroenterology; Helsinki University Hospital; Helsinki Finland
| | - Sonja Boyd
- Department of Pathology; University of Helsinki; Helsinki University Hospital; Helsinki Finland
| | - Perttu Arkkila
- Department of Gastroenterology; Helsinki University Hospital; Helsinki Finland
| | - Helena Isoniemi
- Department of Hepatobiliary Surgery; Helsinki University Hospital; Helsinki Finland
| | - Johanna Arola
- Department of Pathology; University of Helsinki; Helsinki University Hospital; Helsinki Finland
| | - Martti Färkkilä
- Department of Gastroenterology; Helsinki University Hospital; Helsinki Finland
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Visseren T, Darwish Murad S. Recurrence of primary sclerosing cholangitis, primary biliary cholangitis and auto-immune hepatitis after liver transplantation. Best Pract Res Clin Gastroenterol 2017. [PMID: 28624107 DOI: 10.1016/j.bpg.2017.04.004] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Liver transplantation is a well-accepted treatment for decompensated chronic liver disease due to primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and auto-immune hepatitis (AIH). Survival after liver transplantation is generally good with 1 and 5-year survival rates around 90% and 70-85%. After transplantation, however, these diseases recur in 8.6-27% (rPSC), 10.9-42.3% (rPBC) and 7-42% (rAIH), and this poses significant challenges in terms of management and graft outcome in these patients. In this review we discuss the incidence, clinical presentation, challenges in diagnosis, reported risk factors and impact on post-transplant outcomes of recurrence of PSC, PBC and AIH after liver transplantation. We also discuss some of the limitations of current investigations and formulate idea's for future research objectives.
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Affiliation(s)
- T Visseren
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
| | - S Darwish Murad
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
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Liver Transplantation for Children With Primary Sclerosing Cholangitis and Autoimmune Hepatitis: UNOS Database Analysis. J Pediatr Gastroenterol Nutr 2017; 64:e83-e87. [PMID: 27755342 DOI: 10.1097/mpg.0000000000001438] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are progressive immune-mediated inflammatory diseases that may require liver transplant (LT). Outcomes in children undergoing LT for these diseases are poorly studied in the pediatric end-stage liver disease era. We aimed to characterize the outcome of LT in children with AIH and PSC. METHODS Children 18 years or younger with PSC or AIH who had a first, isolated LT from 2002 to 2012 were identified from the United Network for Organ Sharing database. Graft and patient outcomes were studied. RESULTS A total of 174 children with AIH and 113 with PSC were transplanted in the study period. One-year patient survival was 95.4% for AIH and 97.3% for PSC. Five-year patient survival was 91.4% for AIH and 92.9% for PSC. Patient survival was not significantly different between the 2 groups. Forty-four (25.2%) children with AIH were listed as status 1 for transplant (fulminant hepatic failure at presentation or acute-on-chronic disease). Patients transplanted as status 1 had significantly lower patient survival compared with patients transplanted with AIH and end-stage liver disease. The one- and five-year graft survival rates were not significantly different between patients with AIH and PSC. CONCLUSION Children with AIH transplanted as status 1 had significantly lower patient survival rates but similar graft survival rates to children with chronic AIH. Children transplanted for AIH versus PSC showed no significant differences in patient or graft survival at both 1 and 5 years.
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Montano-Loza AJ, Bhanji RA, Wasilenko S, Mason AL. Systematic review: recurrent autoimmune liver diseases after liver transplantation. Aliment Pharmacol Ther 2017; 45:485-500. [PMID: 27957759 DOI: 10.1111/apt.13894] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 10/21/2016] [Accepted: 11/17/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Autoimmune liver diseases (AILD) constitute the third most common indication for liver transplantation (LT) worldwide. Outcomes post LT are generally good but recurrent disease is frequently observed. AIMS To describe the frequency and risk factors associated with recurrent AILD post-LT and provide recommendations to reduce the incidence of recurrence based on levels of evidence. METHODS A systematic review was performed for full-text papers published in English-language journals, using the keywords 'autoimmune hepatitis (AIH)', 'primary biliary cholangitis and/or cirrhosis (PBC)', 'primary sclerosing cholangitis (PSC)', 'liver transplantation' and 'recurrent disease'. Management strategies to reduce recurrence after LT were classified according to grade and level of evidence. RESULTS Survival rates post-LT are approximately 90% and 70% at 1 and 5 years and recurrent disease occurs in a range of 10-50% of patients with AILD. Recurrent AIH is associated with elevated liver enzymes and IgG before LT, lymphoplasmacytic infiltrates in the explants and lack of steroids after LT (Grade B). Tacrolimus use is associated with increased risk; use of ciclosporin and preventive ursodeoxycholic acid with reduced risk of PBC recurrence (all Grade B). Intact colon, active ulcerative colitis and early cholestasis are associated with recurrent PSC (Grade B). CONCLUSIONS Recommendations based on grade A level of evidence are lacking. The need for further study and management includes active immunosuppression before liver transplantation and steroid use after liver transplantation in autoimmune hepatitis; selective immunosuppression with ciclosporin and preventive ursodeoxycholic acid treatment for primary biliary cholangitis; and improved control of inflammatory bowel disease or even colectomy in primary sclerosing cholangitis.
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Affiliation(s)
- A J Montano-Loza
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - R A Bhanji
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - S Wasilenko
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - A L Mason
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
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Montano-Loza AJ, Thandassery RB, Czaja AJ. Targeting Hepatic Fibrosis in Autoimmune Hepatitis. Dig Dis Sci 2016; 61:3118-3139. [PMID: 27435327 DOI: 10.1007/s10620-016-4254-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Accepted: 07/11/2016] [Indexed: 02/06/2023]
Abstract
Hepatic fibrosis develops or progresses in 25 % of patients with autoimmune hepatitis despite corticosteroid therapy. Current management regimens lack reliable noninvasive methods to assess changes in hepatic fibrosis and interventions that disrupt fibrotic pathways. The goals of this review are to indicate promising noninvasive methods to monitor hepatic fibrosis in autoimmune hepatitis and identify anti-fibrotic interventions that warrant evaluation. Laboratory methods can differentiate cirrhosis from non-cirrhosis, but their accuracy in distinguishing changes in histological stage is uncertain. Radiological methods include transient elastography, acoustic radiation force impulse imaging, and magnetic resonance elastography. Methods based on ultrasonography are comparable in detecting advanced fibrosis and cirrhosis, but their performances may be compromised by hepatic inflammation and obesity. Magnetic resonance elastography has excellent performance parameters for all histological stages in diverse liver diseases, is uninfluenced by inflammatory activity or body habitus, has been superior to other radiological methods in nonalcoholic fatty liver disease, and may emerge as the preferred instrument to evaluate fibrosis in autoimmune hepatitis. Promising anti-fibrotic interventions are site- and organelle-specific agents, especially inhibitors of nicotinamide adenine dinucleotide phosphate oxidases, transforming growth factor beta, inducible nitric oxide synthase, lysyl oxidases, and C-C chemokine receptors types 2 and 5. Autoimmune hepatitis has a pro-fibrotic propensity, and noninvasive radiological methods, especially magnetic resonance elastography, and site- and organelle-specific interventions, especially selective antioxidants and inhibitors of collagen cross-linkage, may emerge to strengthen current management strategies.
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Affiliation(s)
- Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - Ragesh B Thandassery
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - Albert J Czaja
- Professor Emeritus of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN, 55905, USA.
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Abstract
Autoimmune hepatitis (AIH) is a complex autoimmune disease characterized by immune-mediated destruction of hepatic parenchyma which can result in cirrhosis, liver failure, and death. Current American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of Liver (EASL) guidelines recommend corticosteroids alone or in combination with azathioprine as first-line treatment strategies. However, a significant proportion of patients may not be able to tolerate or achieve complete biochemical response with these options. In this article, we discuss approaches to these patients and other challenging AIH patient groups such as the asymptomatic, pregnant, elderly, and liver transplant recipients.
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