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Flatley S, Dixon S, Pilsworth E, Dube A, Hoeroldt B, Harrison L, Gleeson D. Diabetes Mellitus in Patients With Autoimmune Hepatitis: Frequency, Risk Factors and Effect on Outcome. Aliment Pharmacol Ther 2025. [PMID: 40342076 DOI: 10.1111/apt.70188] [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: 08/04/2024] [Revised: 09/02/2024] [Accepted: 04/30/2025] [Indexed: 05/11/2025]
Abstract
BACKGROUND Treatment for autoimmune hepatitis (AIH) includes corticosteroids, which are associated with the development of diabetes mellitus (DM). Reported new-onset DM rates in patients with AIH have varied, and predisposing factors and prognostic implications are inadequately characterised. AIM To identify the frequency and predisposing factors for DM in AIH and its association with disease progression and mortality. METHODS Retrospective/prospective single-centre study of 494 patients with AIH presenting 1987-2023, 466 receiving corticosteroids (454 prednisolone, 12 budesonide) and followed for (median (range) 9 (0-36) years). RESULTS Forty-seven patients (10%) already had DM at AIH diagnosis. New-onset DM subsequently developed in another 59 (13%). In those receiving prednisolone, new-onset DM incidence was 8% ± 1% after 1 year and 14% ± 2% after 10 years (14- and 3-fold higher than expected population rate), and was independently associated with older age, non-Caucasian ethnicity, higher initial prednisolone dose, higher BMI at diagnosis and more weight gain after 2 years of follow-up. New-onset DM usually persisted despite stopping prednisolone. New-onset DM and DM at any time were independently associated with all-cause death/transplantation rate, along with previously established risk factors (older age, cirrhosis, lower ALT at diagnosis and failure of early ALT normalisation). New-onset DM and DM at any time were also independently associated with cirrhosis development. Similar associations of new-onset DM and DM at any time with liver-related death/transplantation were significant on univariate but not multivariate analysis. CONCLUSION New-onset DM occurred in 13% of patients with AIH, was related to older age, non-Caucasian ethnicity, higher prednisolone dose, higher BMI at diagnosis and weight gain; and was an independent predictor of all-cause death/transplantation and of cirrhosis development, underlining the need to minimise steroid burden in AIH.
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Affiliation(s)
- Sarah Flatley
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, University of Sheffield Medical School, Sheffield, UK
| | - Selena Dixon
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Eleanor Pilsworth
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Asha Dube
- Department of Histopathology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Barbara Hoeroldt
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Laura Harrison
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Dermot Gleeson
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, University of Sheffield Medical School, Sheffield, UK
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Dalekos G, Gatselis N, Drenth JP, Heneghan M, Jørgensen M, Lohse AW, Londoño M, Muratori L, Papp M, Samyn M, Tiniakos D, Lleo A. EASL Clinical Practice Guidelines on the management of autoimmune hepatitis. J Hepatol 2025:S0168-8278(25)00173-4. [PMID: 40348684 DOI: 10.1016/j.jhep.2025.03.017] [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: 03/20/2025] [Accepted: 03/20/2025] [Indexed: 05/14/2025]
Abstract
Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology which may affect any patient irrespective of age, sex, and ethnicity. At baseline, the clinical spectrum of the disease varies largely from asymptomatic cases to acute liver failure with massive hepatocyte necrosis. The aim of these EASL guidelines is to provide updated guidance on the diagnosis and management of AIH both in adults and children. Updated guidance on the management of patients with variants and specific forms of AIH is also provided, as is detailed guidance on the management of AIH-associated cirrhosis, including surveillance for portal hypertension and hepatocellular carcinoma, as well as liver transplantation in decompensated cirrhosis.
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Chen Y, Chen R, Li H, Shuai Z. Clinical management of autoimmune liver diseases: juncture, opportunities, and challenges ahead. Immunol Res 2025; 73:67. [PMID: 40195209 PMCID: PMC11976385 DOI: 10.1007/s12026-025-09622-9] [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] [Received: 11/27/2024] [Accepted: 03/14/2025] [Indexed: 04/09/2025]
Abstract
The three major autoimmune liver diseases are autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC).These conditions are assumed to result from a breakdown in immunological tolerance, which leads to an inflammatory process that causes liver damage.The self-attack is started by T-helper cell-mediated identification of liver autoantigens and B-cell production of autoantibodies,and it is maintained by a reduction in the number and activity of regulatory T-cells.Infections and environmental factors have been explored as triggering factors for these conditions, in addition to a genetic predisposition.Allelic mutations in the HLA locus have been linked to vulnerability, as have relationships with single nucleotide polymorphisms in non-HLA genes.Despite the advances in the management of these diseases, there is no curative treatment for these disorders, and a significant number of patients eventually progress to an end-stage liver disease requiring liver transplantation.In this line, tailored immune-therapeutics have emerged as possible treatments to control the disease.In addition, early diagnosis and treatment are pivotal for reducing the long-lasting effects of these conditions and their burden on quality of life.Herein we present a review of the etiology, clinical presentation, diagnosis, and challenges on ALDs and the feasible solutions for these complex diseases.
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MESH Headings
- Humans
- Hepatitis, Autoimmune/therapy
- Hepatitis, Autoimmune/diagnosis
- Hepatitis, Autoimmune/immunology
- Hepatitis, Autoimmune/etiology
- Cholangitis, Sclerosing/therapy
- Cholangitis, Sclerosing/diagnosis
- Cholangitis, Sclerosing/immunology
- Liver Cirrhosis, Biliary/therapy
- Liver Cirrhosis, Biliary/diagnosis
- Liver Cirrhosis, Biliary/immunology
- Animals
- Immunotherapy/methods
- Autoimmune Diseases/therapy
- Autoimmune Diseases/diagnosis
- Disease Management
- Genetic Predisposition to Disease
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Affiliation(s)
- Yangfan Chen
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Ruofei Chen
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Haiyan Li
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Zongwen Shuai
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, 230032, China.
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Zhao X, Naghibzadeh M, Sun Y, Rahmani A, Lilly L, Selzner N, Tsien C, Jaeckel E, Vyas MP, Krishnan R, Hirschfield G, Bhat M. Machine Learning Prediction Model of Waitlist Outcomes in Patients with Primary Sclerosing Cholangitis. Transplant Direct 2025; 11:e1774. [PMID: 40166627 PMCID: PMC11957646 DOI: 10.1097/txd.0000000000001774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 01/01/2025] [Indexed: 04/02/2025] Open
Abstract
Background Liver transplantation is essential for many people with primary sclerosing cholangitis (PSC). People with PSC are less likely to receive a deceased donor liver transplant compared with other causes of chronic liver disease. This disparity may stem from the inaccuracy of the model for end-stage liver disease (MELD) in predicting waitlist mortality or dropout for PSC. The broad applicability of MELD across many causes comes at the expense of accuracy in prediction for certain causes that involve unique comorbidities. We aimed to develop a model that could more accurately predict dynamic changes in waitlist outcomes among patients with PSC while including complex clinical variables. Methods We developed 3 machine learning architectures using data from 4666 patients with PSC in the Scientific Registry of Transplant Recipients (SRTR) and tested our models on our institutional data set of 144 patients at the University Health Network (UHN). We evaluated their time-dependent concordance index (C-index) for mortality prediction and compared it against MELD-sodium and MELD 3.0. Results Random survival forest (RSF), a decision tree-based survival model, outperformed MELD-sodium and MELD 3.0 in both the SRTR and the UHN test data set using the same bloodwork variables and readily available demographic data. It achieved a C-index of 0.868 (SD 0.020) and 0.771 (SD 0.085) on the SRTR and UHN test data, respectively. Training a separate RSF model using the UHN data with PSC-specific achieved a C-index of 0.91. In addition to high MELD score, increased white blood cells, time on the waiting list, platelet count, presence of Autoimmune hepatitis-PSC overlap, aspartate aminotransferase, female sex, age, history of stricture dilation, and extremes of body weight were the top-ranked features predictive of the outcomes. Conclusions Our RSF model offers more accurate waitlist outcome prediction in PSC. The significant performance improvement with the inclusion of PSC-specific variables highlights the importance of disease-specific variables for predicting trajectories of clinically distinct presentations.
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Affiliation(s)
- Xun Zhao
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Maryam Naghibzadeh
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Yingji Sun
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Arya Rahmani
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Leslie Lilly
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Nazia Selzner
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Cynthia Tsien
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Elmar Jaeckel
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | | | - Rahul Krishnan
- Department of Computer Science, University of Toronto, Toronto, ON, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Gideon Hirschfield
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
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Gleeson D, Bornand R, Brownlee A, Dhaliwal H, Dyson JK, Hails J, Henderson P, Kelly D, Mells GF, Miquel R, Oo YH, Sutton A, Yeoman A, Heneghan MA. British Society of Gastroenterology guidelines for diagnosis and management of autoimmune hepatitis. Gut 2025:gutjnl-2024-333171. [PMID: 40169244 DOI: 10.1136/gutjnl-2024-333171] [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: 06/22/2024] [Accepted: 10/22/2024] [Indexed: 04/03/2025]
Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease which, if untreated, often leads to cirrhosis, liver failure and death. The last British Society of Gastroenterology (BSG) guideline for the management of AIH was published in 2011. Since then, our understanding of AIH has advanced in many areas. This update to the previous guideline was commissioned by the BSG and developed by a multidisciplinary group. The aim of this guideline is to review and summarise the current evidence, in order to inform and guide diagnosis and management of patients with AIH and its variant syndromes. The main focus is on AIH in adults, but the guidelines should also be relevant to older children and adolescents.
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Affiliation(s)
- Dermot Gleeson
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Division of Clinical Medicine, School of Medicine and Population Science, University of Sheffield, Sheffield, UK
| | | | | | - Harpreet Dhaliwal
- Department of Gastroenterology, Manchester Royal Infirmary, Manchester, UK
| | - Jessica K Dyson
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Janeane Hails
- Division of Gastroenterology and Hepatology, Addenbrooke's Hospital, Cambridge, UK
| | - Paul Henderson
- Royal Hospital for Children and Young People, Edinburgh, UK
| | - Deirdre Kelly
- Birmingham Women's & Children's Hospital, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - George F Mells
- Division of Gastroenterology and Hepatology, Addenbrooke's Hospital, Cambridge, UK
- Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK
| | - Rosa Miquel
- Liver Histopathology Laboratory, Institute of Liver Studies, King's College London, London, UK
| | - Ye H Oo
- Centre for Liver and Gastroenterology research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- NIHR Biomedical Research Centre, University of Birmingham and University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
- Centre for Rare Diseases, European Reference Network on Hepatological Diseases (ERN-RARE-LIVER) centre, Birmingham, UK
| | - Anthea Sutton
- Sheffield Centre for Health and Related Research, The University of Sheffield, Sheffield, UK
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Khendek L, Castro-Rojas C, Nelson C, Alquraish M, Karns R, Kasten J, Teng X, Miethke AG, Taylor AE. Quantitative fibrosis identifies biliary tract involvement and is associated with outcomes in pediatric autoimmune liver disease. Hepatol Commun 2025; 9:e0594. [PMID: 39670860 PMCID: PMC11637754 DOI: 10.1097/hc9.0000000000000594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 10/15/2024] [Indexed: 12/14/2024] Open
Abstract
BACKGROUND Children with autoimmune liver disease (AILD) may develop fibrosis-related complications necessitating a liver transplant. We hypothesize that tissue-based analysis of liver fibrosis by second harmonic generation (SHG) microscopy with artificial intelligence analysis can yield prognostic biomarkers in AILD. METHODS Patients from single-center studies with unstained slides from clinically obtained liver biopsies at AILD diagnosis were identified. Baseline demographics and liver biochemistries at diagnosis and 1 year were collected. Clinical endpoints studied included the presence of varices, variceal bleeding, ascites, HE, and liver transplant. In collaboration with HistoIndex, unstained slides underwent SHG/artificial intelligence analysis to map fibrosis according to 10 quantitative fibrosis parameters based on tissue location, including total, periportal, perisinusoidal, and pericentral area and length of strings. RESULTS Sixty-three patients with AIH (51%), primary sclerosing cholangitis (30%), or autoimmune sclerosing cholangitis (19%) at a median of 14 years old (range: 3-24) were included. An unsupervised analysis of quantitative fibrosis parameters representing total and portal fibrosis identified a patient cluster with more primary sclerosing cholangitis/autoimmune sclerosing cholangitis. This group had more fibrosis at diagnosis by METAVIR classification of histopathological review of biopsies (2.5 vs. 2; p = 0.006). This quantitative fibrosis pattern also predicted abnormal 12-month ALT with an OR of 3.6 (1.3-10, p = 0.014), liver complications with an HR of 3.2 (1.3-7.9, p = 0.01), and liver transplantation with an HR of 20.1 (3-135.7, p = 0.002). CONCLUSIONS The application of SHG/artificial intelligence algorithms in pediatric-onset AILD provides improved insight into liver histopathology through fibrosis mapping. SHG allows objective identification of patients with biliary tract involvement, which may be associated with a higher risk for refractory disease.
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Affiliation(s)
- Leticia Khendek
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
- Center for Autoimmune Liver Disease (CALD), Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
| | - Cyd Castro-Rojas
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
- Center for Autoimmune Liver Disease (CALD), Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
| | - Constance Nelson
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
- Center for Autoimmune Liver Disease (CALD), Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
| | - Mosab Alquraish
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
- Center for Autoimmune Liver Disease (CALD), Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
| | - Rebekah Karns
- Center for Autoimmune Liver Disease (CALD), Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
- Department of Pediatrics, Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
| | - Jennifer Kasten
- Department of Pediatrics, Division of Pathology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
| | - Xiao Teng
- HistoIndex Pte Ltd, Singapore, Singapore
| | - Alexander G. Miethke
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
- Center for Autoimmune Liver Disease (CALD), Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Amy E. Taylor
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
- Center for Autoimmune Liver Disease (CALD), Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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Jayabalan D, Huang Y, Calzadilla-Bertot L, Janjua M, de Boer B, Joseph J, Cheng W, Hazeldine S, Smith BW, MacQuillan GC, Wallace MC, Garas G, Adams LA, Jeffrey GP. Predictors of survival in autoimmune liver disease overlap syndromes. World J Hepatol 2024; 16:1269-1277. [PMID: 39351512 PMCID: PMC11438591 DOI: 10.4254/wjh.v16.i9.1269] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 06/16/2024] [Accepted: 06/27/2024] [Indexed: 09/23/2024] Open
Abstract
BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes (AILDOS) compared to those with single autoimmune liver disease is unclear. AIM To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death. METHODS Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap (AIH-PBC) or autoimmune hepatitis and primary sclerosing cholangitis overlap (AIH-PSC) and were identified from three tertiary centres for this cohort study. Liver-related death or transplantation (liver-related mortality) was determined using a population-based data linkage system. Prognostic scores for liver-related death were compared for accuracy [including liver outcome score (LOS), Hepascore, Mayo Score, model for end-stage liver disease (MELD) score and MELD incorporated with serum sodium (MELD-Na) score]. RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years (range, 0.35-7.7). Fourteen were female, the median age was 46.7 years (range, 17.8 to 82.1) and median Hepascore was 1 (range, 0.07-1). At five years post enrolment, 57% of patients remained free from liver-related mortality (74% AIH-PBC, 27% AIH-PSC). There was no significant difference in survival between AIH-PBC and AIH-PSC. LOS was a significant predictor of liver-related mortality (P < 0.05) in patients with AIH-PBC (n = 14) but not AIH-PSC (n = 8). A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients (P = 0.012, log-rank test, 100% sensitivity, 77.8% specificity) (Harrell's C-statistic 0.867). The MELD score, MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group. CONCLUSION Survival in the rare, AILDOS is unclear. The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients. Further trials investigating predictors of survival in AILDOS are required.
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Affiliation(s)
- Dujinthan Jayabalan
- Medical School, University of Western Australia, Nedlands 6009, Western Australia, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia.
| | - Yi Huang
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia
| | - Luis Calzadilla-Bertot
- Medical School, University of Western Australia, Nedlands 6009, Western Australia, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia
| | - Malik Janjua
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia
| | - Bastiaan de Boer
- Department of Anatomical Pathology, PathWest Laboratory Medicine, Nedlands 6009, Western Australia, Australia
| | - John Joseph
- Department of Anatomical Pathology, PathWest Laboratory Medicine, Nedlands 6009, Western Australia, Australia
| | - Wendy Cheng
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth 6000, Western Australia, Australia
| | - Simon Hazeldine
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch 6150, Western Australia, Australia
| | - Briohny W Smith
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia
| | - Gerry C MacQuillan
- Medical School, University of Western Australia, Nedlands 6009, Western Australia, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia
| | - Michael C Wallace
- Medical School, University of Western Australia, Nedlands 6009, Western Australia, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia
| | - George Garas
- Medical School, University of Western Australia, Nedlands 6009, Western Australia, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia
| | - Leon A Adams
- Medical School, University of Western Australia, Nedlands 6009, Western Australia, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia
| | - Gary P Jeffrey
- Medical School, University of Western Australia, Nedlands 6009, Western Australia, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia
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8
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Nejad SEM, Heiat M, Javanbakht M, Alavian SM, Haris MAA. Evaluation of autoimmune liver disease natural history in patients referred to Middle East Liver Diseases (MELD) center. BMC Gastroenterol 2024; 24:17. [PMID: 38178070 PMCID: PMC10768354 DOI: 10.1186/s12876-023-03105-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Accepted: 12/19/2023] [Indexed: 01/06/2024] Open
Abstract
BACKGROUND Autoimmune liver diseases (AILD) are increasing and common forms of chronic liver disease (CLD) with different clinical responses and characteristics which can result in cirrhosis. This study aimed to investigate the natural history and characteristics of AILD in an Iranian population. METHODS Patients with AILD [Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and Overlap Syndrome (OS)] referred to Middle East Liver Diseases (MELD) center, Tehran, Iran, between January 2002 and December 2022 were included in this retrospective cohort study. The main features of natural history (the trends of liver functional tests (LFT), Auto-Antibodies, response to treatment and cirrhotic status) along with demographic data were studied. RESULTS Two hundred sixty-five patients (160 (60.4%) AIH, 37 (14.0%) PBC, 20 (7.5%) PSC, 48 (18.1%) overlap syndrome) with a median follow-up time of 5 years (IQR 4 to 8 years) were included. Baseline laboratory tests revealed that patients with AIH exhibit elevated transaminase levels. However, patients suffering from PBC and PSC displayed increased alkaline phosphatase levels. Conversely, in overlap syndrome patients, both transaminases and alkaline phosphatase were observed at high levels. Autoantibodies represented themselves as important diagnostic markers for the AIH and PBC but not for PSC. The complete response occurred in 112 (70%) of and 28 (58.4%) patients with AIH and overlap syndrome respectively and 21 patients 11 (6.9%) of AIH and 10 (20.8%) of overlap syndrome) were non-responders. Other patients in these two categories were considered as insufficient responders. On the other side, 32 (91.9%) and 8 (40%) of patients with PBC and PSC biochemically responded to Ursodeoxycholic Acid (UDCA). Unpredictably, cirrhosis regression was observed in some AIH and PBC patients. CONCLUSION Appropriate medication management for AILD patients may leads to regression from cirrhosis and improvement of manifestations; while discontinuation of medication may cause relapses. However, patient suffering from PSC showed limited response to treatment.
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Affiliation(s)
- Seyed Erfan Mehdi Nejad
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mohammad Heiat
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mohammad Javanbakht
- Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Ali Abyazi Haris
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Fiske HW, Saeed F, Ward C, Sinayuk B, Ulici V, Curry M, Feller E, Shah SA. Coexisting Primary Sclerosing Cholangitis and Autoimmune Hepatitis: Overlapping Challenges in Diagnosis and Treatment. Case Rep Gastroenterol 2024; 18:167-175. [PMID: 38532799 PMCID: PMC10965232 DOI: 10.1159/000537798] [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: 08/08/2023] [Accepted: 02/10/2024] [Indexed: 03/28/2024] Open
Abstract
Introduction Hepatobiliary overlap syndromes describe the coinciding presentation of more than one immune-mediated biliary and liver disease in a single patient and present complex challenges in diagnosis and treatment. We report a case of ulcerative colitis with primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome responsive to vancomycin. Case Presentation The patient is a 30-year-old female with known ulcerative pancolitis and autoimmune hepatitis. She presented to the emergency department with a constellation of gastrointestinal symptoms, including diffuse lower abdominal pain, bloody diarrhea, and nausea with bilious vomiting. Subsequent imaging revealed the additional diagnosis of primary sclerosing cholangitis, and she was diagnosed with overlap syndrome. Multiple treatment regimens were trialed with minimal improvement. She eventually achieved normalization of both clinical status and biochemical markers after the addition of vancomycin. Conclusion Vancomycin is an underutilized therapy; its potential role in primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome has not been previously reported.
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Affiliation(s)
- Hannah W. Fiske
- Department of Internal Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Firrah Saeed
- Division of Gastroenterology, NYU Grossman School of Medicine, New York, NY, USA
| | - Christopher Ward
- Division of Gastroenterology, Lahey Hospital and Medical Center, Burlington, MA, USA
| | - Boris Sinayuk
- Department of Radiology, Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Veronica Ulici
- Department of Pathology, Mayo Clinic, Rochester, MN, USA
| | - Michael Curry
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Edward Feller
- Division of Medical Education, Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Samir A. Shah
- Division of Gastroenterology, Warren Alpert Medical School, Gastroenterology Associates Inc, Brown University, Providence, RI, USA
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10
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of autoimmune hepatitis 2022. Clin Mol Hepatol 2023; 29:542-592. [PMID: 37137334 PMCID: PMC10366804 DOI: 10.3350/cmh.2023.0087] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/27/2023] [Accepted: 04/03/2023] [Indexed: 05/05/2023] Open
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11
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Lee DU, Ponder R, Lee K, Menegas S, Fan GH, Chou H, Jung D, Lee K, Hastie DJ, Urrunaga NH. The differences in post-liver transplant outcomes of patients with autoimmune hepatitis who present with overlapping autoimmune liver diseases. Hepatol Int 2023; 17:720-734. [PMID: 36575337 PMCID: PMC10225314 DOI: 10.1007/s12072-022-10468-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 12/03/2022] [Indexed: 12/28/2022]
Abstract
BACKGROUND Patients with autoimmune hepatitis (AIH) may co-present with features of primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). Using a national transplant registry, the outcomes of patients with these autoimmune liver conditions were compared. METHODS The UNOS-STAR registry was used to select a study population of AIH, PSC, and PBC liver transplant (LT) patients. Living and multi-organ transplant cases were excluded. Using the UNOS-registered diagnoses, the study population was subdivided into those with nonoverlapping autoimmune liver diseases and those with overlapping forms (e.g., AIH-PBC). Outcomes were compared, using endpoints such as all-cause mortality, graft failure, and organ-system specific causes of death. RESULTS The main analysis featured 2048 entries, with 1927 entries having nonoverlapping AIH, 52 entries having PSC overlap, and 69 entries having PBC overlap. Patients with PBC overlap were more likely to have graft failure (adjusted hazard ratio [aHR] 3.46 95% CI 1.70-7.05), mortality secondary to respiratory causes (aHR 3.57 95% CI 1.23-10.43), and mortality secondary to recurrent disease (aHR 9.53 95% CI 1.85-49.09). Case incidence rates reflected these findings, expressed in events per 1000 person-years. For patients with PBC overlap and nonoverlapping AIH cases, respectively. Graft failure: 28.87 events vs. 9.42 events, mortality secondary to respiratory causes: 12.83 deaths vs. 3.77 deaths, mortality secondary to recurrent disease: 6.42 deaths vs. 1.26 deaths. Those with AIH-PSC overlap experienced a higher risk of death from graft infection (aHR 10.43 95% CI 1.08-100.37; case-incidence rate: 3.89 vs. 0.31 mortalities per 1000 person-years). Supplementary analysis showed similar findings, in which overlapping autoimmune conditions were associated with higher adverse outcome rates. CONCLUSION Patients with AIH-PBC overlap have higher risk of mortality due to recurrent liver disease and respiratory causes, and patients with AIH-PSC overlap have higher risk of mortality due to graft infection. While further prospective studies are needed to clarify the underlying mechanisms related to these findings, our study characterizes the prognostic implications of AIH overlap on post-LT mortality and graft failure risks.
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Affiliation(s)
- David Uihwan Lee
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, 22 S. Greene St N3W50, Baltimore, MD, 21201, USA.
| | - Reid Ponder
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - Kijung Lee
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - Samantha Menegas
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, 22 S. Greene St N3W50, Baltimore, MD, 21201, USA
| | - Gregory Hongyuan Fan
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - Harrison Chou
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - Daniel Jung
- Department of Medicine, University of Missouri-Kansas City School of Medicine, Boston, MA, USA
| | - Keeseok Lee
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - David Jeffrey Hastie
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - Nathalie Helen Urrunaga
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, 22 S. Greene St N3W50, Baltimore, MD, 21201, USA
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12
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Ricciuto A, Kamath BM, Hirschfield GM, Trivedi PJ. Primary sclerosing cholangitis and overlap features of autoimmune hepatitis: a coming of age or an age-ist problem? J Hepatol 2023:S0168-8278(23)00162-9. [PMID: 36870613 DOI: 10.1016/j.jhep.2023.02.030] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 02/15/2023] [Accepted: 02/18/2023] [Indexed: 03/06/2023]
Abstract
Autoimmune liver diseases are siloed into three syndromes that define clinical practice. These classifiers can, and are, challenged by variant presentations across all ages, something inevitable to disease definitions that rely on interpreting inherently variable semi-quantitative/qualitative clinical, laboratory, pathological or radiological findings. Furthermore this remains premised by an ongoing absence of definable disease aetiologies. Clinicians thus encounter individuals with biochemical, serological, and histological manifestations that are common to both primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH), often labelled as 'PSC/AIH-overlap'. In childhood the term 'autoimmune sclerosing cholangitis (ASC)' may be used, and some propose this to be a distinct disease process. In this article we champion the concept that ASC and PSC/AIH-overlap are not distinct entities. Rather, they represent inflammatory phases of PSC frequently manifesting earlier in disease course, most notably in younger patients. Ultimately, disease outcome remains that of a more classical PSC phenotype observed in later life. Thus, we argue that it is now time to align disease names and descriptions used by clinicians across all patient subpopulations, to help care become uniform and ageless. This will enhance collaborative studies and contribute ultimately to rational treatment advances.
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Affiliation(s)
- Amanda Ricciuto
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Binita M Kamath
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Ontario, Canada
| | - Palak J Trivedi
- National Institute for Health and Care 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.
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13
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Taneja S, Mehtani R, De A, Mitra S, Rathi S, Verma N, Premkumar M, Minz R, Duseja A, Das A, Singh V, Dhiman RK, Chawla YK. Spectrum of Autoimmune Liver Disease and Real-World Treatment Experience from a Tertiary Care Hospital. J Clin Exp Hepatol 2023; 13:241-251. [PMID: 36950480 PMCID: PMC10025584 DOI: 10.1016/j.jceh.2022.11.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 11/01/2022] [Indexed: 11/12/2022] Open
Abstract
Background and aims Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India. Methods A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC. Results Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000-1.003], P = 0.034), high albumin (OR 1.91 [1.05-3.48], P = 0.034) and low fibrosis on biopsy (OR 0.54 [0.33-0.91], P = 0.020) predicted complete response. Conclusion AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response.
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Key Words
- ACLF, acute-on-chronic liver failure
- AIH, autoimmune hepatitis
- AILD, Autoimmune liver diseases
- ALF, acute liver failure
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- AMA, anti-mitochondrial antibody
- ASMA, anti-smooth muscle antibody
- AST, aspartate aminotransferase
- ELISA, enzyme-linked immunosorbent assay
- IBD, inflammatory bowel disease
- INR, international normalized ratio
- IgG, immunoglobulin G
- LC-1, liver cytosol 1
- LKM-1, liver kidney microsomal 1
- LSM, liver stiffness measurement
- LT, liver transplant
- MMF, mycophenolate mofetil
- MRCP, magnetic resonance cholangiopancreatography
- PBC, primary biliary cholangitis
- PSC, primary sclerosing cholangitis
- SLA, soluble liver antigen
- UDCA, ursodeoxycholic acid
- ULN, upper limit of normal
- autoimmune hepatitis
- cirrhosis
- overlap syndromes
- primary biliary cholangitis
- primary sclerosing cholangitis
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Affiliation(s)
- Sunil Taneja
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Rohit Mehtani
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Arka De
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Suvradeep Mitra
- Department of Immunopathology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Sahaj Rathi
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Nipun Verma
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Ranjana Minz
- Department of Immunopathology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Ashim Das
- Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Virendra Singh
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Radha K. Dhiman
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Yogesh K. Chawla
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
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14
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Kim JK. [Treatment of Autoimmune Hepatitis]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 81:72-85. [PMID: 36824035 DOI: 10.4166/kjg.2023.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/13/2023] [Accepted: 02/13/2023] [Indexed: 02/25/2023]
Abstract
Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by elevated levels of transaminases, immunoglobulin G, and positive autoantibodies. The disease course is dynamic and presents heterogeneous disease manifestations at diagnosis. This review summarizes the issues regarding the treatment and monitoring of AIH in adult patients. Glucocorticoids and azathioprine are the first line of treatment. Alternative first-line treatments include budesonide or mycophenolate mofetil (MMF). Although no randomized controlled trials have been performed, MMF, cyclosporine, tacrolimus, 6-mercaptopurine, 6-thioguanine, allopurinol, sirolimus, everolimus, infliximab, or rituximab have been attempted in patients not responding to or intolerant to first-line treatments. Most patients require life-long special monitoring, with or without maintenance treatment.
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Affiliation(s)
- Ja Kyung Kim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
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15
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Bowlus CL, Arrivé L, Bergquist A, Deneau M, Forman L, Ilyas SI, Lunsford KE, Martinez M, Sapisochin G, Shroff R, Tabibian JH, Assis DN. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2023; 77:659-702. [PMID: 36083140 DOI: 10.1002/hep.32771] [Citation(s) in RCA: 141] [Impact Index Per Article: 70.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/26/2022] [Indexed: 01/28/2023]
Affiliation(s)
- Christopher L Bowlus
- Division of Gastroenterology , University of California Davis Health , Sacramento , California , USA
| | | | - Annika Bergquist
- Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden
| | - Mark Deneau
- University of Utah , Salt Lake City , Utah , USA
| | - Lisa Forman
- University of Colorado , Aurora , Colorado , USA
| | - Sumera I Ilyas
- Mayo Clinic College of Medicine and Science , Rochester , Minnesota , USA
| | - Keri E Lunsford
- Rutgers University-New Jersey Medical School , Newark , New Jersey , USA
| | - Mercedes Martinez
- Vagelos College of Physicians and Surgeons , Columbia University , New York , New York , USA
| | | | | | - James H Tabibian
- David Geffen School of Medicine at UCLA , Los Angeles , California , USA
| | - David N Assis
- Yale School of Medicine , New Haven , Connecticut , USA
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16
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Morgan MA, Khot R, Sundaram KM, Ludwig DR, Nair RT, Mittal PK, Ganeshan DM, Venkatesh SK. Primary sclerosing cholangitis: review for radiologists. Abdom Radiol (NY) 2023; 48:136-150. [PMID: 36063181 PMCID: PMC9852001 DOI: 10.1007/s00261-022-03655-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/13/2022] [Accepted: 08/15/2022] [Indexed: 01/22/2023]
Abstract
Primary sclerosing cholangitis is a rare chronic inflammatory disease affecting the bile ducts, which can eventually result in bile duct strictures, cholestasis and cirrhosis. Patients are often asymptomatic but may present with clinical features of cholestasis. Imaging plays an important role in the diagnosis and management. This review covers the pathophysiology, clinical features, imaging findings as well as methods of surveillance and post-transplant appearance.
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Affiliation(s)
- Matthew A Morgan
- Department of Radiology, University of Pennsylvania Health System, 1 Silverstein, 3400 Spruce Street, Philadelphia, PA, USA.
| | - Rachita Khot
- Radiology and Medical Imaging, University of Virginia Health, 1215 Lee Street, Charlottesville, VA, USA
| | - Karthik M Sundaram
- Department of Radiology, University of Pennsylvania Health System, 1 Silverstein, 3400 Spruce Street, Philadelphia, PA, USA
| | - Daniel R Ludwig
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, Campus Box 8131, Saint Louis, MO, USA
| | - Rashmi T Nair
- Department of Radiology, University of Kentucky, 800 Rose Street, Room HX 313B, Lexington, KY, 40536-0293, USA
| | - Pardeep K Mittal
- Medical College of Georgia at Augusta University, 1120 15th street BA -1411, Augusta, GA, 30912, USA
| | - Dhakshina M Ganeshan
- The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Unit 1473, Houston, TX, 77030, USA
| | - Sudhakar K Venkatesh
- Abdominal Imaging, Department of Radiology, Mayo Clinic, Rochester, MN, 55905, USA
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17
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Suzuki T, Naitoh I, Katano T, Matsuura K, Nagura Y, Fujiwara K, Nojiri S, Kataoka H. Primary Sclerosing Cholangitis and Autoimmune Hepatitis Overlapping Syndrome Complicated by Ulcerative Colitis. Intern Med 2022; 61:2471-2475. [PMID: 35110488 PMCID: PMC9449607 DOI: 10.2169/internalmedicine.8866-21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 12/12/2021] [Indexed: 01/01/2023] Open
Abstract
The case of a 28-year-old man who had primary sclerosing cholangitis and autoimmune hepatitis overlapping syndrome (PSC-AIH OS) complicated by ulcerative colitis (UC) is reported. First, he was diagnosed with PSC complicated by UC and initially treated with ursodeoxycholic acid and mesalazine. Twenty-four months later, liver damage reappeared, and we performed a liver biopsy, which showed the features of AIH. We eventually diagnosed him with PSC-AIH OS complicated by UC. If liver damage worsens in PSC patients, PSC-AIH OS should be considered. The optimum management approach for PSC-AIH OS should be established.
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Affiliation(s)
- Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Takahito Katano
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Yoshihito Nagura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Shunsuke Nojiri
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
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18
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Gender and Autoimmune Liver Diseases: Relevant Aspects in Clinical Practice. J Pers Med 2022; 12:jpm12060925. [PMID: 35743710 PMCID: PMC9225254 DOI: 10.3390/jpm12060925] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 05/25/2022] [Accepted: 05/28/2022] [Indexed: 12/12/2022] Open
Abstract
Autoimmune liver diseases (AILDs) include autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. The etiologies of AILD are not well understood but appear to involve a combination of genetic and environmental factors. AILDs commonly affect young individuals and are characterized by a highly variable clinical course. These diseases significantly influence quality of life and can progress toward liver decompensation or the onset of hepatocellular or cholangiocarcinoma; a significant number of patients eventually progress to end-stage liver disease, requiring liver transplantation. In this review, we focus on the sex characteristics and peculiarities of AILD patients and highlight the relevance of a sex-specific analysis in future studies. Understanding the sex differences underlying AILD immune dysregulation may be critical for developing more effective treatments.
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19
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New agents for immunosuppression. Best Pract Res Clin Gastroenterol 2021; 54-55:101763. [PMID: 34874846 DOI: 10.1016/j.bpg.2021.101763] [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: 07/19/2021] [Revised: 08/16/2021] [Accepted: 08/30/2021] [Indexed: 01/31/2023]
Abstract
The human abdomen harbors organs that the host's immune system can attack easily. This immunological storm front leads to diseases like Crohn's Disease, Ulcerative Colitis or Autoimmune Hepatitis. Serious symptoms like pain, diarrhea, fatigue, or malnutrition accompany these diseases. Moreover, many patients have an increased risk for developing special kind of malignancies and some autoimmune disease can show a high mortality. The key to treat them consists of a deep understanding of their pathophysiology. In vitro and especially in vivo basic research laid the foundation for our increasing knowledge about it during the past years. This enabled the development of new therapeutic approaches that interact directly with cytokines or immune cells instead of building the treatment on a total immunosuppression. Different kind of antibodies, kinase inhibitors, and regulatory T cells build the base for these approaches. This review shows new therapeutical approaches in gastrointestinal autoimmune diseases in context to their pathophysiological basis.
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20
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Abstract
Cholestatic liver disease is a disease that causes liver damage and fibrosis owing to bile stasis. It is represented by primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), but the pathophysiological pathways that cause bile stasis in both diseases are different. The pathogenesis of the disease is still unclear, although autoimmune mechanisms have been postulated and partially elucidated. Although the disease may progress slowly with only mild liver dysfunction, it may progress to liver cirrhosis or liver failure, which require liver transplantation. As a medical treatment, ursodeoxycholic acid is widely used for PBC and has proved to be very effective against disease progression in cases of PBC. On the other hand, its efficacy is limited in cases of PSC, and the research and development of various drugs are underway. Furthermore, the clinical course of both diseases is quite variable, making the design of clinical trials fairly difficult. In this review, we present the general natural history of PBC and PSC, and provide information on the latest drug therapies currently available and those that are under investigation.
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21
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Rabiee A, Silveira MG. Primary sclerosing cholangitis. Transl Gastroenterol Hepatol 2021; 6:29. [PMID: 33824933 DOI: 10.21037/tgh-20-266] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 10/19/2020] [Indexed: 12/15/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis, and often requires liver transplantation (LT). PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40. Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC. PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD. When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue. The etiology of PSC is poorly understood, but an increasing body of evidence supports the concept of cholangiocyte injury as a result of environmental exposure and an abnormal immune response in genetically susceptible individuals. PSC is a progressive disease, yet no effective medical therapy for halting disease progression has been identified. Management of PSC is mainly focused on treatment of symptoms and addressing complications. PSC can be complicated by bacterial cholangitis, dominant strictures (DSs), gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy. CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC. LT is currently the only life-extending therapeutic approach for eligible patients with end-stage PSC, ultimately required in approximately 40% of patients. LT secondary to PSC has an excellent outcome compared to other LT indications, although the disease can recur and result in morbidity post-transplant.
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Affiliation(s)
- Anahita Rabiee
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - Marina G Silveira
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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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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Chung Y, Rahim MN, Graham JJ, Zen Y, Heneghan MA. An update on the pharmacological management of autoimmune hepatitis. Expert Opin Pharmacother 2021; 22:1475-1488. [PMID: 33624559 DOI: 10.1080/14656566.2021.1895747] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Introduction: Autoimmune hepatitis (AIH) is an immune mediated, inflammatory disease affecting the liver as a result of environmental triggers in susceptible individuals leading to loss of self-tolerance. The immunopathogenesis of AIH is not fully understood, which limits targeted therapeutic options.Areas covered: In this review, the authors provide an overview of current practice in the management of AIH, which include induction therapy with corticosteroids (± thiopurines), followed by maintenance therapy. Lack of early response to treatment may serve as a predictor of those at risk of requiring treatment escalation to second- and third-line agents such as mycophenolate mofetil (MMF), calcineurin inhibitors or biologics. Evidence for third-line agents from small retrospective studies or individual centers are reviewed. The nuances of AIH treatment in pregnancy, overlap syndromes, and drug induced liver injury (DILI) warrant further consideration.Expert opinion: Augmenting the balance of regulatory T cells (Treg) and effector T cells is an appealing therapeutic target with a multitude of agents in development. Many of the challenges in AIH research are due to its rarity and lack of randomized data. Management of AIH should strive towards individualized care through risk stratification and use of the best therapeutic modality for each patient.
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Affiliation(s)
- Yooyun Chung
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London, United Kingdom
| | - Mussarat N Rahim
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London, United Kingdom
| | - Jonathon J Graham
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London, United Kingdom
| | - Yoh Zen
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London, United Kingdom
| | - Michael A Heneghan
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London, United Kingdom
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24
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Ballotin VR, Bigarella LG, Riva F, Onzi G, Balbinot RA, Balbinot SS, Soldera J. Primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome associated with inflammatory bowel disease: A case report and systematic review. World J Clin Cases 2020; 8:4075-4093. [PMID: 33024765 PMCID: PMC7520795 DOI: 10.12998/wjcc.v8.i18.4075] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 04/23/2020] [Accepted: 07/30/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND A previously healthy 22-year-old woman presented with abdominal pain and jaundice. She had a reagent antinuclear factor (1:640, with a homogeneous nuclear pattern) and hypergammaglobulinemia (2.16 g/dL). Anti-smooth muscle, anti-mitochondrial and anti-liver-kidney microsomal antibody type 1 antibodies were negative. Magnetic resonance cholangiography showed a cirrhotic liver with multiple focal areas of strictures of the intrahepatic bile ducts, with associated dilations. Liver biopsy demonstrated periportal necroinflammatory activity, plasmocyte infiltration and advanced fibrosis. Colonoscopy showed ulcerative pancolitis and mild activity (Mayo score 1), with a spared rectum. Treatment with corticosteroids, azathioprine, ursodeoxycholic acid and mesalamine was initiated, with improvement in laboratory tests. The patient was referred for a liver transplantation evaluation. AIM To report the case of a female patient with autoimmune hepatitis and primary sclerosing cholangitis (PSC) overlap syndrome associated with ulcerative colitis and to systematically review the available cases of autoimmune hepatitis and PSC overlap syndrome. METHODS In accordance with preferred reporting items for systematic reviews and meta-analysis protocols guidelines, retrieval of studies was based on medical subject headings and health sciences descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), Biblioteca Regional de Medicina, Latin American and Caribbean Health Sciences Literature, Cochrane Library for Systematic Reviews and Opengray.eu. Languages were restricted to English, Spanish and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually. RESULTS The search strategy retrieved 3349 references. In the final analysis, 44 references were included, with a total of 109 cases reported. The most common clinical finding was jaundice and 43.5% of cases were associated with inflammatory bowel disease. Of these, 27.6% were cases of Crohn's disease, 68% of ulcerative colitis, and 6.4% of indeterminate colitis. Most patients were treated with steroids. All-cause mortality was 3.7%. CONCLUSION PSC and autoimmune hepatitis overlap syndrome is generally associated with inflammatory bowel disease and has low mortality and good response to treatment.
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Affiliation(s)
| | | | - Floriano Riva
- CPM Laboratório de Caxias do Sul, Caxias do Sul 95070561, Brazil
| | - Georgia Onzi
- Clinical Gastroenterology, Universidade de Caxias do Sul (UCS), Caxias do Sul 95070560, Brazil
| | - Raul Angelo Balbinot
- Clinical Gastroenterology, Universidade de Caxias do Sul (UCS), Caxias do Sul 95070560, Brazil
| | | | - Jonathan Soldera
- Clinical Gastroenterology, Universidade de Caxias do Sul (UCS), Caxias do Sul 95070560, Brazil
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25
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Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, Vierling JM, Alsawas M, Murad MH, Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology 2020; 72:671-722. [PMID: 31863477 DOI: 10.1002/hep.31065] [Citation(s) in RCA: 548] [Impact Index Per Article: 109.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 11/25/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Cara L Mack
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - David Adams
- Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - David N Assis
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Nanda Kerkar
- Golisano Children's Hospital at Strong, University of Rochester Medical Center, New York, NY
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Marlyn J Mayo
- Division of Digestive and Liver Diseases, University of Texas SW Medical Center, Dallas, TX
| | - John M Vierling
- Medicine and Surgery, Baylor College of Medicine, Houston, TX
| | | | - Mohammad H Murad
- Mayo Knowledge and Encounter Research Unit, Mayo Clinic College of Medicine, Rochester, MN
| | - Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
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26
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Freedman BL, Danford CJ, Patwardhan V, Bonder A. Treatment of Overlap Syndromes in Autoimmune Liver Disease: A Systematic Review and Meta-Analysis. J Clin Med 2020; 9:jcm9051449. [PMID: 32414025 PMCID: PMC7291241 DOI: 10.3390/jcm9051449] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 04/30/2020] [Accepted: 05/07/2020] [Indexed: 12/13/2022] Open
Abstract
The treatment of overlap syndromes is guided by small observational studies whose data have never been synthesized in a rigorous, quantitative manner. We conducted a systematic review and meta-analysis to evaluate the efficacy of available treatments for these rare and morbid conditions. We searched the literature for studies comparing ≥2 therapies for autoimmune hepatitis (AIH)-primary biliary cholangitis (PBC), AIH-primary sclerosing cholangitis (PSC), PBC-PSC, AIH-PBC-PSC, autoimmune cholangitis (AIC), or autoimmune sclerosing cholangitis (ASC) with respect to various clinical outcomes, including biochemical improvement and transplant-free survival. A total of 28 studies met the inclusion criteria for AIH-PBC, AIH-PSC, AIC, and ASC. AIH-PBC patients tended to experience more biochemical improvement with ursodeoxycholic acid (UDCA) + [corticosteroids and/or antimetabolites], i.e., "combination therapy", than with corticosteroids ± azathioprine (RR = 4.00, 95% CI 0.93-17.18). AIH-PBC patients had higher transplant-free survival with combination therapy than with UDCA, but only when studies with follow-up periods ≤90 months were excluded (RR = 6.50, 95% CI 1.47-28.83). Combination therapy may therefore be superior to both UDCA and corticosteroids ± azathioprine for the treatment of AIH-PBC, but additional studies are needed to show this definitively and to elucidate optimal treatments for other overlap syndromes.
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Affiliation(s)
- Benjamin L. Freedman
- Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA;
| | - Christopher J. Danford
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Dana 603, Boston, MA 02215, USA;
| | - Vilas Patwardhan
- Liver Center, Autoimmune and Cholestatic Liver Disease Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St. Suite 8E, Boston, MA 02215, USA;
| | - Alan Bonder
- Liver Center, Autoimmune and Cholestatic Liver Disease Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St. Suite 8E, Boston, MA 02215, USA;
- Correspondence: ; Tel.: +1-617-632-1070
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27
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Prognostic factors for remission, relapse, and treatment complications in type 1 autoimmune hepatitis. Heliyon 2020; 6:e03767. [PMID: 32382677 PMCID: PMC7203077 DOI: 10.1016/j.heliyon.2020.e03767] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 02/22/2020] [Accepted: 04/06/2020] [Indexed: 02/07/2023] Open
Abstract
Background and aim Autoimmune hepatitis (AIH) is a rare chronic form of hepatitis, the prognosis for which has not been definitively established. The current study aimed to define the prognostic factors for remission and compare the median time to remission, complications, and relapse rate between type 1 AIH patients treated with prednisolone monotherapy and those treated using prednisolone in combination with azathioprine. Materials and methods The data of 86 patients diagnosed with type 1 AIH between January 1998 and January 2018 were retrospectively reviewed. Clinical, serological, and histological parameters were obtained. Cox-proportional hazard and logistic regression analyses were applied to the data. Results The prognostic factors related to complete remission were absence of liver cirrhosis, hypertension, and azathioprine exposure. The median time to complete remission of the prednisolone group (92 days; 95%CI; 65–264 days) was significantly shorter (P = 0.01) than that of the combination group (336 days; 95%CI; 161–562 days); however, the prednisolone group had higher rates of treatment complications—including skin and soft tissue infections (P = 0.010) and cushingoid appearance (P = 0.011)—than the combination group. The prednisolone group also had a higher relapse rate (odds ratio 6.13, 95% CI 1.72–21.80, P = 0.005). Conclusions The absence of liver cirrhosis and hypertension at the time of diagnosis and no azathioprine exposure during the treatment period were favorable prognostic factors for complete remission. The prednisolone group had a significantly shorter median time to complete remission but higher rates of treatment complications and a higher relapse rate than the combination group.
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28
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Chayanupatkul M, Fiel MI, Schiano TD. The clinical characteristics, pre- and post-liver transplantation outcomes in patients having autoimmune overlap syndromes. Clin Transplant 2020; 34:e13841. [PMID: 32073690 DOI: 10.1111/ctr.13841] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 12/01/2019] [Accepted: 02/16/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND There are little data on the pre- and post-liver transplantation (LT) outcomes of patients having autoimmune hepatitis-primary biliary cholangitis (AIH-PBC), AIH-primary sclerosing cholangitis (AIH-PSC), and AIH-small-duct PSC (AIH-SDPSC). The aim of this study was to analyze pre- and post-LT outcomes and survival of patients having different overlap syndromes (OS) undergoing LT. METHODS Patients with compatible clinical and pathologic features of AIH-PBC (n = 86), AIH-PSC (n = 22), and AIH-SDPSC (n = 9) were included in the study. Demographic, laboratory, clinical, and survival data were analyzed. Multivariable analyses were performed to determine factors predicting transplant-free survival. RESULTS AIH-primary sclerosing cholangitis patients were less treatment-responsive and were more likely to undergo LT than other OS. No survival difference was noted among the 3 groups. Liver decompensation was independently associated with higher mortality (HR 21.78; 95% CI 2.50-190.01). Thirteen patients with OS underwent LT. One-year survival post-LT was 91.7%. Overall recurrence rate for OS post-LT was 8%. CONCLUSIONS AIH-primary sclerosing cholangitis patients were more likely to require LT compared with patients having AIH-PBC. Transplant-free survival was similar among the three AIH-overlap syndromes. Allograft recurrence of OS occurred in about 10% of cases. Patients with OS appear to have good short- and medium-term post-LT outcomes in terms of graft function and overall survival.
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Affiliation(s)
- Maneerat Chayanupatkul
- Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.,Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Recanati-Miller Transplantation Institute, New York, NY, USA
| | - Maria Isabel Fiel
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Thomas D Schiano
- Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Recanati-Miller Transplantation Institute, New York, NY, USA
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29
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Umetsu S, Notohara K, Nakazawa T, Tsunoda T, Sogo T, Komatsu H, Tanaka A, Tazuma S, Takikawa H, Inui A, Fujisawa T. Long-term outcomes of pediatric-onset primary sclerosing cholangitis: A single-center experience in Japan. Hepatol Res 2019; 49:1386-1397. [PMID: 31408920 DOI: 10.1111/hepr.13421] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 07/27/2019] [Accepted: 08/05/2019] [Indexed: 01/11/2023]
Abstract
AIM Primary sclerosing cholangitis (PSC) is very rare in Japan. Although a large-scale cohort study of 781 pediatric-onset PSC patients in Europe and North America showed that the 5-year survival with native liver was 88%, the long-term outcomes of pediatric-onset PSC in Japan are unknown. Here, we evaluated the clinical outcomes of pediatric-onset PSC in Japan. METHODS We carried out a retrospective cohort study with a medical records review of pediatric PSC patients diagnosed between 1986 and 2017 at a single center. The PSC diagnoses were based on cholangiography, liver histology, and biochemical findings. The patients' survival was analyzed using the Kaplan-Meier method. Prognostic factors were determined by univariate and multivariate analyses using the Cox proportional hazards regression model. RESULTS We identified 39 pediatric-onset PSC patients (22 boys, 17 girls). The median age at diagnosis was 9 years (interquartile range 6.0-13.5 years). The median follow-up period was 5.5 years (interquartile range 3.4-8.7 years). The phenotypes of PSC-autoimmune hepatitis, PSC-inflammatory bowel disease, and small-duct PSC were diagnosed in 13 (33.3%), 36 out of 38 (94.8%), and three (7.7%) patients, respectively. The 5-year liver transplantation-free survival of the whole cohort was 93.5%. Nine patients underwent liver transplantation, and four of these nine cases resulted in death. Both the univariate and multivariate analyses showed that the phenotype of "PSC-autoimmune hepatitis overlap" was an independent poor prognostic factor. CONCLUSIONS The overall survival of pediatric-onset PSC in Japan was comparable to those in Western countries. The phenotype of PSC-autoimmune hepatitis was identified as a prognostic factor associated with a poorer long-term outcome.
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Affiliation(s)
- Shuichiro Umetsu
- Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama-shi Tobu Hospital, Yokohama, Japan.,Department of Hepatology and Gastroenterology for Growth and Health, Toho University Graduate School of Medicine, Tokyo, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Takahiro Nakazawa
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Tomoyuki Tsunoda
- Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama-shi Tobu Hospital, Yokohama, Japan
| | - Tsuyoshi Sogo
- Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama-shi Tobu Hospital, Yokohama, Japan
| | - Haruki Komatsu
- Department of Pediatrics, Toho University Sakura Hospital, Sakura, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Susumu Tazuma
- Department of General Medicine, Hiroshima University Graduate School of Medical Science, Programs of Applied Medicine, Clinical Pharmacotherapy, Hiroshima, Japan
| | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Ayano Inui
- Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama-shi Tobu Hospital, Yokohama, Japan.,Department of Hepatology and Gastroenterology for Growth and Health, Toho University Graduate School of Medicine, Tokyo, Japan
| | - Tomoo Fujisawa
- Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama-shi Tobu Hospital, Yokohama, Japan
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30
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Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D, Vierling JM, Adams D, Alpini G, Banales JM, Beuers U, Björnsson E, Bowlus C, Carbone M, Chazouillères O, Dalekos G, De Gottardi A, Harada K, Hirschfield G, Invernizzi P, Jones D, Krawitt E, Lanzavecchia A, Lian ZX, Ma X, Manns M, Mavilio D, Quigley EM, Sallusto F, Shimoda S, Strazzabosco M, Swain M, Tanaka A, Trauner M, Tsuneyama K, Zigmond E, Gershwin ME. The challenges of primary biliary cholangitis: What is new and what needs to be done. J Autoimmun 2019; 105:102328. [PMID: 31548157 DOI: 10.1016/j.jaut.2019.102328] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 08/18/2019] [Accepted: 08/20/2019] [Indexed: 02/06/2023]
Abstract
Primary Biliary Cholangitis (PBC) is an uncommon, chronic, cholangiopathy of autoimmune origin and unknown etiology characterized by positive anti-mitochondrial autoantibodies (AMA), female preponderance and progression to cirrhosis if left untreated. The diagnosis is based on AMA- or PBC-specific anti-nuclear antibody (ANA)-positivity in the presence of a cholestatic biochemical profile, histologic confirmation being mandatory only in seronegative cases. First-line treatment is ursodeoxycholic acid (UDCA), which is effective in preventing disease progression in about two thirds of the patients. The only approved second-line treatment is obeticholic acid. This article summarizes the most relevant conclusions of a meeting held in Lugano, Switzerland, from September 23rd-25th 2018, gathering basic and clinical scientists with various background from around the world to discuss the latest advances in PBC research. The meeting was dedicated to Ian Mackay, pioneer in the field of autoimmune liver diseases. The role of liver histology needs to be reconsidered: liver pathology consistent with PBC in AMA-positive individuals without biochemical cholestasis is increasingly reported, raising the question as to whether biochemical cholestasis is a reliable disease marker for both clinical practice and trials. The urgent need for new biomarkers, including more accurate markers of cholestasis, was also widely discussed during the meeting. Moreover, new insights in interactions of bile acids with biliary epithelia in PBC provide solid evidence of a role for impaired epithelial protection against potentially toxic hydrophobic bile acids, raising the fundamental question as to whether this bile acid-induced epithelial damage is the cause or the consequence of the autoimmune attack to the biliary epithelium. Strategies are needed to identify difficult-to-treat patients at an early disease stage, when new therapeutic approaches targeting immunologic pathways, in addition to bile acid-based therapies, may be effective. In conclusion, using interdisciplinary approaches, groundbreaking advances can be expected before long in respect to our understanding of the etiopathogenesis of PBC, with the ultimate aim of improving its treatment.
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Affiliation(s)
- Benedetta Terziroli Beretta-Piccoli
- Epatocentro Ticino, Lugano, Switzerland; Institute of Liver Studies, MowatLabs, King's College Hospital, London, UK; European Reference Network ERN RARE-LIVER.
| | - Giorgina Mieli-Vergani
- Paediatric Liver, GI and Nutrition Centre, MowatLabs, King's College Hospital, London, UK
| | - Diego Vergani
- Institute of Liver Studies, MowatLabs, King's College Hospital, London, UK
| | - John M Vierling
- Division of Abdominal Transplantation and Section of Gastroenterology and Hepatology, Departments of Medicine and Surgery, Baylor College of Medicine, Houston, TX, USA
| | - David Adams
- Birmingham NIHR Biomedical Research Centre, Institute of Immunology and Immunotherapy, College of Medical and Dental SciencesMedical School, University of Birmingham, Birmingham, UK
| | - Gianfranco Alpini
- Indiana Center for Liver Research, Richard L. Roudebush VA Medical Center and Indiana University, Indianapolis, IN, USA
| | - Jesus M Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), CIBERehd, Ikerbasque, San Sebastián, Spain
| | - Ulrich Beuers
- European Reference Network ERN RARE-LIVER; Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Einar Björnsson
- Division of Gastroenterology and Hepatology, Landspitali the National University Hospital of Iceland, Reykjavík, Iceland
| | - Christopher Bowlus
- Division of Gastroenterology and Hepatology, University of California at Davis School of Medicine, Davis, CA, USA
| | - Marco Carbone
- Division Gastroenterology and Center for Autoimmune Liver Diseases, University of Milan-Bicocca School of Medicine, Monza, Italy
| | - Olivier Chazouillères
- European Reference Network ERN RARE-LIVER; Service d'Hépatologie, Hôpital Saint-Antoine, Paris, France
| | - George Dalekos
- Institute of Internal Medicine and Hepatology, Department of Medicine and Research, Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa, Greece
| | - Andrea De Gottardi
- European Reference Network ERN RARE-LIVER; Epatocentro Ticino & Division of Gastroenterology and Hepatology Ente Ospedaliero Cantonale and Università della Svizzera Italiana, Lugano, Switzerland
| | - Kenichi Harada
- Department of Human Pathology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Gideon Hirschfield
- Toronto Centre for Liver Disease, University Health Network and University of Toronto, Toronto, Canada
| | - Pietro Invernizzi
- European Reference Network ERN RARE-LIVER; Division Gastroenterology and Center for Autoimmune Liver Diseases, University of Milan-Bicocca School of Medicine, Monza, Italy
| | - David Jones
- Institute of Cellular Medicine and NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK
| | - Edward Krawitt
- Department of Medicine, University of Vermont, Burlington, VT, USA
| | | | - Zhe-Xiong Lian
- Institutes for Life Sciences, South China University of Technology, Higher Education Mega Center, Guangzhou, China
| | - Xiong Ma
- Shanghai Institute of Digestive Disease, Renji Hospital, Jiao Tong University School of Medicine, Shanghai, China
| | - Michael Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), Hannover, Germany
| | - Domenico Mavilio
- Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy; Department of Medical Biotechnologies and Translational Medicine (BioMeTra), University of Milan, Italy
| | - Eamon Mm Quigley
- Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, TX, USA
| | - Federica Sallusto
- Institute for Research in Biomedicine (IRB), Bellinzona, Switzerland
| | - Shinji Shimoda
- Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Mario Strazzabosco
- Liver Center, Department of Medicine, Yale University, New Haven, CT, USA
| | - Mark Swain
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Koichi Tsuneyama
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Ehud Zigmond
- Research Center for Digestive Tract and Liver Diseases, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - M Eric Gershwin
- Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, California, USA.
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31
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Chapman MH, Thorburn D, Hirschfield GM, Webster GGJ, Rushbrook SM, Alexander G, Collier J, Dyson JK, Jones DE, Patanwala I, Thain C, Walmsley M, Pereira SP. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut 2019; 68:1356-1378. [PMID: 31154395 PMCID: PMC6691863 DOI: 10.1136/gutjnl-2018-317993] [Citation(s) in RCA: 178] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 02/21/2019] [Accepted: 03/24/2019] [Indexed: 12/11/2022]
Abstract
These guidelines on the management of primary sclerosing cholangitis (PSC) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included medical representatives from hepatology and gastroenterology groups as well as patient representatives from PSC Support. The guidelines aim to support general physicians, gastroenterologists and surgeons in managing adults with PSC or those presenting with similar cholangiopathies which may mimic PSC, such as IgG4 sclerosing cholangitis. It also acts as a reference for patients with PSC to help them understand their own management. Quality of evidence is presented using the AGREE II format. Guidance is meant to be used as a reference rather than for rigid protocol-based care as we understand that management of patients often requires individual patient-centred considerations.
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Affiliation(s)
- Michael Huw Chapman
- GI Division, UCL Hospitals NHS Foundation Trust, London, UK
- Liver Unit, Royal Free London NHS Foundation Trust, London, UK
| | | | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, University Health Network and University of Toronto, Toronto, Canada
| | | | - Simon M Rushbrook
- Department of Hepatology, Norfolk and Norwich University Hospitals NHS Trust, Norwich, UK
| | | | | | - Jessica K Dyson
- Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - David Ej Jones
- Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - Imran Patanwala
- Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
- University of Liverpool, Liverpool, UK
| | | | | | - Stephen P Pereira
- GI Division, UCL Hospitals NHS Foundation Trust, London, UK
- Institute for Liver & Digestive Health, University College London, London, UK
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32
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Dalekos GN, Gatselis NK. Variant and Specific Forms of Autoimmune Cholestatic Liver Diseases. Arch Immunol Ther Exp (Warsz) 2019; 67:197-211. [PMID: 31165900 DOI: 10.1007/s00005-019-00550-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Accepted: 05/31/2019] [Indexed: 12/12/2022]
Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the main autoimmune cholestatic liver diseases. IgG4-associated sclerosing cholangitis is another distinct immune-mediated cholestatic disorder of unknown aetiology that is frequently associated with autoimmune pancreatitis or other IgG4-related diseases. Although the majority of PBC and PSC patients have a typical presentation, there are common and uncommon important variants or specific subgroups that observed in everyday routine clinical practice. In this updated review, we summarize the published data giving also our own experience on the variants and specific groups of autoimmune cholestatic liver diseases. Actually, we give in detail the underlining difficulties and the rising dilemmas concerning the diagnosis and management of these special conditions in the clinical spectrum of autoimmune cholestatic liver diseases including the IgG4-associated sclerosing cholangitis highlighting also the uncertainties and the potential new eras of the research agenda.
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Affiliation(s)
- George N Dalekos
- Institute of Internal Medicine and Hepatology, Larissa, Greece.
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 41110, Larissa, Greece.
| | - Nikolaos K Gatselis
- Institute of Internal Medicine and Hepatology, Larissa, Greece
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 41110, Larissa, Greece
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van den Brand FF, van der Veen KS, de Boer YS, van Gerven NM, Lissenberg-Witte BI, Beuers U, van Erpecum KJ, van Buuren HR, den Ouden JW, Brouwer JT, Vrolijk JM, Verdonk RC, van Hoek B, Koek GH, Drenth JPH, Guichelaar MMJ, Mulder CJJ, Bloemena E, van Nieuwkerk CMJ, Bouma G. Increased Mortality Among Patients With vs Without Cirrhosis and Autoimmune Hepatitis. Clin Gastroenterol Hepatol 2019; 17:940-947.e2. [PMID: 30291909 DOI: 10.1016/j.cgh.2018.09.046] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 09/18/2018] [Accepted: 09/19/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS There have been few reproducible studies of mortality in patients with autoimmune hepatitis (AIH) and its variants. We calculated mortality in a large national cohort of patients with AIH, with vs without cirrhosis, in the Netherlands. METHODS We collected data from 449 patients with established AIH (77% female), from 6 academic and 10 non-academic hospitals in the Netherlands. We identified 29 patients with AIH and primary biliary cholangitis and 35 patients with AIH and primary sclerosing cholangitis (AIH-PSC). Mortality and liver transplantation data were assessed from August 1, 2006 through July 31, 2016. Standardized mortality ratios (SMR) were calculated using age-, sex-, and calendar year-matched mortality for the general Dutch population. RESULTS During the 10-year follow-up period, 60 patients (13%) died (mean age, 71 years; range, 33-94 years). Twenty-six causes of death were liver related (43%), whereas the others could not be attributed to liver disease. Patients with AIH and cirrhosis had significantly higher mortality than the general population (SMR, 1.9; 95% CI, 1.2-3.4), whereas patients without cirrhosis did not (SMR, 1.2; 95% CI, 0.8-1.8). Patients with AIH-PSC had the largest increase in mortality, compared to the general population (SMR, 4.7; 95% CI, 1.5-14.6), of all groups analyzed. Mortality in patients with AIH and primary biliary cholangitis was not greater than the general population. Four or more relapses per decade or not achieving remission was associated with an increase in liver-related death or liver transplantation. Nine patients underwent liver transplantation; 2 died from non-liver related causes. Four of 9 patients on the waitlist for transplantation died before receiving a donated liver. CONCLUSION In an analysis of data from a large national cohort of patients with AIH, we found increased mortality of patients with cirrhosis, but not of patients without cirrhosis, compared to the general Dutch population. Survival was significantly reduced in patients with AIH and features of concurrent PSC.
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Affiliation(s)
- Floris F van den Brand
- Amsterdam Gastroenterology and Metabolism, Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Koen S van der Veen
- Amsterdam Gastroenterology and Metabolism, Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Ynto S de Boer
- Amsterdam Gastroenterology and Metabolism, Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Nicole M van Gerven
- Amsterdam Gastroenterology and Metabolism, Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Birgit I Lissenberg-Witte
- Department of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Karel J van Erpecum
- Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, the Netherlands
| | - Henk R van Buuren
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Jannie W den Ouden
- Department of Gastroenterology and Hepatology, Haga Hospital, The Hague, the Netherlands
| | - Johannus T Brouwer
- Department of Gastroenterology and Hepatology, Reinier de Graaf Groep, Delft, the Netherlands
| | - Jan M Vrolijk
- Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands
| | - Robert C Verdonk
- Department of Gastroenterology and Hepatology, Sint Antonius Hospital, Nieuwegein, the Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Ger H Koek
- Department of Internal Medicine, division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Joost P H Drenth
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Marleen M J Guichelaar
- Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, the Netherlands
| | - Chris J J Mulder
- Amsterdam Gastroenterology and Metabolism, Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Elisabeth Bloemena
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Carin M J van Nieuwkerk
- Amsterdam Gastroenterology and Metabolism, Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Gerd Bouma
- Amsterdam Gastroenterology and Metabolism, Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
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Primary Sclerosing Cholangitis: A Concise Review of Diagnosis and Management. Dig Dis Sci 2019; 64:632-642. [PMID: 30725292 DOI: 10.1007/s10620-019-05484-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 01/19/2019] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterized by progressive idiopathic stricturing of the biliary system, typically leading to cirrhosis, end-stage liver disease, and colonic or hepatobiliary malignancy. Its presentation is often that of asymptomatic alkaline phosphatase elevation. When symptoms are present, they typically include fatigue, pruritus, or jaundice. The diagnosis can be confirmed via cholangiography, either magnetic resonance cholangiography (MRCP) or endoscopic retrograde cholangiography if the former is inconclusive. The clinical course is marked by progressive liver disease leading to cirrhosis with its attendant complications of portal hypertension, often including recurrent episodes of cholangitis. Greater elevation in alkaline phosphatase or liver stiffness is associated with worse clinical outcomes. Management includes endoscopic treatment of symptomatic biliary strictures and evaluation of dominant strictures as no adequate medical treatment is available. Multiple medical therapies are under evaluation. Ultimately, liver transplantation may be necessary for management of decompensated cirrhosis or disabling symptoms. There is also a markedly increased risk of cancer, notably including cholangiocarcinoma and gallbladder and colorectal cancers (particularly in patients with colitis). Cancer screening can be done with semi-annual liver imaging (MRCP or ultrasound) and colonoscopy every 1-2 years in those with colitis.
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Floreani A, De Martin S, Secchi MF, Cazzagon N. Extrahepatic autoimmunity in autoimmune liver disease. Eur J Intern Med 2019; 59:1-7. [PMID: 30360943 DOI: 10.1016/j.ejim.2018.10.014] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 10/16/2018] [Indexed: 02/07/2023]
Abstract
The most important autoimmune liver disease include: autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. In general, about one in three patients with an autoimmune liver disease have a concomitant extrahepatic autoimmune disease, which may include rheumatological, endocrinological, gastrointestinal, pulmonary or dermatological conditions. The pathogenesis of these conditions includes the production of both innate and adaptive immune responses targeting cholangiocytes as well as different extrahepatic tissues. In this sense, extrahepatic autoimmunity represent a continuous spectrum of autoimmunity involving liver and extrahepatic tissues. This review aims to focus the clinical and pathophysiological aspects of extrahepatic autoimmunity associated to autoimmune liver diseases.
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Affiliation(s)
- Annarosa Floreani
- Dept of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, 35128, Italy.
| | - Sara De Martin
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Maria Francesca Secchi
- Dept of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, 35128, Italy
| | - Nora Cazzagon
- Dept of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, 35128, Italy
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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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Isayama H, Tazuma S, Kokudo N, Tanaka A, Tsuyuguchi T, Nakazawa T, Notohara K, Mizuno S, Akamatsu N, Serikawa M, Naitoh I, Hirooka Y, Wakai T, Itoi T, Ebata T, Okaniwa S, Kamisawa T, Kawashima H, Kanno A, Kubota K, Tabata M, Unno M, Takikawa H. Clinical guidelines for primary sclerosing cholangitis 2017. J Gastroenterol 2018; 53:1006-1034. [PMID: 29951926 PMCID: PMC8930933 DOI: 10.1007/s00535-018-1484-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 06/11/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is relatively rare disease and pathogenesis and methods of treatments were still not established. Then, we had conducted the making clinical guidelines to manage patients with PSC based on the literature review and expert opinions. These clinical guidelines were made for the medical doctors on the management of PSC, except child case of PSC. METHODS We had employed modified Delphi method. The production committee decided guidelines, strength of recommendations and evidence level after reviewed literatures systematically, and The Expert panel evaluated those. The Scientific Committee of the Japan Biliary Association (JBA) evaluated revised guidelines, and the Public comments were collected on web site of JBA. RESULTS We had made 16 guidelines about epidemiology/pathophysiology, diagnostics, therapy and prognosis. Also, we had made both diagnostic and therapeutic flow chart. CONCLUSIONS We hope that these guidelines will contribute to the improvement and development of the medical care of PSC.
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Affiliation(s)
- Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Susumu Tazuma
- Department of General Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Toshio Tsuyuguchi
- Department of Medicine and Gastroenterology, Chiba University, Chiba, Japan
| | - Takahiro Nakazawa
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Suguru Mizuno
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Yoshiki Hirooka
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Takao Itoi
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shinji Okaniwa
- Department of Gastroenterology, Iida Municipal Hospital, Nagano, Japan
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Komagome Metropolitan Hospital, Tokyo, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Atsushi Kanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Keiichi Kubota
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Masami Tabata
- Department of Surgery, Matsusaka Central General Hospital, Matsusaka, Mie, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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Dyson JK, Beuers U, Jones DEJ, Lohse AW, Hudson M. Primary sclerosing cholangitis. Lancet 2018; 391:2547-2559. [PMID: 29452711 DOI: 10.1016/s0140-6736(18)30300-3] [Citation(s) in RCA: 282] [Impact Index Per Article: 40.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Revised: 11/24/2017] [Accepted: 01/03/2018] [Indexed: 12/13/2022]
Abstract
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterised by intrahepatic or extrahepatic stricturing, or both, with bile duct fibrosis. Inflammation and fibrosis of bile ducts and the liver are followed by impaired bile formation or flow and progressive liver dysfunction. Patients might be asymptomatic at presentation or might have pruritus, fatigue, right upper quadrant pain, recurrent cholangitis, or sequelae of portal hypertension. The key diagnostic elements are cholestatic liver biochemistry and bile duct stricturing on cholangiography. Genetic and environmental factors are important in the cause of the disease, with the intestinal microbiome increasingly thought to play a pathogenetic role. Approximately 70% of patients have concurrent inflammatory bowel disease and patients require colonoscopic screening and surveillance. Primary sclerosing cholangitis is associated with increased malignancy risk and surveillance strategies for early cholangiocarcinoma detection are limited. No single drug has been proven to improve transplant-free survival. Liver transplantation is effective for advanced disease but at least 25% of patients develop recurrent disease in the graft.
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Affiliation(s)
- Jessica K Dyson
- Department of Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - David E J Jones
- Department of Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - Ansgar W Lohse
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Mark Hudson
- Department of Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, Newcastle, UK
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Hirschfield GM, Beuers U, Corpechot C, Invernizzi P, Jones D, Marzioni M, Schramm C. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017; 67:145-172. [PMID: 28427765 DOI: 10.1016/j.jhep.2017.03.022] [Citation(s) in RCA: 884] [Impact Index Per Article: 110.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 03/23/2017] [Indexed: 02/07/2023]
Abstract
Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune cholestatic liver disease, which when untreated will culminate in end-stage biliary cirrhosis. Diagnosis is usually based on the presence of serum liver tests indicative of a cholestatic hepatitis in association with circulating antimitochondrial antibodies. Patient presentation and course can be diverse and risk stratification is important to ensure all patients receive a personalised approach to their care. The goals of treatment and management are the prevention of end-stage liver disease, and the amelioration of associated symptoms. Pharmacologic approaches in practice, to reduce the impact of the progressive nature of disease, currently include licensed therapies (ursodeoxycholic acid and obeticholic acid) and off-label therapies (fibric acid derivatives, budesonide). These clinical practice guidelines summarise the evidence for the importance of a structured, life-long and individualised, approach to the care of patients with PBC, providing a framework to help clinicians diagnose and effectively manage patients.
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Czaja AJ, Carpenter HA. Autoimmune Hepatitis Overlap Syndromes and Liver Pathology. Gastroenterol Clin North Am 2017; 46:345-364. [PMID: 28506369 DOI: 10.1016/j.gtc.2017.01.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
Autoimmune hepatitis (AIH) may have an atypical serum alkaline phosphatase elevation, antimitochondrial antibodies, histologic features of bile duct injury/loss, or cholangiographic findings of focal biliary strictures and dilations. These manifestations characterize the overlap syndromes. Patients can be classified as having AIH with features of primary biliary cholangitis, primary sclerosing cholangitis, or a cholestatic syndrome. The gold standard of diagnosis is clinical judgment. Histologic evaluation is a major diagnostic component. Treatment is based on algorithms; outcomes vary depending on the predominant disease component. Combination therapy has been the principal recommendation.
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Affiliation(s)
- Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA.
| | - Herschel A Carpenter
- Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA
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Wong GW, Yeong T, Lawrence D, Yeoman AD, Verma S, Heneghan MA. Concurrent extrahepatic autoimmunity in autoimmune hepatitis: implications for diagnosis, clinical course and long-term outcomes. Liver Int 2017; 37:449-457. [PMID: 27541063 DOI: 10.1111/liv.13236] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 08/13/2016] [Indexed: 02/13/2023]
Abstract
BACKGROUND Concurrent extrahepatic autoimmune disease (CEHAID) associated with autoimmune hepatitis (AIH) have been incorporated into the diagnostic criteria stipulated by the International Autoimmune Hepatitis Group (IAIHG). Large comprehensive cohort data on the extrahepatic autoimmunity in AIH remain scanty. AIM To systematically assess features and clinical impact of CEHAID on AIH. METHODS Clinical records of 562 patients with AIH from two tertiary centres in the UK were retrospectively reviewed. RESULTS Prevalence of CEHAID in patients with AIH was 42%. Autoimmune thyroid disease was the commonest CEHAID associated with AIH (101/562, 18%). Autoimmune skin diseases were more prevalent in AIH-2 than AIH-1 (21.9% vs 7%, P=.009). Personal history of CEHAID was more commonly found in AIH patients with than without first-degree family history of CEHAID [48/86 (55.8%) vs 169/446 (37.9%), P=.002]. AIH patients with CEHAID were more often women (85.2% vs 76.1%, P=.008), had higher post-treatment IAIHG score (22 vs 20, P<.001), less reactivity to smooth muscle antibodies (49.8% vs 65%, P<.001), more likely to have mild fibrosis at diagnosis (20.9% vs 6.5%, P<.001) and less often had ascites (6.3% vs 13.6%, P=.008) and coagulopathy (1.18 vs 1.27, P=.013) at presentation. Presence of CEHAID, however, did not significantly affect disease progression, prognosis and survival in AIH. CONCLUSIONS Our study confirms the strong association of CEHAID with AIH. Association between personal and familial extrahepatic autoimmunity especially among first-degree relatives was evident. Presence of CEHAID may influence clinical phenotype of AIH at presentation, but without notable impact on the long-term clinical outcomes.
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Affiliation(s)
- Guan-Wee Wong
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Tian Yeong
- Department of Medicine, Brighton and Sussex Medical School, Brighton, UK
| | - David Lawrence
- Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospital, Brighton, UK
| | - Andrew D Yeoman
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Sumita Verma
- Department of Medicine, Brighton and Sussex Medical School, Brighton, UK.,Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospital, Brighton, UK
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Serum Cytokine Levels and Their Relation to Clinical Features in Patients with Autoimmune Liver Diseases. J Immunol Res 2017; 2017:9829436. [PMID: 28299346 PMCID: PMC5337382 DOI: 10.1155/2017/9829436] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 02/01/2017] [Indexed: 01/30/2023] Open
Abstract
Serum cytokine levels were explored in a combined group of patients with autoimmune liver diseases (AILDs) and separately in patients with autoimmune hepatitis (AIH) and overlap syndrome. Overall, 60 patients with AILD, among them 32 patients with AIH and 28 patients with overlap syndrome, were included in the cross-sectional study. Serum cytokine levels were measured at baseline and compared to those of 21 healthy controls. Patients with AILD had significantly higher levels of IL-6 (0.70 (range 0.17–99.86) in patients with AILD compared to 0.40 (range 0.14–2.65) in controls, p < 0.01), IL-8 (1.66 (0.45–34.58) versus 0.53 (0.35–2.38), resp., p < 0.01), and TNF-α (2.61 (0.23–120.88) versus 1.65 (0.21–7.54), resp., p < 0.01). Adjusted logistic regression analysis revealed a pronounced relation of IL-8 and AILD, 48.36 (3.63–643.60), as well as AIH, 18.54 (1.08–318.54), and overlap syndrome, 23.85 (2.37–240.23), while the associations between the level of other cytokines and AILD were assessed as nonsignificant. In the language of absolute numbers, the increase of IL-8 serum level by 1 pg/mL had increased the chance for a patient to find himself in a group of AILD by 48.36 times. Also, high IL-8 serum levels were strongly related to clinical parameters.
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Igarashi G, Endo T, Mikami K, Sawada N, Satake R, Ohta R, Sakamoto J, Yoshimura T, Kurose A, Kijima H, Fukuda S. Two Cases of Primary Sclerosing Cholangitis Overlapping with Autoimmune Hepatitis in Adults. Intern Med 2017; 56:509-515. [PMID: 28250296 PMCID: PMC5399201 DOI: 10.2169/internalmedicine.56.7633] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Overlap syndrome between primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) is extremely rare in Japan. We herein report two adult patients with PSC-AIH overlap syndrome. They were diagnosed with PSC-AIH overlap syndrome based on the findings of endoscopic retrograde cholangiography and liver biopsy, and using the International Autoimmune Hepatitis Group scoring system. In both cases, PSC preceded AIH, and combination therapy with steroid and ursodeoxycholic acid was effective. Because there are few reported cases in Japan, it is important to study more cases to shed light on the clinical and pathological features of PSC-AIH overlap syndrome.
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Affiliation(s)
- Go Igarashi
- Department of Gastroenterology and Hematology, Hirosaki Graduate School of Medicine, Japan
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Hübener S, Oo YH, Than NN, Hübener P, Weiler-Normann C, Lohse AW, Schramm C. Efficacy of 6-Mercaptopurine as Second-Line Treatment for Patients With Autoimmune Hepatitis and Azathioprine Intolerance. Clin Gastroenterol Hepatol 2016; 14:445-53. [PMID: 26492846 DOI: 10.1016/j.cgh.2015.09.037] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Revised: 09/01/2015] [Accepted: 09/30/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that requires long-term immunosuppressive therapy. Although most patients have an excellent response to standard therapy (azathioprine in combination with corticosteroids), approximately 10%-15% have intolerance or an insufficient response to azathioprine treatment. We investigated whether 6-mercaptopurine (6-MP) is an effective second-line therapy for patients with AIH. METHODS We performed a retrospective study of 22 patients with AIH who were switched to 6-MP therapy after treatment with the combination of azathioprine and prednisolone at 2 tertiary care institutions in Europe (Germany and the United Kingdom) before November 15, 2014. We performed statistical analyses of data on clinical and biochemical responses collected 4 weeks after 6-MP treatment and then at regular physician visits. RESULTS A total of 15 of 20 patients with prior azathioprine intolerance (75%) responded to 6-MP treatment; 8 of these patients had a complete response and 7 had partial remission, based on biochemical features. In these 15 patients, 6-MP was well tolerated, whereas the 5 remaining patients had to be switched to different immunosuppressive regimes because of 6-MP intolerance. The 2 patients with insufficient response to azathioprine treatment also showed no response to 6-MP. CONCLUSIONS In patients with AIH and azathioprine intolerance, 6-MP seems to be an effective and well-tolerated second-line treatment. 6-MP might be ineffective in patients with insufficient response to azathioprine.
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Affiliation(s)
- Sina Hübener
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ye Htun Oo
- Centre for Liver Research, University of Birmingham Liver Unit, Birmingham, United Kingdom
| | - Nwe Ni Than
- Centre for Liver Research, University of Birmingham Liver Unit, Birmingham, United Kingdom
| | - Peter Hübener
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Ansgar W Lohse
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Schramm
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Bittencourt PL, Cançado ELR, Couto CA, Levy C, Porta G, Silva AEB, Terrabuio DRB, Carvalho Filho RJD, Chaves DM, Miura IK, Codes L, Faria LC, Evangelista AS, Farias AQ, Gonçalves LL, Harriz M, Lopes Neto EPA, Luz GO, Oliveira P, Oliveira EMGD, Schiavon JLN, Seva-Pereira T, Parise ER, Parise ER. Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver. ARQUIVOS DE GASTROENTEROLOGIA 2015; 52 Suppl 1:15-46. [DOI: 10.1590/s0004-28032015000500002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
ABSTRACT In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.
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Affiliation(s)
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- EASL office, 7 Rue Daubin, CH 1203 Geneva, Switzerland,
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Aguilar-Nájera O, Velasco-Zamora JA, Torre A. Overlap syndromes of autoimmune hepatitis: diagnosis and treatment. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2015; 80:150-9. [PMID: 26091564 DOI: 10.1016/j.rgmx.2015.04.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 04/21/2015] [Accepted: 04/23/2015] [Indexed: 12/17/2022]
Abstract
Some patients with autoimmune liver disease have characteristics of cholestasis, as well as of autoimmune hepatitis. Despite the fact that this is a relatively frequent clinical condition seen in referral centers for liver diseases, there is little evidence as regards the clinical management of these syndromes due to their low prevalence and the lack of standardized definitions and diagnostic criteria. This is relevant, given that published studies report that there is a lower therapeutic response and poorer outcome in patients with overlap syndrome than in those presenting solely with autoimmune hepatitis. Whether overlap syndromes are distinct entities or the presence of 2 concurrent diseases is still a subject of debate. They should be suspected in autoimmune hepatitis patients that present with signs of cholestasis, as it is known that overlap behavior tends to be more aggressive, with higher rates of cirrhosis and the need for liver transplantation. Treatment response is also poorer and should be directed at the predominant component. Standardized definitions are necessary so that these syndromes can be studied in controlled clinical trials.
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Affiliation(s)
- O Aguilar-Nájera
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D.F., México
| | - J A Velasco-Zamora
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D.F., México
| | - A Torre
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D.F., México.
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Liaskou E, Hirschfield GM. Genetic Distinctions in Patients With Primary Sclerosing Cholangitis: Immunoglobulin G4 Elevations and HLA Risk. Gastroenterology 2015; 148:886-9. [PMID: 25805418 DOI: 10.1053/j.gastro.2015.03.021] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Affiliation(s)
- Evaggelia Liaskou
- Centre for Liver Research, NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, Birmingham, UK
| | - Gideon M Hirschfield
- Centre for Liver Research, NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, Birmingham, UK.
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Overlap syndromes of autoimmune hepatitis: diagnosis and treatment. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2015. [DOI: 10.1016/j.rgmxen.2015.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
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Kang YZ, Sun XY, Liu YH, Shen ZY. Autoimmune hepatitis-primary biliary cirrhosis concurrent with biliary stricture after liver transplantation. World J Gastroenterol 2015; 21:2236-41. [PMID: 25717264 PMCID: PMC4326166 DOI: 10.3748/wjg.v21.i7.2236] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 08/28/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023] Open
Abstract
Although the development of de novo autoimmune liver disease after liver transplantation (LT) has been described in both children and adults, autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome has rarely been seen in liver transplant recipients. Here, we report a 50-year-old man who underwent LT for decompensated liver disease secondary to alcoholic steatohepatitis. His liver function tests became markedly abnormal 8 years after LT. Standard autoimmune serological tests were positive for anti-nuclear and anti-mitochondrial antibodies, and a marked biochemical response was observed to a regimen consisting of prednisone and ursodeoxycholic acid added to maintain immunosuppressant tacrolimus. Liver biopsy showed moderate bile duct lesions and periportal lymphocytes infiltrating along with light fibrosis, which confirmed the diagnosis of AIH-PBC overlap syndrome. We believe that this may be a case of post-LT de novo AIH-PBC overlap syndrome; a novel type of autoimmune overlap syndrome.
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