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Gandhi HJ, Jain S, Chandnani S, Malokar RN, Chudasama J, Patel S, Pandey D, Mavuri V, Kamat R, Rathi P. Predictors of Mortality in Patients Diagnosed With Autoimmune Hepatitis - Insights from a Prospective, 90-day Follow--up Study. J Clin Exp Hepatol 2025; 15:102546. [PMID: 40242057 PMCID: PMC11999594 DOI: 10.1016/j.jceh.2025.102546] [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: 10/01/2024] [Accepted: 03/07/2025] [Indexed: 04/18/2025] Open
Abstract
Background and aims The response to corticosteroids and optimal timing for liver transplantation (LT) in patients with autoimmune hepatitis (AIH) remain significant clinical challenges. This study aimed to assess short-term (90-day) mortality in patients with acute AIH (with or without underlying cirrhosis and chronic liver disease) treated with corticosteroids, and to identify factors that predict mortality in this population. Methods We conducted a prospective, single-center study between 2022 and 2024, involving patients with histologically confirmed AIH. All patients received corticosteroid treatment and were monitored for various clinical and laboratory parameters on days 3, 7, and 90 after initiating therapy. Results A total of 104 patients were included in the study, with a mean age of 46.1 ± 14.3 years; 77% of the patients were female. The 90-day mortality rate following the initiation of corticosteroids was 13.47%. Univariate analysis identified several significant predictors of mortality, including older age, diabetes mellitus, cirrhosis, esophageal varices, hepatic encephalopathy, low serum albumin on day 3, model of end-stage liver disease (MELD) scores on days 3 and 7, and the survival and prognostic factors for acute severe autoimmune hepatitis (SURFASA) score (P < 0.05). Multivariate analysis revealed that MELD score on day 7 (odds ratio [OR] 1.25; 95% confidence interval [CI] {1.09-1.48}; P = 0.00) and SURFASA score (OR 7.46; 95% CI {1.05-53.06}; P = 0.04) were significant. Specifically, a MELD score ≥27.5 on day 7 (area under the receiver operating characteristic curve [AUC] = 0.998) with 100% sensitivity and 97.8% specificity, and a SURFASA score ≥ -2.95 (AUC = 0.969) with 100% sensitivity and 95.6% specificity were highly predictive of mortality. Conclusion Despite corticosteroid treatment, mortality rates remain high in the decompensated AIH and acute on chronic liver failure-AIH groups. The SURFASA score, along with MELD scores on days 3 and 7, are strong predictors of mortality and can assist clinicians in making timely decisions regarding referral for early liver transplantation.
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Affiliation(s)
- Harsh J. Gandhi
- Department of Gastroenterology, TNMC BYL Nair Ch Hospital, Mumbai, India
| | - Shubham Jain
- Department of Gastroenterology, TNMC BYL Nair Ch Hospital, Mumbai, India
| | - Sanjay Chandnani
- Department of Gastroenterology, TNMC BYL Nair Ch Hospital, Mumbai, India
| | | | - Jay Chudasama
- Department of Gastroenterology, TNMC BYL Nair Ch Hospital, Mumbai, India
| | - Sameet Patel
- Department of Gastroenterology, TNMC BYL Nair Ch Hospital, Mumbai, India
| | - Deepika Pandey
- Department of Gastroenterology, TNMC BYL Nair Ch Hospital, Mumbai, India
| | - Vishal Mavuri
- Department of Gastroenterology, TNMC BYL Nair Ch Hospital, Mumbai, India
| | - Rima Kamat
- Department of Pathology, TNMC BYL Nair Ch Hospital, Mumbai, India
| | - Pravin Rathi
- Department of Gastroenterology, TNMC BYL Nair Ch Hospital, Mumbai, India
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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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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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Sanei MH, Tamizifar B, Mardani E, Ghaderi A, Tarigholeslami E, Sanei M. Comparative Evaluation of Simplified and Modified Histologic Criteria in the Diagnosis of Chronic Autoimmune Hepatitis. Adv Biomed Res 2025; 14:21. [PMID: 40303626 PMCID: PMC12039868 DOI: 10.4103/abr.abr_294_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 11/19/2023] [Accepted: 11/27/2023] [Indexed: 05/02/2025] Open
Abstract
Background The present study aimed at comparing simplified and modified histologic criteria alone and along with other indicators in the diagnosis of chronic autoimmune hepatitis (AIH). Materials and Methods In this cross-sectional study, 48 cases were selected from slides and paraffin blocks of patients suspected of chronic AIH according to clinical and laboratory data, including serology and autoantibody findings and viral hepatitis test results. Then, scores equal to 1 (compatible hepatitis), 2 (typical hepatitis), ≤6 (probable hepatitis), and ≥7 (definite hepatitis) were calculated based on the simplified histologic criteria, modified histologic criteria, and these two criteria, along with other indicators including antinuclear antibodies (Ab), smooth muscle Ab or liver-kidney microsomal Ab or soluble liver antigen (Ag) and serum immunoglobulin G (IgG) and absence of viral hepatitis. Results The results of this study revealed that based on the simplified histologic criteria, 43.8% and 56.3% of these cases were assigned a score of 1 and 2 points, respectively. However, calculating the total score using the simplified criteria along with other indicators showed that 60.4% and 39.6% of cases were assigned a score ≤6 and ≥7 points, respectively. Moreover, the modified histologic criteria indicated that 25% and 75% of cases were assigned a score of 1 and 2 points, respectively. Conclusion According to the findings of the present study, the modified histologic criteria compared to the simplified histologic criteria identified a higher percentage of patients assigned a score of 2 points. Moreover, modified histologic criteria, along with other indicators, were more accurate in detecting definite AIH (score ≥7 points).
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Affiliation(s)
- Mohammad H. Sanei
- Department of Pathology, Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Babak Tamizifar
- Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Elahe Mardani
- Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amir Ghaderi
- Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Maryam Sanei
- Department of General Physician, Isfahan University of Medical Sciences, Isfahan, Iran
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Wang Y, Su Y, Guo T, Zhao M, Liu L, Chen W, Zhao X. Immune-mediated liver injury caused by immune checkpoint inhibitors exhibits distinct clinical features that differ from autoimmune hepatitis. Expert Opin Drug Metab Toxicol 2024:1-9. [PMID: 39665399 DOI: 10.1080/17425255.2024.2434642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 11/20/2024] [Indexed: 12/13/2024]
Abstract
BACKGROUND Immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI) and autoimmune hepatitis (AIH) are both related to the distorted immune system. However, ILICI differs from AIH in several distinct ways. We aimed to study the differences between ILICI and AIH. RESEARCH DESIGN AND METHODS This is a retrospective study collecting clinical data of ILICI (2016.1-2024.2) and AIH (2002.1-2023.6) patients. Demographic, clinicopathological, radiological characteristics, treatment and outcomes were analyzed. RESULTS A total of 71 ILICI and 158 AIH cases were included. ILICI group had older patients and fewer females (age: 66 vs. 56 years, gender: 28.2% vs. 85.4%, p < 0.001). They had lower ALT, AST, TBil, IgG levels, and lower titers of ANA. Some ILICI patients exhibited bile duct edema and dilation, while AIH patients typically had liver fibrosis in CT/MRI. Histologically, ILICI showed bile duct injury, inflammatory cells infiltration with fewer plasma cells. Glucocorticoid treatment was less common, but ALT level recovery was faster in ILICI patients (41 vs. 140 days, p < 0.001). CONCLUSIONS ILICI generally affects older patients without a female predilection and is linked to milder, acute liver injury. High ANA titers, elevated IgG, and prominent plasma cell infiltration were less common. Liver function normalizes more quickly in ILICI.
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Affiliation(s)
- Yan Wang
- Liver Research Center, Beijing Friendship Hospital, Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Disease, Capital Medical University, Beijing, China
| | - Yu Su
- Liver Research Center, Beijing Friendship Hospital, Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Disease, Capital Medical University, Beijing, China
| | - Tiantian Guo
- Liver Research Center, Beijing Friendship Hospital, Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Disease, Capital Medical University, Beijing, China
| | - Mengyu Zhao
- Liver Research Center, Beijing Friendship Hospital, Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Disease, Capital Medical University, Beijing, China
| | - Liwei Liu
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Wei Chen
- Department of Gastroenterology, Beijing Friendship Hospital, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Capital Medical University, Beijing, China
| | - Xinyan Zhao
- Liver Research Center, Beijing Friendship Hospital, Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Disease, Capital Medical University, Beijing, China
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Wang L, Du ZX, Liu HL, Zhang Y, Wang SS, Hu YF, Li LQ, Zhu P, Zhong YD, Xiong QF, Yang YF. IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China. Liver Int 2024; 44:2282-2292. [PMID: 38775078 DOI: 10.1111/liv.15971] [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: 09/20/2023] [Revised: 04/28/2024] [Accepted: 04/30/2024] [Indexed: 08/30/2024]
Abstract
BACKGROUND AND AIMS The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.
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Affiliation(s)
- Li Wang
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhi-Xiang Du
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | | | - Yu Zhang
- Southeast University, Nanjing, China
| | | | - Yi-Fan Hu
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Li-Qiu Li
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Ping Zhu
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Yan-Dan Zhong
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Qing-Fang Xiong
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Yong-Feng Yang
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
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Pedersen MR, Mayo MJ. Advances in the evaluation and treatment of autoimmune hepatitis. Curr Opin Gastroenterol 2024; 40:126-133. [PMID: 38363233 DOI: 10.1097/mog.0000000000001014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/17/2024]
Abstract
PURPOSE OF REVIEW The primary therapy of autoimmune hepatitis (AIH) has been established for over three decades. This review focuses on updates in the evaluation and management of patients with AIH. RECENT FINDINGS The evaluation of patients has recently been updated to include more definitive screening for other autoimmune diseases, including thyroid disease and celiac disease. Antibody detection by ELISA, an easier and more commonly available method, has been incorporated into the latest iteration of the AIH scoring system. Corticosteroids and AZA remain the backbone of AIH treatment, but there is growing evidence for mycophenolate mofetil as both first-line and second-line therapy, and growing inquiry into calcineurin inhibitors. Noninvasive markers of liver disease have now been validated in AIH, with the strongest evidence for VCTE in patients with minimal hepatic inflammation. SUMMARY Recent research of alternative immunosuppressant therapies, noninvasive markers of fibrosis, and updated society guidelines, have improved our ability to evaluate, treat, and follow patients with AIH.
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Affiliation(s)
- M R Pedersen
- Division of Digestive and Liver Disease, University of Texas Southwestern Medical Center, Harry Hines Blvd, Dallas, Texas, USA
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Mercado LA, Gil-Lopez F, Chirila RM, Harnois DM. Autoimmune Hepatitis: A Diagnostic and Therapeutic Overview. Diagnostics (Basel) 2024; 14:382. [PMID: 38396421 PMCID: PMC10887775 DOI: 10.3390/diagnostics14040382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 02/02/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Autoimmune hepatitis is an immune-mediated inflammatory condition of the liver of undetermined cause that affects both sexes, all ages, races, and ethnicities. Its clinical presentation can be very broad, from having an asymptomatic and silent course to presenting as acute hepatitis, cirrhosis, and acute liver failure potentially requiring liver transplantation. The diagnosis is based on histological abnormalities (interface hepatitis), characteristic clinical and laboratory findings (increased aspartate aminotransferase, alanine aminotransferase, and serum IgG concentration), and the presence of one or more characteristic autoantibodies. The large heterogeneity of these clinical, biochemical, and histological findings can sometimes make a timely and proper diagnosis a difficult task. Treatment seeks to achieve remission of the disease and prevent further progression of liver disease. First-line therapy includes high-dose corticosteroids, which are later tapered to decrease side effects, and azathioprine. In the presence of azathioprine intolerance or a poor response to the standard of care, second-line therapy needs to be considered, including mycophenolate mofetil. AIH remains a diagnostic and therapeutic challenge, and a further understanding of the pathophysiological pathways of the disease and the implementation of randomized controlled trials are needed.
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Affiliation(s)
- Lydia A. Mercado
- Department of Liver Transplant, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Fernando Gil-Lopez
- Department of Liver Transplant, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Razvan M. Chirila
- Department of General Internal Medicine, Mayo Clinic Florida, Jacksonville, FL 32224, USA;
| | - Denise M. Harnois
- Department of Liver Transplant, Mayo Clinic Florida, Jacksonville, FL 32224, USA
- Department of Gastroenterology and Hepatology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
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Sakhuja P, Goyal S. Autoimmune Hepatitis: From Evolution to Current Status-A Pathologist's Perspective. Diagnostics (Basel) 2024; 14:210. [PMID: 38248086 PMCID: PMC10814110 DOI: 10.3390/diagnostics14020210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/03/2024] [Accepted: 01/15/2024] [Indexed: 01/23/2024] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic, relapsing and remitting, immune-mediated liver disease that progresses to cirrhosis if left untreated. A significant number of patients may present with acute hepatitis or acute liver failure, which are often misdiagnosed as toxic liver injury. AIH shows a preponderance in young women but may be seen in children and the elderly. Diagnosis requires the integration of clinical, biochemical, and serologic parameters, along with supportive liver histology and exclusion of other causes of liver disease. Liver biopsy is a prerequisite for diagnosis of AIH, to assess severity and stage of disease, exclude other entities, and recognize any concurrent morbidities. No single biomarker or histologic feature is pathognomonic for AIH. The diagnostic and histologic criteria have undergone several modifications since the original scoring system was proposed by the International Autoimmune Hepatitis Group (IAIHG) in 1993. Recently, the IAIHG has proposed consensus recommendations for histologic criteria, relevant for both acute and chronic AIH. This review article will describe the evolving diagnostic criteria for AIH, with their limitations and utility, and with an emphasis on the role of liver histology in the diagnosis and management of AIH.
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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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Ahn S, Jeong SH, Cho EJ, Lee K, Kim G, Kim H. Comparison of four histological scoring systems for autoimmune hepatitis to improve diagnostic sensitivity. Clin Mol Hepatol 2024; 30:37-48. [PMID: 37953068 PMCID: PMC10776291 DOI: 10.3350/cmh.2023.0325] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/20/2023] [Accepted: 11/10/2023] [Indexed: 11/14/2023] Open
Abstract
BACKGROUND/AIMS The histological criteria in the 1999 and 2008 scoring systems proposed by the International Autoimmune Hepatitis Group (IAIHG) have their inherent limitations in diagnosing autoimmune hepatitis (AIH). In this study, we evaluated the histology components of four scoring systems (1. revised original scoring system ["1999 IAIHG"], 2. simplified scoring system ["2008 IAIHG"], 3. modified histologic criteria ["2017 UCSF"], and 4. a new histologic criteria proposed by the International AIH Pathology Group ["2022 IAHPG"]) in AIH patients. METHODS Medical records and liver biopsies were retrospectively reviewed for 68 patients from two independent medical institutions, diagnosed with AIH based on the 1999 IAIHG system between 2006 and 2016. The histological features were reviewed in detail, and the four histological scoring systems were compared. RESULTS Out of the 68 patients, 56 (82.4%) patients met the "probable" or "definite" AIH criteria of the 2008 IAIHG system, and the proportion of histologic score 2 (maximum) was 40/68 (58.8%). By applying the 2017 UCSF criteria, the number of histology score 2 increased to 60/68 (88.2%), and "probable" or "definite" AIH cases increased to 61/68 (89.7%). Finally, applying the 2022 IAHPG histology score resulted in the highest number of cases with histologic score 2 (64/68; 94.1%) and with a diagnosis of "probable" or "definite" AIH (62/68; 91.2%). CONCLUSION The recently proposed UCSF/IAHPG histological criteria increased the histology score of AIH. Substituting the histology component of the 2008 IAIHG system with the 2022 IAHPG criteria increased the sensitivity for diagnosing AIH (≥"Probable AIH") from 82.4% to 91.2%.
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Affiliation(s)
- Soomin Ahn
- Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Eun Ju Cho
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kyoungbun Lee
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Gilhyang Kim
- Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
- Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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Shingina A, Mukhtar N, Wakim-Fleming J, Alqahtani S, Wong RJ, Limketkai BN, Larson AM, Grant L. Acute Liver Failure Guidelines. Am J Gastroenterol 2023; 118:1128-1153. [PMID: 37377263 DOI: 10.14309/ajg.0000000000002340] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 04/04/2023] [Indexed: 06/29/2023]
Abstract
Acute liver failure (ALF) is a rare, acute, potentially reversible condition resulting in severe liver impairment and rapid clinical deterioration in patients without preexisting liver disease. Due to the rarity of this condition, published studies are limited by the use of retrospective or prospective cohorts and lack of randomized controlled trials. Current guidelines represent the suggested approach to the identification, treatment, and management of ALF and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence was reviewed using the Grading of Recommendations, Assessment, Development and Evaluation process to develop recommendations. When no robust evidence was available, expert opinions were summarized using Key Concepts. Considering the variety of clinical presentations of ALF, individualization of care should be applied in specific clinical scenarios.
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Affiliation(s)
- Alexandra Shingina
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Nizar Mukhtar
- Department of Gastroenterology, Kaiser Permanente, San Francisco, California, USA
| | - Jamilé Wakim-Fleming
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland Ohio, USA
| | - Saleh Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
- Liver Transplantation Unit, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA
| | | | - Anne M Larson
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, Washington, USA
| | - Lafaine Grant
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
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13
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Buechter M, Dorn D, Möhlendick B, Siffert W, Baba HA, Gerken G, Kahraman A. Characteristics and Long-Term Outcome of 535 Patients with Autoimmune Hepatitis-The 20-Year Experience of a High-Volume Tertiary Center. J Clin Med 2023; 12:4192. [PMID: 37445225 DOI: 10.3390/jcm12134192] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 06/12/2023] [Accepted: 06/16/2023] [Indexed: 07/15/2023] Open
Abstract
Background and aims: Autoimmune hepatitis (AIH) is a complex and progressive inflammatory liver disease characterized by immune-mediated destruction of the liver parenchyma, hypergammaglobulinemia, the presence of circulating autoantibodies, and good response to immunosuppressive therapy. Since the prevalence of AIH is relatively rare, data on the clinical course and the long-term outcome are scarce. Patients and methods: We retrospectively analyzed the data of 535 well-documented AIH patients treated at the University Hospital Essen between 2000 and 2020. Results: The majority of patients were middle-aged females (75% women, mean age 45 years) with AIH type 1 (97%). Approximately 32% of patients were diagnosed with cirrhosis due to AIH, 29% had concomitant autoimmune (predominantly autoimmune thyroiditis), and 10% had psychiatric diseases, respectively. Skin tumors were the most common malignant diseases (47% of all tumors), while hepatocellular carcinoma rarely occurred (only six cases). Overall long-term mortality and liver-associated mortality were 9.16% and 4.67%, respectively. However, long-term survival was strongly associated with disease remission. Conclusions: Although AIH is a silent disease and cirrhosis is present in many cases, a favorable long-term prognosis can be achieved by consequent immunosuppressive therapy. The incidence of (liver-associated) complications seems to be lower in comparison to other etiologies, such as viral hepatitis or NASH, and mainly depends on the long-term side effects of immunosuppressive therapy.
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Affiliation(s)
- Matthias Buechter
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Department of Gastroenterology and Hepatology, Elisabeth Hospital, 58638 Iserlohn, Germany
| | - Dominik Dorn
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
| | - Birte Möhlendick
- Institute of Pharmacogenetics, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
| | - Winfried Siffert
- Institute of Pharmacogenetics, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
| | - Hideo A Baba
- Institute of Pathology, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
| | - Guido Gerken
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Department of Gastroenterology and Hepatology, Helios Clinic, 42549 Velbert, Germany
| | - Alisan Kahraman
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Department of Gastroenterology and Hepatology, Max Grundig Clinic, 77815 Bühl, Germany
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14
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Enke T, Livingston S, Rule J, Stravitz T, Rakela J, Bass N, Reuben A, Tujios S, Larson A, Sussman N, Durkalski V, Lee W, Ganger D. Autoimmune hepatitis presenting as acute liver failure: A 20-year retrospective review of North America. Liver Transpl 2023; 29:570-580. [PMID: 36825579 PMCID: PMC10192052 DOI: 10.1097/lvt.0000000000000105] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 01/12/2023] [Indexed: 02/25/2023]
Abstract
Autoimmune hepatitis is a common cause of acute liver failure. Treatment includes steroids for acute liver injury and liver transplantation in those who fail to respond or develop acute liver failure. The aim of this study is to further characterize acute liver failure secondary to autoimmune hepatitis and identify variables that predict 21-day transplant-free survival. This study included adults hospitalized with acute liver failure enrolled in the Acute Liver Failure Study Group Registry between 1998 and 2019 from 32 centers within the US. The etiology of all cases was reviewed by the Adjudication Committee, and all cases identified as autoimmune hepatitis were included. Acute liver injury was defined as an INR ≥2.0 without encephalopathy and acute liver failure as INR ≥ 1.5 with encephalopathy. Laboratory and clinical data were reviewed. Variables significantly associated with 21-day transplant-free survival were used to develop a multivariable logistic regression model. A total of 193 cases of acute liver failure secondary to autoimmune hepatitis were identified and reviewed. There were 161 patients (83.4%) diagnosed with acute liver failure on enrollment, and 32 (16.6%) developed acute liver failure during hospitalization. At 21 days, 115 (59.6%) underwent liver transplantation, 28 (14.5%) had transplant-free survival, and 46 (23.8%) died before liver transplantation. Higher admission values of bilirubin, INR, and coma grade were associated with worse outcomes. A prognostic index incorporating bilirubin, INR, coma grade, and platelet count had a concordance statistic of 0.84. Acute liver failure secondary to autoimmune hepatitis is associated with a high short-term mortality. We developed a model specifically for autoimmune hepatitis that may be helpful in predicting 21-day transplant-free survival and early identification of patients in need of expedited liver transplant evaluation.
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Affiliation(s)
| | | | - Jody Rule
- University of Texas Southwestern Medical Center
| | | | | | - Nathan Bass
- University of California San Francisco Medical Center
| | | | | | | | | | | | - William Lee
- University of Texas Southwestern Medical Center
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15
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Gerussi A, Halliday N, Carbone M, Invernizzi P, Thorburn D. Open challenges in the management of autoimmune hepatitis. Minerva Gastroenterol (Torino) 2023; 69:61-83. [PMID: 33267568 DOI: 10.23736/s2724-5895.20.02805-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/02/2023]
Abstract
Autoimmune hepatitis (AIH) is a rare autoimmune disease of the liver with many open questions as regards its etiopathogenesis, natural history and clinical management. The classical picture of AIH is chronic hepatitis with fluctuating elevation of serum transaminases and Immunoglobulin G levels, the presence of circulating autoantibodies and typical histological features. However, atypical presentations do occur and are not well captured by current diagnostic scores, with important consequences in terms of missed diagnoses and delayed treatments. AIH is treated with corticosteroids and immunosuppressive drugs but up to 40% of patients do not achieve full biochemical response and are at risk of progressing to cirrhosis and liver failure. Moreover, standard therapies are associated by significant side-effects which may impair the quality of life of patients living with AIH. However, advances in the understanding of the underlying immunology of AIH is raising the prospect of novel therapies and optimization of existing therapeutic approaches to reduce side-effect burdens and potentially restore immunological tolerance. In this review we outlined the clinical characteristics, etiopathogenesis and management of AIH and current challenges in the diagnosis and management of AIH and provided evidence underlying the evolution of diagnostic and clinical management protocols.
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Affiliation(s)
- Alessio Gerussi
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milano-Bicocca, Monza, Monza-Brianza, Italy - .,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Monza-Brianza, Italy - .,Ancient DNA Lab Dan David Center for Human Evolution and Biohistory Research, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel -
| | - Neil Halliday
- Institute for Liver and Digestive Health, University College London, London, UK
| | - Marco Carbone
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milano-Bicocca, Monza, Monza-Brianza, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Monza-Brianza, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milano-Bicocca, Monza, Monza-Brianza, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Monza-Brianza, Italy
| | - Douglas Thorburn
- Institute for Liver and Digestive Health, University College London, London, UK
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16
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Abstract
Autoimmune hepatitis is an inflammatory disease of the liver of unknown cause that may progress to liver cirrhosis and end stage liver failure if diagnosis is overlooked and treatment delayed. The clinical presentation is often that of acute hepatitis, sometimes very severe; less frequently, it can be insidious or completely asymptomatic. The disease can affect people of any age and is more common in women; its incidence and prevalence seem to be on the rise worldwide. An abnormal immune response targeting liver autoantigens and inducing persistent and self-perpetuating liver inflammation is the pathogenic mechanism of the disease. A specific set of autoantibodies, increased IgG concentrations, and histological demonstration of interface hepatitis and periportal necrosis are the diagnostic hallmarks of autoimmune hepatitis. Prompt response to treatment with corticosteroids and other immunomodulatory drugs is almost universal and supports the diagnosis. The aims of treatment are to induce and maintain long term remission of liver inflammation. Treatment can often even reverse liver fibrosis, thus preventing progression to advanced cirrhosis and its complications. Most patients need lifelong maintenance therapy, and repeated follow-up in experienced hands improves the quality of care and quality of life for affected patients.
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Affiliation(s)
- Luigi Muratori
- DIMEC, Università di Bologna and IRCCS Policlinico di Sant'Orsola, Bologna, Italy
- European Reference Network for Hepatological Diseases (ERN RARE-LIVER)
| | - Ansgar W Lohse
- Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
- European Reference Network for Hepatological Diseases (ERN RARE-LIVER)
| | - Marco Lenzi
- DIMEC, Università di Bologna and IRCCS Policlinico di Sant'Orsola, Bologna, Italy
- European Reference Network for Hepatological Diseases (ERN RARE-LIVER)
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17
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Shi T, Malik A, Yang vom Hofe A, Matuschek L, Mullen M, Lages CS, Kudira R, Singh R, Zhang W, Setchell KD, Hildeman D, Pasare C, Wagner B, Miethke AG. Farnesoid X receptor antagonizes macrophage-dependent licensing of effector T lymphocytes and progression of sclerosing cholangitis. Sci Transl Med 2022; 14:eabi4354. [PMID: 36516265 PMCID: PMC9999117 DOI: 10.1126/scitranslmed.abi4354] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Immune-mediated bile duct epithelial injury and toxicity of retained hydrophobic bile acids drive disease progression in fibrosing cholangiopathies such as biliary atresia or primary sclerosing cholangitis. Emerging therapies include pharmacological agonists to farnesoid X receptor (FXR), the master regulator of hepatic synthesis, excretion, and intestinal reuptake of bile acids. Unraveling the mechanisms of action of pharmacological FXR agonists in the treatment of sclerosing cholangitis (SC), we found that intestinally restricted FXR activation effectively reduced bile acid pool size but did not improve the SC phenotype in MDR2-/- mice. In contrast, systemic FXR activation not only lowered bile acid synthesis but also suppressed proinflammatory cytokine production by liver-infiltrating inflammatory cells and blocked progression of hepatobiliary injury. The hepatoprotective activity was linked to suppressed production of IL1β and TNFα by hepatic macrophages and inhibition of TH1/TH17 lymphocyte polarization. Deletion of FXR in myeloid cells caused aberrant TH1 and TH17 lymphocyte responses in diethoxycarbonyl-1,4-dihydrocollidine-induced SC and rendered these mice resistant to the anti-inflammatory and liver protective effects of systemic FXR agonist treatment. Pharmacological FXR activation reduced IL1β and IFNγ production by liver- and blood-derived mononuclear cells from patients with fibrosing cholangiopathies. In conclusion, we demonstrate FXR to control the macrophage-TH1/17 axis, which is critically important for the progression of SC. Hepatic macrophages are cellular targets of systemic FXR agonist therapy for cholestatic liver disease.
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Affiliation(s)
- Tiffany Shi
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Astha Malik
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Annika Yang vom Hofe
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Louis Matuschek
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Mary Mullen
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Celine S. Lages
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Ramesh Kudira
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Ruchi Singh
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Wujuan Zhang
- Department of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Kenneth D.R. Setchell
- Department of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - David Hildeman
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
- Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Chandrashekhar Pasare
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
- Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | | | - Alexander G. Miethke
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
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18
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Autoimmune Hepatitis with Acute Presentation: Clinical, Biochemical, and Histological Features of 126 Patients. Can J Gastroenterol Hepatol 2022; 2022:6470847. [PMID: 36199980 PMCID: PMC9529506 DOI: 10.1155/2022/6470847] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 08/31/2022] [Accepted: 09/01/2022] [Indexed: 11/18/2022] Open
Abstract
INTRODUCTION Autoimmune hepatitis (AIH) is a chronic liver disease with a relevant inflammatory component and an unknown etiology. Evidence for clinical characteristics and risk factors in large cohorts of patients with acute AIH (AAIH) is lacking. We clinically characterized patients with AAIH, the prevalence of a combined adverse outcome (death or liver transplantation (LT)), and its risk factors. METHODS A retrospective study of adult patients diagnosed with AAIH at three centers (Santiago, Chile; 2000-2018) was conducted. Clinical and laboratory characteristics were obtained. A liver biopsy was performed for all patients. Descriptive statistics and logistic regression models were used. RESULTS A total of 126 patients were admitted; 77% were female, 33 (26.2%) had a severe presentation, and 14 (11.1%) had a fulminant presentation. Overall, 24 patients (19.0%) lacked typical autoantibodies, and 26.2% had immunoglobulin G levels in the normal range. The most frequent histological findings were plasma cells (86.5%), interface hepatitis (81.7%), and chronic hepatitis (81.0%). Rosettes were uncommon (35.6%). Advanced fibrosis was present in 27% of patients. Combined adverse outcomes occurred in 7.9% of cases, all fulminant with histological cholestasis. Alkaline phosphatase, bilirubin, and prothrombin less than 50% were independent risk factors for in-hospital death or LT (p value <0.05). Although corticosteroid treatment was associated with better outcomes (OR 0.095, p value = 0.013), more severe patients were less likely to receive this therapy. Discussion. In this large cohort of patients with AAIH, clinical characteristics differ from those reported in patients with chronic AIH. Fulminant hepatitis, histological cholestasis, alkaline phosphatase, bilirubin, and prothrombin were associated with death/LT.
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19
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Yang F, Zhou L, Shen Y, Zhao S, Zheng Y, Men R, Fan X, Yang L. Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis. Front Immunol 2022; 13:982186. [PMID: 35990653 PMCID: PMC9389112 DOI: 10.3389/fimmu.2022.982186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/15/2022] [Indexed: 11/16/2022] Open
Abstract
Autoimmune hepatitis (AIH) is an autoimmune disease caused by disruption of liver immune homeostasis. Genetic studies have revealed the predisposition of AIH with the human leukocyte antigen (HLA) region. Recently, metabolomics integrated with genomics has identified many genetic loci of biomedical interest. However, there is no related report in AIH. In the present study, we found that HLA-DRB1*04:05 was linked to the clinical features and prognosis of AIH in Chinese patients. Furthermore, our patients were divided into DRB1*04:05 positive and DRB1*04:05 negative groups and the metabolic profiling was done by HPLC/MS. We chose inosine, one of the highly altered metabolites, to explore the effect on an acute severe hepatitis murine model. The results showed that inosine treatment attenuated hepatocyte apoptosis, enhanced antioxidant ability and inhibited the activation and glycolysis of CD4+ T cell. We propose that inosine participates in the regulation of AIH through its protective effect on hepatocytes and inhibition of overactivated immune cells, which might provide a potential novel approach in treating acute form of AIH.
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Affiliation(s)
| | | | | | | | | | | | | | - Li Yang
- *Correspondence: Li Yang, ; Xiaoli Fan,
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20
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Duclos-Vallée JC, Debray D, De Martin E, Beux EL, Louvet A. Best practice guidelines for France regarding the diagnosis and management of autoimmune hepatitis. Clin Res Hepatol Gastroenterol 2022; 46:101871. [PMID: 35108657 DOI: 10.1016/j.clinre.2022.101871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/17/2022] [Accepted: 01/20/2022] [Indexed: 02/04/2023]
Affiliation(s)
- Jean-Charles Duclos-Vallée
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-Immunes, Villejuif, France.
| | - Dominique Debray
- Assistance Publique-Hôpitaux de Paris, University de Paris, Pediatric Liver Unit, Necker Hospital, Expert Center for Bile Duct Inflammatory Diseases and Autoimmune Hepatitis (FilFoie)
| | - Eleonora De Martin
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-Immunes, Villejuif, France
| | - Emilie Le Beux
- Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-Immunes, Saint-Antoine Hospital, Paris, France
| | - Alexandre Louvet
- Service des Maladies de l'Appareil Digestif, Hôpital Claude-Huriez, Lille University Hospital, France, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-Immunes (FilFoie)
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21
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Volchkova EA, Legkova KS, Topchy TB. COVID-19 as a trigger of autoimmune hepatitis. Case report. TERAPEVT ARKH 2022; 94:259-264. [DOI: 10.26442/00403660.2022.02.201374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 03/29/2022] [Indexed: 11/22/2022]
Abstract
Over the past two years, the entire medical community has taken up the fight against the new coronavirus infection. At the initial encounter with COVID-19, it seemed that this virus mainly affects the respiratory system. Still, with long-term observation, it turned out that the consequences of this disease can be much more severe and associated with lung damage and thromboembolic complications, and be a trigger for autoimmune diseases. According to the literature, after suffering COVID-19, some patients debuted systemic lupus erythematosus, hemolytic anemia, thrombocytopenia, developed GuillainBarr syndrome, vasculitis, and multiple sclerosis, and a case of autoimmune hepatitis (AIH) was described in foreign literature. AIH is a fairly rare disease, the prevalence of which in Europe is 1618 cases per 100 thousand inhabitants, affecting mainly women. It is known that chemicals and drugs (minocycline, diclofenac, methyldopa, infliximab, etanercept), viruses (HAV, HEV, EBV, HCV, CMV), environmental factors can serve as triggers of the autoimmune process in the liver. This article presents two clinical cases of AIH that developed after suffering a new coronavirus infection, which we consider as the initial provoking factor of autoimmune inflammation. Given the rarity of AIH, the description of new triggers is of clinical interest. It may be useful for doctors of different specialties since they faced drug-induced liver damage against the background of antiviral and immunobiological therapy. In the domestic literature, there have not yet been any publications devoted to the debut of AIH in adults after coronavirus infection.
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22
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COVID-19 vaccine and autoimmunity. A new case of autoimmune hepatitis and review of the literature. J Transl Autoimmun 2022; 5:100140. [PMID: 35013724 PMCID: PMC8730708 DOI: 10.1016/j.jtauto.2022.100140] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 01/02/2022] [Indexed: 12/19/2022] Open
Abstract
Autoimmunity following COVID-19 vaccination has been reported. Herein, a 79-year-old man with clinical and immunological features of autoimmune hepatitis type 1 after ChAdOx1 nCoV-19 vaccination is presented. Clinical manifestations rapidly remitted after the instauration of immunomodulatory management. This case, together with a comprehensive review of the literature, illustrates the association between COVID-19 vaccines and the development of autoimmune conditions.
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23
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Yang F, Fan X, Liu Y, Shen Y, Zhao S, Zheng Y, Men R, Xie Y, Yang L. Long Noncoding RNA and Circular RNA Expression Profiles of Monocyte-Derived Dendritic Cells in Autoimmune Hepatitis. Front Pharmacol 2021; 12:792138. [PMID: 34938195 PMCID: PMC8685411 DOI: 10.3389/fphar.2021.792138] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 11/16/2021] [Indexed: 02/05/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic liver disease caused by disruption of liver immune homeostasis. The effect of dendritic cells (DCs) on the pathogenesis of AIH is not fully understood. Long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) have been shown to play critical roles in the regulation of cell function. In this study, we analyzed the immunophenotypic characteristics of DCs in the peripheral blood. The percentage of mature DCs was higher in AIH patients than in healthy controls (HCs), and the proportion of mature DCs decreased after treatment. We isolated monocyte-derived DCs (moDCs) from the peripheral blood, obtained whole RNA-sequencing (RNA-seq) data for the moDCs from the two groups, and identified differentially expressed (DE) lncRNAs, circRNAs, miRNAs and mRNAs. In addition, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for the DE mRNAs and constructed competing endogenous RNA (ceRNA) networks. ENST00000543334, hsa_circ_0000279, and hsa_circ_0005076 were selected and validated by RT-qPCR. These results provide a possible molecular mechanism of DCs in the pathogenesis of AIH and identify some potential therapeutic targets.
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Affiliation(s)
- Fan Yang
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoli Fan
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Yifeng Liu
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Shen
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Shenglan Zhao
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Yanyi Zheng
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Ruoting Men
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Yan Xie
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Li Yang
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
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24
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Ter Avest MM, van Hee K, Bronkhorst C, de Jonge HJM. Mesalazine induced autoimmune hepatitis in a patient with Crohn's disease. Clin Res Hepatol Gastroenterol 2021; 45:101551. [PMID: 33158802 DOI: 10.1016/j.clinre.2020.09.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 09/20/2020] [Accepted: 09/28/2020] [Indexed: 02/04/2023]
Affiliation(s)
- Milou M Ter Avest
- Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, The Netherlands
| | - Koen van Hee
- Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, The Netherlands
| | | | - Hendrik J M de Jonge
- Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, The Netherlands.
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Domerecka W, Kowalska-Kępczyńska A, Michalak A, Homa-Mlak I, Mlak R, Cichoż-Lach H, Małecka-Massalska T. Etiopathogenesis and Diagnostic Strategies in Autoimmune Hepatitis. Diagnostics (Basel) 2021; 11:1418. [PMID: 34441353 PMCID: PMC8393562 DOI: 10.3390/diagnostics11081418] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 07/29/2021] [Accepted: 08/03/2021] [Indexed: 01/10/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic liver disease with the incidence of 10 to 17 per 100,000 people in Europe. It affects people of any age, but most often occurs in the 40-60 age group. The clinical picture is varied, from asymptomatic to severe acute hepatitis or liver failure. The disease onset is probably associated with the impaired function of T lymphocytes, the development of molecular mimicry, intestinal dysbiosis, or infiltration with low density neutrophils, which, alongside autoantibodies (i.e., ANA, ASMA), implicate the formation of neutrophil extracellular traps (NETs), as a component of the disease process, and mediate the inappropriate immune response. AIH is characterized with an increased activity of aminotransferases, elevated concentration of serum immunoglobulin G, the presence of circulating autoantibodies and liver inflammation. The result of the histological examination of the liver and the presence of autoantibodies, although not pathognomonic, still remain a distinguishing feature. The diagnosis of AIH determines lifelong treatment in most patients. The treatment is implemented to prevent the development of cirrhosis and end-stage liver failure. This work focuses mainly on the etiopathogenesis and diagnosis of AIH.
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Affiliation(s)
- Weronika Domerecka
- Chair and Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland; (I.H.-M.); (R.M.); (T.M.-M.)
| | - Anna Kowalska-Kępczyńska
- Department of Biochemical Diagnostics, Chair of Laboratory Diagnostics, Medical University of Lublin, 20-081 Lublin, Poland;
| | - Agata Michalak
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, 20-090 Lublin, Poland; (A.M.); (H.C.-L.)
| | - Iwona Homa-Mlak
- Chair and Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland; (I.H.-M.); (R.M.); (T.M.-M.)
| | - Radosław Mlak
- Chair and Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland; (I.H.-M.); (R.M.); (T.M.-M.)
| | - Halina Cichoż-Lach
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, 20-090 Lublin, Poland; (A.M.); (H.C.-L.)
| | - Teresa Małecka-Massalska
- Chair and Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland; (I.H.-M.); (R.M.); (T.M.-M.)
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HLA-DR Mismatch and Black Race Are Associated With Recurrent Autoimmune Hepatitis After Liver Transplantation. Transplant Direct 2021; 7:e714. [PMID: 34131586 PMCID: PMC8196096 DOI: 10.1097/txd.0000000000001160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 03/30/2021] [Indexed: 01/02/2023] Open
Abstract
Supplemental Digital Content is available in the text. The predictors of recurrent autoimmune hepatitis (R-AIH) after liver transplantation (LT) are heterogeneous with limited data to guide immunosuppression, with little data on impact of race.
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De Martin E, Coilly A, Chazouillères O, Roux O, Peron JM, Houssel-Debry P, Artru F, Silvain C, Ollivier-Hourmand I, Duvoux C, Heurgue A, Barge S, Ganne-Carrié N, Pageaux GP, Besch C, Bourlière M, Fontaine H, de Ledinghen V, Dumortier J, Conti F, Radenne S, Debette-Gratien M, Goria O, Durand F, Potier P, Di Martino V, Reboux N, Ichai P, Sebagh M, Mathurin P, Agostini H, Samuel D, Duclos-Vallée JC. Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score. J Hepatol 2021; 74:1325-1334. [PMID: 33503489 DOI: 10.1016/j.jhep.2020.12.033] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 12/08/2020] [Accepted: 12/22/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated. METHODS This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3-D0)/D0. RESULTS A total of 128 patients were included, with a median age of 52 (39-62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23-21.06; p <0.001), Δ%3-INR ≥0.1% (OR 6.97; 95% CI 1.59-30.46; p <0.01) and Δ%3-bilirubin ≥-8% (OR 5.14; 95% CI 1.09-24.28; p <0.04) were predictive of a non-response. The SURFASA score: -6.80+1.92∗(D0-INR)+1.94∗(Δ%3-INR)+1.64∗(Δ%3-bilirubin), created by combining these variables, was highly predictive of LT or death (AUC = 0.93) (88% specificity; 84% sensitivity) with a cut-off point of <-0.9. Below this cut-off, the chance of responding was 75%. With a score higher than 1.75, the risk of dying or being transplanted was between 85% and 100%. CONCLUSION In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort. LAY SUMMARY The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
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Affiliation(s)
- Eleonora De Martin
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France.
| | - Audrey Coilly
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France
| | - Olivier Chazouillères
- AP-HP Hôpital St Antoine, Université Pierre et Marie Curie Paris 6, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Service d'Hépato-Gastroentérologie, Paris, France
| | - Olivier Roux
- AP-HP Hôpital Beaujon, Centre de Références des Maladies Vasculaires du Foie, Service d'Hépatologie, Clichy, France
| | - Jean-Marie Peron
- Service d'Hépatologie, Hôpital Rangueil CHU Toulouse, Université Paul Sabatier III, Toulouse, France
| | - Pauline Houssel-Debry
- CHU de Rennes, Hôpital Pontchaillou, Service d'Hépatologie et Transplantation Hépatique, Rennes, France
| | - Florent Artru
- CHRU Lille, Hôpital Claude Huriez, Service des Maladies de l'Appareil Digestif, Lille, France
| | | | | | - Christophe Duvoux
- AP-HP Hôpital Henri-Mondor, Service d'Hépato-Gastroentérologie, Créteil, France
| | - Alexandra Heurgue
- CHU Reims Service Hépato-Gastro-Entérologie et Cancérologie Digestive, Reims, France
| | - Sandrine Barge
- Hôpital Saint Camille, Service Hépato-Gastro-entérologie, Bry-sur-Marne, France
| | | | - Georges-Philippe Pageaux
- CHU Saint-Eloi, Département d'Hépato-Gastroentérologie et de Transplantation Hépatique, Montpellier, France
| | - Camille Besch
- Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Service de Chirurgie Générale, Hépatique, Endocrinienne et Transplantation, Strasbourg, France
| | - Marc Bourlière
- Hôpital St Joseph, Service d'Hépato-Gastroentérologie, Marseille, France
| | - Hélène Fontaine
- AP-HP CHU Cochin, Service d'Hépatologie, Université Paris Descartes, INSERM U-818 et USM20, Institut Pasteur, Paris, France
| | | | - Jérôme Dumortier
- Hospices Civils de Lyon, Hôpital édouard Herriot, Fédération des Spécialités Digestives, et Université de Lyon, Lyon, France
| | - Filomena Conti
- AP-HP Hôpital de la Pitié Salpêtrière, Service de Transplantation Hépatique, Paris, France
| | - Sylvie Radenne
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service d'Hépato-Gastroentérologie, Lyon, France
| | | | - Odile Goria
- CHU Rouen, Service d'Hépato-gastroentérologie, Rouen, France
| | - François Durand
- AP-HP Hôpital Beaujon, Centre de Références des Maladies Vasculaires du Foie, Service d'Hépatologie, Clichy, France
| | - Pascal Potier
- CHR d'Orléans, Service d'Hépato-Gastro-entérologie et Oncologie Digestive, Orléans, France
| | | | - Noemi Reboux
- Hôpital La Cavale Blanche, Service d'Hépato-Gastroentérologie, Brest, France
| | - Philippe Ichai
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France
| | - Mylène Sebagh
- AP-HP Hôpital du Kremlin-Bicêtre, Service Anatomie et Cytologie Pathologiques, Le Kremlin-Bicêtre, France
| | - Philippe Mathurin
- CHRU Lille, Hôpital Claude Huriez, Service des Maladies de l'Appareil Digestif, Lille, France
| | - Hélène Agostini
- AP-HP Paris Saclay, Unité de Recherche Clinique des Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France
| | - Jean-Charles Duclos-Vallée
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France.
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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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Muratori P, Granito A, Lenzi M, Muratori L. Limitation of the simplified scoring system for the diagnosis of autoimmune Hepatitis with acute onset. Liver Int 2021; 41:529-534. [PMID: 33389800 DOI: 10.1111/liv.14778] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/14/2020] [Accepted: 12/28/2020] [Indexed: 12/18/2022]
Abstract
Autoimmune Hepatitis (AIH) is a chronic inflammatory liver disease of unknown aetiology characterized by the presence of autoantibodies, hypergammaglobulinaemia with specific IgG increase and interface hepatitis on liver histology. The clinical course of AIH is classically characterized by fluctuating periods of decreased or increased disease activity and therefore its clinical spectrum is variable ranging from no symptoms to severe acute hepatitis and even fulminant hepatic failure. Acute presentation may not differ from acute hepatitis of other causes and diagnosis can be difficult. We describe our experience on diagnostic performance of the two AIH scoring systems in acute onset of AIH and found that revised version of the original criteria (1999) achieves the diagnosis in about 30% of patients who presented with normal IgG serum levels and lower frequency of autoantibody positivity in whom the simplified score did not allow the diagnosis.
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Affiliation(s)
- Paolo Muratori
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna, Italy
- Department of Science for the Quality of Life, University of Bologna, Bologna, Italy
| | - Alessandro Granito
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna, Italy
- Department of Medicine and Surgery, University of Bologna, Bologna, Italy
| | - Marco Lenzi
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna, Italy
- Department of Medicine and Surgery, University of Bologna, Bologna, Italy
| | - Luigi Muratori
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna, Italy
- Department of Medicine and Surgery, University of Bologna, Bologna, Italy
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30
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Rahim MN, Miquel R, Heneghan MA. Approach to the patient with acute severe autoimmune hepatitis. JHEP Rep 2020; 2:100149. [PMID: 32995712 PMCID: PMC7509236 DOI: 10.1016/j.jhepr.2020.100149] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 07/09/2020] [Accepted: 07/15/2020] [Indexed: 12/11/2022] Open
Abstract
Autoimmune hepatitis is associated with varied clinical presentations and natural history, as well as somewhat unpredictable treatment responses. Understanding how to stratify patients who require further escalation of therapy will help clinicians manage these patients. The presentation of acute severe autoimmune hepatitis (AS-AIH) is relatively uncommon, although its prevalence is potentially greater than currently perceived. Previous studies consist of small retrospective single-centre series and are not directly comparable due to the diversity of presentations, disease definitions and non-standardised treatment regimens. We define AS-AIH as those who present acutely with AIH and are icteric with an international normalised ratio ≥1.5 and no evidence of hepatic encephalopathy. Those with hepatic encephalopathy should be defined as having AS-AIH with acute liver failure. In this review, we provide a structured practical approach for diagnosing and managing this unique group of patients.
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Key Words
- ACLF, acute-on-chronic liver failure
- AIH, autoimmune hepatitis
- ALF, acute liver failure
- ALI, acute liver injury
- ALT, alanine aminotransferase
- ANA, anti-nuclear antibody
- AS-AIH, acute severe autoimmune hepatitis
- ASMA, anti-smooth muscle antibody
- AST, aspartate aminotransferase
- AUROC, analysis of area under the receiver operator characteristic curve
- Acute liver failure
- Acute severe presentation
- Autoimmune hepatitis
- CT, computed tomography
- Corticosteroids
- DILI, drug-induced liver injury
- EBV, Epstein-Barr virus
- HE, hepatic encephalopathy
- HLA, human leukocyte antigen
- IAIHG, International Autoimmune Hepatitis Group
- INR, international normalised ratio
- LT, liver transplantation
- Liver transplantation
- MELD, model for end-stage liver disease
- MELD-Na, model for end-stage liver disease-sodium
- MHN, massive hepatic necrosis
- NAC, N-acetylcysteine
- PT, prothrombin time
- UKELD, United Kingdom end-stage liver disease
- USALF, United States Acute Liver Failure
- anti-LC-1, anti-liver cytosol-1
- anti-LKM, anti-liver kidney microsomal
- anti-SLA/LP, anti-soluble liver antigen/liver pancreas
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Affiliation(s)
- Mussarat N. Rahim
- Institute of Liver Studies, King's College Hospital, London, SE5 9RS, UK
| | - Rosa Miquel
- Liver Histopathology Laboratory, King's College Hospital, London, SE5 9RS, UK
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Wang H, Feng X, Yan W, Tian D. Regulatory T Cells in Autoimmune Hepatitis: Unveiling Their Roles in Mouse Models and Patients. Front Immunol 2020; 11:575572. [PMID: 33117375 PMCID: PMC7575771 DOI: 10.3389/fimmu.2020.575572] [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: 06/23/2020] [Accepted: 09/07/2020] [Indexed: 12/11/2022] Open
Abstract
Autoimmune hepatitis (AIH) is a severe and chronic liver disease, and its incidence has increased worldwide in recent years. Research into the pathogenesis of AIH remains limited largely owing to the lack of suitable mouse models. The concanavalin A (ConA) mouse model is a typical and well-established model used to investigate T cell-dependent liver injury. However, ConA-induced hepatitis is acute and usually disappears after 48 h; thus, it does not mimic the pathogenesis of AIH in the human body. Several studies have explored various AIH mouse models, but as yet there is no widely accepted and valid mouse model for AIH. Immunosuppression is the standard clinical therapy for AIH, but patient side effects and recurrence limit its use. Regulatory T cells (Tregs) play critical roles in the maintenance of immune homeostasis and in the prevention of autoimmune diseases, which may provide a potential therapeutic target for AIH therapy. However, the role of Tregs in AIH has not yet been clarified, partly because of difficulties in diagnosing AIH and in collecting patient samples. In this review, we discuss the studies related to Treg in various AIH mouse models and patients with AIH and provide some novel insights for this research area.
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Affiliation(s)
- Han Wang
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xinxia Feng
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Yan
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dean Tian
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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32
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Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease, characterized by the elevation of aminotransferases, presence of anti-nuclear antibody or anti-smooth muscle antibody, elevated immunoglobulin G (IgG), and interface hepatitis/plasma-lymphocytic inflammation based on histology. Recent epidemiological studies have indicated an increasing trend in the prevalence of AIH worldwide, especially in male patients; this trend may suggest the alteration of environmental triggers of disease onset over time. As no disease-specific biomarker or histological finding is currently available, AIH requires a clinical diagnosis, and a validated diagnostic scoring system with acceptable specificity and sensitivity has been proposed. Regarding treatment, corticosteroids and azathioprine are recommended, and in those who exhibit an incomplete response or those who are intolerant to these drugs, second-line therapy, such as mycophenolate mofetil, is considered. Overall, the long-term outcome is excellent in patients with complete biochemical responses, while life-long maintenance treatment may be required since the cessation of immunosuppressive agents frequently leads to the relapse of the disease. Acute-onset AIH does occur, and the diagnosis is very challenging due to the lack of serum autoantibodies or elevated IgG. The unmet needs include earlier diagnosis, intervention with disseminated clinical practice guidelines, and recognition and improvement of patients’ health-related quality of life with the development of novel corticosteroid-free treatment regimens.
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Affiliation(s)
- Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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33
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Liukkonen V, Nordin A, Arola J, Färkkilä M, Åberg F. Role of Autoimmunity in Patients Transplanted for Acute Liver Failure of Unknown Origin: A Clinical and Graft Biopsy Analysis. Liver Transpl 2020; 26:764-773. [PMID: 32034878 DOI: 10.1002/lt.25729] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Accepted: 01/28/2020] [Indexed: 12/14/2022]
Abstract
The etiology and prognosis of acute liver failure (ALF) remains unknown in a significant proportion of cases. Signs of autoimmunity may be present, but no consistent pattern has been observed. We aimed to analyze if pretransplant immunological findings, human leukocyte antigen (HLA) haplotypes, and clinical features among patients with an unknown etiology differ from those of autoimmune or other known etiologies. We also analyzed whether such signs impact posttransplant biopsy findings or complications. All adult ALF patients undergoing liver transplantation (LT) in Finland during 1987-2015 were followed to 2016. Data were collected from the LT registry, pathology database, and patient records. A total of 124 patients were included in the analysis. Study subgroups were acute autoimmune hepatitis (AIH; n = 25), known non-AIH etiology (n = 54), and unknown etiology (n = 45). The unknown etiology group differed from the known non-AIH group with regard to the following pretransplant autoimmunity-associated features: positive perinuclear anti-neutrophil cytoplasmic antibodies (36% versus 8%; P = 0.02) and higher mean immunoglobulin A (IgA; 3.2 ± 1.7 versus 2.1 ± 1.4, P = 0.006) and immunoglobulin G (IgG; 12.7 ± 4.3 versus 8.5 ± 3.6, P = 0.001). AIH-associated HLA haplotypes B8, DR3, and B8DR3 were more common in the AIH group (40%, 44%, and 36%, respectively) and in the unknown group (29%, 33%, and 29%, respectively) than in the known non-AIH group (11%, 17%, and 11%, respectively) or in the Finnish general population (17%, 18%, and 8%, respectively). However, these findings had no association with protocol biopsies, extrahepatic autoimmune diseases, or survival. Patients with ≥ 1 rejection episode had higher pretransplant IgA (3.7 ± 2.3 versus 2.6 ± 1.2; P = 0.02) and IgG (16.4 ± 10.2 versus 12.4 ± 6.8; P = 0.03) than those without rejections. Autoimmunity-associated pretransplant laboratory findings and HLA haplotypes were common in ALF of unknown etiology, but they showed minimal predictive value for posttransplant biopsy findings, clinical complications, or survival.
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Affiliation(s)
- Ville Liukkonen
- Department of Gastroenterology, Helsinki University Hospital, Helsinki, Finland
| | - Arno Nordin
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
| | - Johanna Arola
- Department of Pathology, Laboratory of Helsinki University Hospital (HUSLAB), University of Helsinki, Helsinki, Finland
| | - Martti Färkkilä
- Department of Gastroenterology, Helsinki University Hospital, Helsinki, Finland
| | - Fredrik Åberg
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
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34
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Ikura A, Chu PS, Nakamoto N, Ojiro K, Taniki N, Yoshida A, Shinoda M, Morikawa R, Yamataka K, Noguchi F, Hoshi H, Usui S, Ebinuma H, Kitagawa Y, Saito H, Kanai T. CLIF-C Organ Failure Score and Liver Volume Predict Prognosis in Steroid-Treated Severe Acute Autoimmune Hepatitis. Hepatol Commun 2020; 4:1019-1033. [PMID: 32626834 PMCID: PMC7327221 DOI: 10.1002/hep4.1521] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 03/11/2020] [Accepted: 04/02/2020] [Indexed: 12/19/2022] Open
Abstract
Controversies and debates remain regarding the best management of severe acute‐onset autoimmune hepatitis (SA‐AIH) due to the lack of useful outcome or complication prediction systems. We conducted this clinical practice‐based observational study to clarify whether Chronic Liver Failure Consortium Organ Failure scores (CLIF‐C OFs) and the computed tomography–derived liver volume to standard liver volume (CTLV/SLV) ratio at admission to a tertiary transplant center can predict outcomes and complications due to infection. Thirty‐four consecutive corticosteroid‐treated patients with SA‐AIH from 2007 to 2018 were included. Severe hepatitis was defined as an international normalized ratio (of prothrombin time) over 1.3 any time before admission. Of the 34 corticosteroid‐treated patients with SA‐AIH inclusive of 25 (73.5%) acute liver failure cases, transplant‐free survival was observed in 24 patients (70.6%). Any infection was noticed in 10 patients (29.4%). CLIF‐C OFs, at the cutoff of 9, significantly predicted survival (P = 0.0002, log‐rank test), outperformed the Model for End‐stage Liver Disease system in predicting outcome (P = 0.0325), and significantly discriminated between liver transplant and death in a competing risk analysis. SA‐AIH was characterized as having decreased CTLV/SLV, which was also predictive of survival (P < 0.0001). Interestingly, CLIF‐C OFs, especially the subscores for respiratory dysfunction, also predicted infection (P = 0.007). Conclusion: In corticosteroid‐treated patients with SA‐AIH, CLIF‐C OFs and CTLV/SLV ratios predicted both survival outcome and complications due to infection. Further investigation is warranted to determine whether making decisions based on CLIF‐C OFs or CTLV/SLV ratios is useful.
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Affiliation(s)
- Akihiko Ikura
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Po-Sung Chu
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Nobuhiro Nakamoto
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Keisuke Ojiro
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan.,Department of Gastroenterology and Hepatology Tokyo Dental College Ichikawa General Hospital Ichikawa City Japan
| | - Nobuhito Taniki
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Aya Yoshida
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Masahiro Shinoda
- Department of Surgery Keio University School of Medicine Tokyo Japan
| | - Rei Morikawa
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Karin Yamataka
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Fumie Noguchi
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Hitomi Hoshi
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Shingo Usui
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan.,Department of Gastroenterology and Hepatology National Hospital Organization Saitama Hospital Wako City Japan
| | - Hirotoshi Ebinuma
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan.,Department of Gastroenterology International University of Health and Welfare School of Medicine Narita City Japan
| | - Yuko Kitagawa
- Department of Surgery Keio University School of Medicine Tokyo Japan
| | - Hidetsugu Saito
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan.,Division of Pharmacotherapeutics Keio University School of Pharmacy Tokyo Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan
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35
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Fan X, Men R, Huang C, Shen M, Wang T, Ghnewa Y, Ma Y, Ye T, Yang L. Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation. Cell Death Dis 2020; 11:23. [PMID: 31932577 PMCID: PMC6957703 DOI: 10.1038/s41419-019-2217-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 12/10/2019] [Accepted: 12/11/2019] [Indexed: 02/05/2023]
Abstract
Autoimmune hepatitis (AIH) is a necroinflammatory disease associated with interactive cell populations of the innate and adaptive immune systems. The contribution of conventional dendritic cells (cDCs) to AIH and the underlying mechanism remain poorly understood. The frequency of peripheral mature cDCs increased in AIH patients and was positively correlated with disease severity. In experimental autoimmune hepatitis (EAH), hepatic accumulation of mature cDCs was observed, along with an increase in the periphery. Sequentially, bone marrow-derived dendritic cells (BMDC) from EAH mice exhibit more proinflammatory function than those from control mice. In vitro, ConA treatment promotes the maturation of BMDCs, which are characterized by higher expression of MHC-II, costimulatory molecules and cytokine secretion. ConA also induced the expression of autophagy-related protein and the formation of autophagosomes in DCs. To further investigate whether ConA-induced DC activation is associated with autophagy, we utilized 3-MA and bafilomycin A1 to block autophagy flux and accessed the maturation and function of DCs induced by ConA. 3-MA and bafilomycin A1 inhibited the mature status and proinflammatory cytokine secretion and diminished the proliferation and differentiation of CD4+ T cells when ConA-induced BMDCs cocultured CD4+ T cells. We demonstrated that cDCs contribute to the pathogenesis of AIH through excessive maturation. Aberrant autophagy flux plays a vital role in the immunogenic maturation of cDCs in AIH, and tolerogenic cDCs by inhibition of autophagy flux can be exploited as a new therapeutic approach for AIH.
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Affiliation(s)
- Xiaoli Fan
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Ruoting Men
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Chen Huang
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Mengyi Shen
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Tingting Wang
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Yasmeen Ghnewa
- Institute of Liver Studies, King's College London Faculty of Life Sciences and Medicine at King's College Hospital, London, UK
| | - Yun Ma
- Institute of Liver Studies, King's College London Faculty of Life Sciences and Medicine at King's College Hospital, London, UK
| | - Tinghong Ye
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
| | - Li Yang
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, China.
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36
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Autoimmune Hepatitis-Immunologically Triggered Liver Pathogenesis-Diagnostic and Therapeutic Strategies. J Immunol Res 2019; 2019:9437043. [PMID: 31886312 PMCID: PMC6899271 DOI: 10.1155/2019/9437043] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 09/15/2019] [Accepted: 09/21/2019] [Indexed: 12/20/2022] Open
Abstract
Autoimmune hepatitis (AIH) is a severe liver disease that arises in genetically predisposed male and female individuals worldwide. Diagnosis of AIH is made clinically applying diagnostic scores; however, the heterotopic disease phenotype often makes a rapid determination of disease challenging. AIH responds favorably to steroids and pharmacologic immunosuppression, and liver transplantation is only necessary in cases with acute liver failure or end-stage liver cirrhosis. Recurrence or development of de novo AIH after transplantation is possible, and treatment is similar to standard AIH therapy. Current experimental investigations of T cell-mediated autoimmune pathways and analysis of changes within the intestinal microbiome might advance our knowledge on the pathogenesis of AIH and trigger a spark of hope for novel therapeutic strategies.
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Arcos-Machancoses JV, Molera Busoms C, Julio Tatis E, Bovo MV, Quintero Bernabeu J, Juampérez Goñi J, Crujeiras Martínez V, Martín de Carpi J. Development and validation of a new simplified diagnostic scoring system for pediatric autoimmune hepatitis. Dig Liver Dis 2019; 51:1308-1313. [PMID: 30928421 DOI: 10.1016/j.dld.2019.02.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 02/25/2019] [Accepted: 02/25/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Children with autoimmune hepatitis (AIH) often exhibit particular features. Accordingly, seven pediatric-specific criteria have been proposed. AIM To develop a prediction model based on them, transform it into a scoring system and study its accuracy. METHODS A cohort of children under study for liver disease was consecutively selected. AIH diagnosis was based on classical criteria. Already proposed pediatric criteria were recorded. The best possible regression model was selected, and the beta coefficient of each criterion was translated into a whole number (points). Total scores were obtained following the points system and the best cut-off was calculated. Subsequently, accuracy of the diagnostic score was studied in the validation set. RESULTS Among 212 included patients, 100 had AIH. The score included 5 criteria: autoantibodies (0-2 points), hypergammaglobulinemia, exclusion of viral hepatitis, exclusion of Wilson's disease (1 point each) and liver histology (3 points). In addition, a normal cholangiogram is mandatory. The validation set was formed of 70 patients (24 with AIH). In this subsample, a score of ≥6 renders a sensitivity/specificity of 95.8%/100%. The area under the receiver operating characteristic curve was 97.1%. CONCLUSION Pediatric-specific criteria for the diagnosis of AIH can be reliably used as a scoring system.
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Affiliation(s)
| | - Cristina Molera Busoms
- Sant Joan de Déu Hospital (HSJD), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain; HSJD-HVH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain.
| | - Ecaterina Julio Tatis
- Sant Joan de Déu Hospital (HSJD), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain.
| | - María Victoria Bovo
- Sant Joan de Déu Hospital (HSJD), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain.
| | - Jesús Quintero Bernabeu
- Vall d'Hebron Hospital (HVH), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain; HSJD-HVH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain.
| | - Javier Juampérez Goñi
- Vall d'Hebron Hospital (HVH), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain; HSJD-HVH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain.
| | - Vanessa Crujeiras Martínez
- University Hospital Complex of Santiago de Compostela, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Spain.
| | - Javier Martín de Carpi
- Sant Joan de Déu Hospital (HSJD), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain; HSJD-HVH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain.
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38
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Sano A, Inoue J, Kakazu E, Ninomiya M, Iwata T, Morosawa T, Takai S, Nakamura T, Masamune A. Acute-onset Autoimmune Hepatitis in a Patient with Selective Immunoglobulin M Deficiency. Intern Med 2019; 58:2185-2190. [PMID: 30996186 PMCID: PMC6709322 DOI: 10.2169/internalmedicine.2607-18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Selective immunoglobulin M deficiency (SIGMD) is an uncommon primary immunodeficiency disorder. We herein report an SIGMD patient with autoimmune hepatitis. A 21-year-old Japanese man was transferred to our hospital because of acute liver dysfunction. His serum IgM level was low, whereas those of IgG and IgA were normal, indicating that he had SIGMD. We diagnosed him with acute-onset autoimmune hepatitis, and his liver function test findings gradually recovered with corticosteroid administration. Although SIGMD with autoimmune diseases has been reported, the clinical features and pathogenesis have not yet been clarified. We have summarized previous reports on SIGMD patients with autoimmune diseases.
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Affiliation(s)
- Akitoshi Sano
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Jun Inoue
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Eiji Kakazu
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Masashi Ninomiya
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Tomoaki Iwata
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | | | - Satoshi Takai
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Takuya Nakamura
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
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39
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Rahim MN, Liberal R, Miquel R, Heaton ND, Heneghan MA. Acute Severe Autoimmune Hepatitis: Corticosteroids or Liver Transplantation? Liver Transpl 2019; 25:946-959. [PMID: 30900368 DOI: 10.1002/lt.25451] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 03/17/2019] [Indexed: 12/13/2022]
Abstract
Acute severe presentations of autoimmune hepatitis (AIH) represent a challenge for the transplant community. As a disease, it is poorly characterized, and there is a weak evidence base to guide diagnosis and treatment. Early identification of acute severe AIH is key because it determines the initiation of corticosteroids, which can be lifesaving. However, their use in this setting remains controversial. The Model for End-Stage Liver Disease score, severity of coagulopathy, and grade of encephalopathy may be predictors of outcome with corticosteroid therapy. The optimal timing of liver transplantation (LT) can be difficult to determine and, as such, the decision to proceed to transplantation should not be delayed by protracted courses of corticosteroids. The aim of this review is to better characterize this subset of patients; to differentiate them clinically, serologically, and histologically from chronic AIH and other causes of acute liver failure; and to present the role, predictors, and optimal timings of corticosteroid therapy and LT. Although this review is specific to adults, many principles hold true for the pediatric population.
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Affiliation(s)
- Mussarat N Rahim
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
| | - Rodrigo Liberal
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
| | - Rosa Miquel
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
| | - Nigel D Heaton
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
| | - Michael A Heneghan
- Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom
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40
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Dyson JK, De Martin E, Dalekos GN, Drenth JPH, Herkel J, Hubscher SG, Kelly D, Lenzi M, Milkiewicz P, Oo YH, Heneghan MA, Lohse AW. Review article: unanswered clinical and research questions in autoimmune hepatitis-conclusions of the International Autoimmune Hepatitis Group Research Workshop. Aliment Pharmacol Ther 2019; 49:528-536. [PMID: 30671977 DOI: 10.1111/apt.15111] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 06/29/2018] [Accepted: 12/04/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that results in substantial morbidity and mortality with many unanswered clinical and research questions. Improved understanding of disease pathogenesis, including the extra-hepatic manifestations of AIH, may allow targeted treatments with greater efficacy and fewer associated adverse events. AIM To identify the spectrum of unanswered clinical and research questions facing care providers in the management of patients with autoimmune hepatitis (AIH). METHODS The International Autoimmune Hepatitis Group initiated a series of research workshops to start to address these questions. Key issues were discussed in small group sessions with collation of all discussions to be summarised in this manuscript. RESULTS Key issues were identified as: the need for better understanding of disease pathogenesis, standardisation of the methods and assays used to evaluate autoantibodies in AIH, refinement of the histopathological criteria for "typical" or "compatible" AIH, focus on the interaction with non-alcohol related fatty liver disease, how to treat acute severe AIH, better assessment of quality of life in adults and paediatrics, standardising use of standard, third-line and experimental therapies in AIH and search for biomarkers early in the disease course that predict outcome. CONCLUSION This workshop has outlined the key unanswered clinical and research questions to help to define the research agenda in AIH.
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41
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Arcos-Machancoses JV, Molera Busoms C, Julio Tatis E, Bovo MV, Martín de Carpi J. Accuracy of the Simplified Criteria for Autoimmune Hepatitis in Children: Systematic Review and Decision Analysis. J Clin Exp Hepatol 2019; 9:147-155. [PMID: 31024195 PMCID: PMC6477136 DOI: 10.1016/j.jceh.2018.10.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 10/30/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/OBJECTIVES Several studies have been conducted on the accuracy of simplified criteria for autoimmune hepatitis that were presented in 2008 as an alternative to original criteria. Our purpose is to summarize the evidence available regarding their accuracy in children and to carry out a basic clinical decision analysis based on it. METHODS Electronic and manual searches were performed with keywords related to diagnostic validity terms. Data from included studies were extracted, and summary estimates of accuracy measures were calculated. An effect model was chosen depending on heterogeneity, and the presence of publication bias was also studied. Therapeutic threshold was calculated based on the already published data. Through a Bayesian approach, simplified criteria's clinical utility was simulated, taking into account the meta-analyzed indicators and several assumptions on the prevalence of autoimmune hepatitis. RESULTS The search yielded 166 studies, four of which were finally included, providing a total population of 437 patients. Pooled sensitivity and specificity of the simplified criteria for the diagnosis of autoimmune hepatitis in children was 77% and 95%, respectively, with a diagnostic odds ratio of 67. No evidence of publication bias was found. For prevalences ranging from 8.5 to 85.7, the predictive value of either a positive or a negative result moved beyond the therapeutic threshold (estimated at 56%). CONCLUSIONS The simplified criteria show high specificity and moderate sensitivity for the diagnosis of autoimmune hepatitis in children. A positive result can justify starting a therapeutic assay, but a negative result does not seem sufficient to rule out this condition.
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Affiliation(s)
- José V. Arcos-Machancoses
- Address for correspondence: J. V. Arcos-Machancoses, Sant Joan de Déu Hospital, Barcelona. Department of Pediatric Gastroenterology, Hepatology and Nutrition. Passeig de Sant Joan de Déu, 2, 08950 Esplugues de Llobregat, Barcelona (Catalonia), Spain.
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42
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Dalekos GN, Koskinas J, Papatheodoridis GV. Hellenic Association for the Study of the Liver Clinical Practice Guidelines: Autoimmune hepatitis. Ann Gastroenterol 2019; 32:1-23. [PMID: 30598587 PMCID: PMC6302199 DOI: 10.20524/aog.2018.0330] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Accepted: 10/29/2018] [Indexed: 02/07/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a relatively rare acute or chronic liver disease of unknown etiology characterized by large heterogeneity. Its distribution is global, covering all ages, both sexes and all ethnic groups. The aim of the present Clinical Practice Guidelines (CPG) of the Hellenic Association for the Study of the Liver was to provide updated guidance and help to gastroenterologists, hepatologists, internists and general practitioners for AIH diagnosis and management. AIH diagnosis is based on clinicopathological characteristics: namely, polyclonal hypergammaglobulinemia, particularly of immunoglobulin G (IgG), circulating autoantibodies, interface hepatitis on liver histology, absence of viral hepatitis, and a favorable response to immunosuppression. Clinical manifestations at disease onset are variable, ranging from asymptomatic to the acute/severe form. Aminotransferase and bilirubin levels vary, while the presence of hepatitis at the histological level is a prerequisite for diagnosis. Autoantibodies are the hallmark for AIH diagnosis; therefore, the CPG describe the appropriate serological algorithm for their detection. AIH therapy should aim to achieve complete biochemical (normalization of IgG and aminotransferases) and histological remission. All patients who have active disease, even those with cirrhosis, should be treated with individualized and response-guided induction therapy using prednisolone in combination with azathioprine or mycophenolate mofetil as first-line therapy. Immunosuppression should be given for at least 3 years and for at least 2 years after the achievement of complete biochemical response, while a liver biopsy should be recommended before treatment discontinuation. Current CPG are also provided for several specific conditions and difficult-to-treat patients.
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Affiliation(s)
- George N. Dalekos
- Institute of Internal Medicine and Hepatology, Larissa (George N. Dalekos)
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa (George N. Dalekos)
| | - John Koskinas
- Second Department of Internal Medicine, National and Kapodistrian University of Athens, “Hippokratio” General Hospital of Athens, Athens (John Koskinas)
| | - George V. Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, “Laiko” General Hospital of Athens, Athens (George V. Papatheodoridis), Greece
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43
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Zachou K, Arvaniti P, Azariadis K, Lygoura V, Gatselis NK, Lyberopoulou A, Koukoulis GK, Dalekos GN. Prompt initiation of high-dose i.v. corticosteroids seems to prevent progression to liver failure in patients with original acute severe autoimmune hepatitis. Hepatol Res 2019; 49:96-104. [PMID: 30248210 DOI: 10.1111/hepr.13252] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 09/14/2018] [Accepted: 09/19/2018] [Indexed: 12/20/2022]
Affiliation(s)
- Kalliopi Zachou
- Institute of Internal Medicine and Hepatology, Larissa, Greece.,Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa, Greece
| | - Pinelopi Arvaniti
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa, Greece
| | - Kalliopi Azariadis
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa, Greece
| | - Vasiliki Lygoura
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 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, Larissa, Greece
| | - Aggeliki Lyberopoulou
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa, Greece
| | - George K Koukoulis
- Department of Pathology, Medical School, University of Thessaly, Larissa, Greece
| | - George N Dalekos
- Institute of Internal Medicine and Hepatology, Larissa, Greece.,Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa, Greece
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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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45
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Christen U, Hintermann E. Pathogens and autoimmune hepatitis. Clin Exp Immunol 2018; 195:35-51. [PMID: 30113082 DOI: 10.1111/cei.13203] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 07/30/2018] [Accepted: 08/06/2018] [Indexed: 12/12/2022] Open
Abstract
Autoimmune hepatitis (AIH) is a severe form of hepatitis resulting in the autoimmune-mediated destruction of the liver parenchyma. Whereas many of the immunopathogenic events have been elucidated and some of the drivers of the disease have been identified, little is known about the aetiology of the disease. There are certain risk factors, such as particular human leucocyte antigen (HLA) haplotypes, that enhance the susceptibility for AIH or influence the severity of the disease. However, as for many other autoimmune diseases, the mere presence of such risk factors does not warrant the occurrence of the disease. Not all individuals carrying risk factors develop AIH, and not all patients with AIH are carriers of high-risk alleles. Thus, additional environmental factors need to be considered as triggers for AIH. Environmental factors include diet, sunlight exposure, stress, medication and hygiene, as well as pathogen infections and vaccinations. This review discusses if pathogens should be considered as triggers for the initiation and/or propagation of AIH.
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Affiliation(s)
- U Christen
- Pharmazentrum Frankfurt / ZAFES, Goethe University Hospital, Frankfurt am Main, Germany
| | - E Hintermann
- Pharmazentrum Frankfurt / ZAFES, Goethe University Hospital, Frankfurt am Main, Germany
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Gordon V, Adhikary R, Appleby V, Das D, Day J, Delahooke T, Dixon S, Elphick D, Hardie C, Hoeroldt B, Hooper P, Hutchinson J, Jones R, Khan F, Aithal GP, McGonigle J, Nelson A, Nkhoma A, Pelitari S, Prince M, Prosser A, Sathanarayana V, Savva S, Shah N, Saksena S, Thayalasekaran S, Vani D, Yeoman A, Gleeson D. Diagnosis, presentation and initial severity of Autoimmune Hepatitis (AIH) in patients attending 28 hospitals in the UK. Liver Int 2018; 38:1686-1695. [PMID: 29455458 DOI: 10.1111/liv.13724] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2017] [Accepted: 02/04/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS There is limited information regarding patients with AIH outside relatively few large centres. We describe here the presenting features of patients with AIH, collected as part of an audit involving 28 UK hospitals. METHODS Patients (incident since 1/1/2007 or prevalent since 1/1/2000) were ≥18 years and either met 1999 International AIH Group (IAIHG) diagnostic criteria (n = 1164), or received immunosuppressive therapy for clinically diagnosed AIH (n = 103). RESULTS Of 1267 patients (80% women, 91% Caucasian, age (median(range)) 55(8-86) years, 0.5% had acute viral hepatitis (CMV/EBV/HEV); 2% were taking Nitrofurantoin and 0.7% Khat. Twenty-one percent had clinical decompensation and/or a MELD score of >15. Time from first abnormal liver tests to diagnosis was ≥1 year in 19% and was longer in jaundiced vs non-jaundiced patients. HBV and HCV serology were undocumented in 4%, serum immunoglobulins in 31% and autoantibodies in 11%-27%. When documented, ≥1 antibody was present in 83%. LKM-1-positive and autoantibody-negative patients had more severe disease. Histological cirrhosis was reported in 23%, interface hepatitis 88%, predominant lymphocytes/plasma cells 75%, rosettes 19% and emperipolesis 0.4%. Only 65% of those meeting 1999 IAIHG criteria also met simplified IAIHG criteria. University Hospitals compared to District General Hospitals, were more likely to report histological features of AIH. CONCLUSIONS This cohort from across the UK is older than other multicentre AIH cohorts. One-fifth had decompensation or MELD >15. Diagnosis was delayed in 19%, diagnostic testing was incomplete in one-third and rosettes and emperipolesis were infrequently reported.
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Affiliation(s)
- Victoria Gordon
- Sheffield Teaching Hospitals Foundation NHS Trust, Sheffield, UK
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - Guruprasad P Aithal
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - Dermot Gleeson
- Sheffield Teaching Hospitals Foundation NHS Trust, Sheffield, UK
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47
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Tikhonov IN, Zharkova MS, Maevskaya MV, Zozulya VN, Nekrasova TP, Arslanyan MG, Musina NP, Tatarkina MA, Rzaev RT, Puzakov KB, Ivashkin VT, Malikova MS. Differential diagnosis of ascites in internal medicine: clinical case. TERAPEVT ARKH 2018; 90:74-80. [PMID: 30701950 DOI: 10.26442/terarkh201890874-80] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Ascites and hydrothorax may be the symptoms of congestive heart failure and do not always reflects presense of the decompensated liver cirrhosis. Clinical examination of patient with chronic hepatitis C which cyanosis of the lips, cervival veins pulsation, a triple heart rhythm indicated on pathology of the heart (constrictive pericarditis), which was confirmed by instrumental methods. Congestive heart failure has lead to the congestive liver in a young female patient. Regression of all the symptoms of heart failure occurred after surgical treatment (pericardectomy).
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Affiliation(s)
- I N Tikhonov
- Scientific Research Department of Innovative Therapy of the Scientific and Technological Park of Biomedicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia.,V.H. Vasilenko Clinic of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
| | - M S Zharkova
- V.H. Vasilenko Clinic of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
| | - M V Maevskaya
- The Department of Propaedeutics of Internal Medicine of the Faculty of Physiology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
| | - V N Zozulya
- The Department of Propaedeutics of Internal Medicine of the Faculty of Physiology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
| | - T P Nekrasova
- Acad. A.I. Strukov Department of Pathological Anatomy, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
| | - M G Arslanyan
- V.H. Vasilenko Clinic of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
| | - N P Musina
- V.H. Vasilenko Clinic of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
| | - M A Tatarkina
- V.H. Vasilenko Clinic of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
| | - R T Rzaev
- V.H. Vasilenko Clinic of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
| | - K B Puzakov
- V.H. Vasilenko Clinic of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
| | - V T Ivashkin
- Scientific Research Department of Innovative Therapy of the Scientific and Technological Park of Biomedicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia.,V.H. Vasilenko Clinic of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia.,The Department of Propaedeutics of Internal Medicine of the Faculty of Physiology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
| | - M S Malikova
- B.V. Petrovsky Russian Scientific Center of Surgery, Moscow, Russia
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48
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Abstract
Acute liver failure (ALF) is a rare but highly fatal condition. The most common causes include drug-induced and viral hepatitis, but other less common etiologies, especially autoimmune hepatitis, Budd-Chiari syndrome, and Wilson disease, need to be considered. Because diagnosis is frequently tied to potential for reversibility of ALF and prognosis, early identification in a timely manner is crucial. Other causes of ALF are more easily recognizable based on specific circumstances, such as ALF in pregnancy or ischemic hepatitis. Ultimately, maintaining a wide differential diagnosis in patients with ALF is essential to identifying the proper treatment and prognosis.
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Affiliation(s)
- Russell Rosenblatt
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, 1305 York Avenue, 4th Floor, New York, NY 10021, USA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, 1305 York Avenue, 4th Floor, New York, NY 10021, USA.
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49
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Arcos-Machancoses JV, Molera Busoms C, Julio Tatis E, Victoria Bovo M, Quintero Bernabeu J, Juampérez Goñi J, Crujeiras Martínez V, Martin de Carpi J. Accuracy of the 2008 Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Children. Pediatr Gastroenterol Hepatol Nutr 2018; 21:118-126. [PMID: 29713609 PMCID: PMC5915689 DOI: 10.5223/pghn.2018.21.2.118] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/28/2017] [Accepted: 12/18/2017] [Indexed: 02/07/2023] Open
Abstract
PURPOSE Classical criteria for diagnosis of autoimmune hepatitis (AIH) are intended as research tool and are difficult to apply at patient's bedside. We aimed to study the accuracy of simplified criteria and the concordance with the expert diagnosis based on the original criteria. METHODS A cohort of children under study for liver disorder was selected through consecutive sampling to obtain the prevalence of AIH within the group of differential diagnoses. AIH was defined, based on classical criteria, through committee review of medical reports. Validity indicators of the simplified criteria were obtained in an intention to diagnose approach. Optimal cut-off and the area under the receiver operating characteristic (ROC) curve were calculated. RESULTS Out of 212 cases reviewed, 47.2% were AIH. For the optimal cut-off (6 points), the simplified criteria showed a sensitivity of 72.0% and a specificity of 96.4%, with a 94.7% positive and a 79.4% negative predictive value. The area under the ROC curve was 94.3%. There was a good agreement in the pre-treatment concordance between the classical and the simplified criteria (kappa index, 0.775). CONCLUSION Simplified criteria provide a moderate sensitivity for the diagnosis of AIH, but may help in indicating treatment in cases under suspicion with 6 or more points.
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Affiliation(s)
| | - Cristina Molera Busoms
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
| | - Ecaterina Julio Tatis
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain
| | - María Victoria Bovo
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain
| | - Jesús Quintero Bernabeu
- Department of Pediatric Gastroenterology and Hepatology, Vall d'Hebron Hospital (VHH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
| | - Javier Juampérez Goñi
- Department of Pediatric Gastroenterology and Hepatology, Vall d'Hebron Hospital (VHH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
| | - Vanessa Crujeiras Martínez
- Department of Pediatric Gastroenterology and Hepatology, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, Spain
| | - Javier Martin de Carpi
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
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50
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Wang QX, Yan L, Ma X. Autoimmune Hepatitis in the Asia-Pacific Area. J Clin Transl Hepatol 2018; 6:48-56. [PMID: 29577032 PMCID: PMC5862999 DOI: 10.14218/jcth.2017.00032] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 09/23/2017] [Accepted: 10/26/2017] [Indexed: 02/06/2023] Open
Abstract
Autoimmune hepatitis has been considered as a relatively rare immunological liver disease, especially in the Asia-Pacific area. Although the diagnosis criteria and immunosuppressive treatment regimens have been established, there are still some challenges. According to the different presentations, the personalized management of patients who suffer from this disease, including those with chronic or acute severe onset, the autoantibody-negative phenotype and cirrhosis are necessarily descriptive. Each subgroup of patients should receive an individualized therapy. Here, we review the recent studies of autoimmune hepatitis, mainly focusing on the epidemiology and genetics, personalized diagnostics, individualized treatment strategies, special subgroups and outcomes. Most of the research in the literature is based on Japanese and Chinese populations.
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Affiliation(s)
- Qi-Xia Wang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Li Yan
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xiong Ma
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
- *Correspondence to: Xiong Ma, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China. Tel: +86-21-63200874, Fax: +86-21-63266027, E-mail:
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