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Chen Y, Chen R, Li H, Shuai Z. Clinical management of autoimmune liver diseases: juncture, opportunities, and challenges ahead. Immunol Res 2025; 73:67. [PMID: 40195209 PMCID: PMC11976385 DOI: 10.1007/s12026-025-09622-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 03/14/2025] [Indexed: 04/09/2025]
Abstract
The three major autoimmune liver diseases are autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC).These conditions are assumed to result from a breakdown in immunological tolerance, which leads to an inflammatory process that causes liver damage.The self-attack is started by T-helper cell-mediated identification of liver autoantigens and B-cell production of autoantibodies,and it is maintained by a reduction in the number and activity of regulatory T-cells.Infections and environmental factors have been explored as triggering factors for these conditions, in addition to a genetic predisposition.Allelic mutations in the HLA locus have been linked to vulnerability, as have relationships with single nucleotide polymorphisms in non-HLA genes.Despite the advances in the management of these diseases, there is no curative treatment for these disorders, and a significant number of patients eventually progress to an end-stage liver disease requiring liver transplantation.In this line, tailored immune-therapeutics have emerged as possible treatments to control the disease.In addition, early diagnosis and treatment are pivotal for reducing the long-lasting effects of these conditions and their burden on quality of life.Herein we present a review of the etiology, clinical presentation, diagnosis, and challenges on ALDs and the feasible solutions for these complex diseases.
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MESH Headings
- Humans
- Hepatitis, Autoimmune/therapy
- Hepatitis, Autoimmune/diagnosis
- Hepatitis, Autoimmune/immunology
- Hepatitis, Autoimmune/etiology
- Cholangitis, Sclerosing/therapy
- Cholangitis, Sclerosing/diagnosis
- Cholangitis, Sclerosing/immunology
- Liver Cirrhosis, Biliary/therapy
- Liver Cirrhosis, Biliary/diagnosis
- Liver Cirrhosis, Biliary/immunology
- Animals
- Immunotherapy/methods
- Autoimmune Diseases/therapy
- Autoimmune Diseases/diagnosis
- Disease Management
- Genetic Predisposition to Disease
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Affiliation(s)
- Yangfan Chen
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Ruofei Chen
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Haiyan Li
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Zongwen Shuai
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, 230032, China.
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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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Schaapman J, Shumbayawonda E, Castelo-Branco M, Caseiro Alves F, Costa T, Fitzpatrick E, Tupper K, Dhawan A, Deheragoda M, Sticova E, French M, Beyer C, Rymell S, Tonev D, Verspaget H, Neubauer S, Banerjee R, Lamb H, Coenraad M. MRI-serum-based score accurately identifies patients undergoing liver transplant without rejection avoiding the need for liver biopsy: A multisite European study. Liver Transpl 2025; 31:355-368. [PMID: 39171987 PMCID: PMC11827683 DOI: 10.1097/lvt.0000000000000450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 07/09/2024] [Indexed: 08/23/2024]
Abstract
Serum liver tests (serum tests) and histological assessment for T-cell-mediated rejection are essential for post-liver transplant monitoring. Liver biopsy carries a risk of complications that are preferably avoided in low-risk patients. Multiparametric magnetic resonance imaging (mpMRI) is a reliable noninvasive diagnostic method that quantifies liver disease activity and has prognostic utility. Our aim was to determine whether using mpMRI in combination with serum tests could noninvasively identify low-risk patients who underwent liver transplants who are eligible to avoid invasive liver biopsies. In a multicenter prospective study (RADIcAL2), including 131 adult and pediatric (children and adolescent) patients with previous liver transplants from the Netherlands, Portugal, and the United Kingdom, concomitant mpMRI and liver biopsies were performed. Biopsies were centrally read by 2 expert pathologists. T-cell-mediated rejection was assessed using the BANFF global assessment. Diagnostic accuracy to discriminate no rejection versus indeterminate or T-cell-mediated liver transplant rejection was performed using the area under the receiver operating characteristic curve. In this study, 52% of patients received a routine (protocol) biopsy, while 48% had a biopsy for suspicion of pathology. Thirty-eight percent of patients had no rejection, while 62% had either indeterminate (21%) or T-cell-mediated rejection (41%). However, there was a high interobserver variability (0 < Cohen's Kappa < 0.85) across all histology scores. The combined score of mpMRI and serum tests had area under the receiver operating characteristic curve 0.7 (negative predictive value 0.8) to identify those without either indeterminate or T-cell-mediated rejection. Combining both imaging and serum biomarkers into a composite biomarker (imaging and serum biomarkers) has the potential to monitor the liver graft to effectively risk stratify patients and identify those most likely to benefit from a noninvasive diagnostic approach, reducing the need for liver biopsy.
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Affiliation(s)
- Jelte Schaapman
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Miguel Castelo-Branco
- CIBIT (Coimbra Institute for Biomedical Imaging and Translational Research), Faculdade de Medicina, Instituto de Ciências Nucleares Aplicadas à Saúde, Universidade de Coimbra, Coimbra, Portugal
| | - Filipe Caseiro Alves
- CIBIT (Coimbra Institute for Biomedical Imaging and Translational Research), Faculdade de Medicina, Instituto de Ciências Nucleares Aplicadas à Saúde, Universidade de Coimbra, Coimbra, Portugal
| | - Tania Costa
- CIBIT (Coimbra Institute for Biomedical Imaging and Translational Research), Faculdade de Medicina, Instituto de Ciências Nucleares Aplicadas à Saúde, Universidade de Coimbra, Coimbra, Portugal
| | | | - Katie Tupper
- Institute of Liver Studies, Kings College London, London, UK
| | - Anil Dhawan
- Institute of Liver Studies, Kings College London, London, UK
| | | | - Eva Sticova
- Institute of Liver Studies, Kings College London, London, UK
| | | | - Cayden Beyer
- Translational Science, Perspectum Ltd., Oxford UK
| | | | | | - Hein Verspaget
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Stefan Neubauer
- Radcliffe Department of Medicine, Oxford NIHR Biomedical Research Centre, Oxford, UK
| | | | - Hildo Lamb
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Minneke Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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Xing Y, Wang W, Wan N, Zhang D, Shan M, Wang G. The influence of vaginal microbiota on the pregnancy outcome of artificial insemination with husband's sperm based on microscope images combined with PCR fluorescence method. SLAS Technol 2025; 30:100242. [PMID: 39725275 DOI: 10.1016/j.slast.2024.100242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 11/11/2024] [Accepted: 12/22/2024] [Indexed: 12/28/2024]
Abstract
The vaginal microbiota plays an important role in reproductive health, especially in the process of artificial insemination. The imbalance of microbiota may affect pregnancy outcomes. Therefore, this study aims to explore the composition of vaginal microbiota and its impact on artificial insemination pregnancy outcomes, combined with microscopic images and PCR fluorescence methods, in order to provide scientific basis for improving the pregnancy outcomes of husband sperm artificial insemination. This study included female patients who underwent artificial insemination with husband's sperm and collected reproductive tract samples. By observing the microbial community morphology in the sample under a microscope and analyzing microbial DNA using PCR fluorescence method, the microbial ecological status is evaluated. Among women with successful pregnancy, the proportion of beneficial bacteria (such as lactic acid bacteria) is higher, while the abundance of pathogenic bacteria is significantly reduced. Specific microbial markers detected by PCR fluorescence method are positively correlated with pregnancy rate. Therefore, the microecological state of the female reproductive tract has a significant impact on the pregnancy outcome of artificial insemination. Maintaining a good microecological balance, especially increasing the proportion of beneficial bacteria, can help improve the success rate of artificial insemination.
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Affiliation(s)
- Yanling Xing
- Department of Gynecology, Heilongjiang Provincial Hospital, Harbin, 150000, Heilongjiang Province, China
| | - Wei Wang
- Department of Reproductive medicine, Heilongjiang Provincial Hospital, Harbin, 150000, Heilongjiang Province, China
| | - Na Wan
- Department of Gynecology, Heilongjiang Provincial Hospital, Harbin, 150000, Heilongjiang Province, China
| | - Dongmei Zhang
- Department of Reproductive medicine, Heilongjiang Provincial Hospital, Harbin, 150000, Heilongjiang Province, China
| | - Mei Shan
- Department of Reproductive medicine, Heilongjiang Provincial Hospital, Harbin, 150000, Heilongjiang Province, China
| | - Guan Wang
- Department of Reproductive medicine, Heilongjiang Provincial Hospital, Harbin, 150000, Heilongjiang Province, China.
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Zhao JT, Niu QH, Li JJ, Zong SK, Liu H, Zhang LX. Autoimmune hepatitis presenting with recurrent fever and HBsAg positivity: A case report and review of the literature. Shijie Huaren Xiaohua Zazhi 2025; 33:75-80. [DOI: 10.11569/wcjd.v33.i1.75] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/11/2024] [Accepted: 12/17/2024] [Indexed: 01/25/2025] Open
Abstract
BACKGROUND The clinical manifestations of autoimmune hepatitis (AIH) lack specificity, with fever being uncommon. This paper presents a case of AIH characterized by recurrent fever and HBsAg positivity, ultimately diagnosed through liver biopsy, highlighting the importance of pathological evaluation in accurately diagnosing AIH.
CASE SUMMARY A patient was admitted to the hospital due to "recurrent fever lasting for two years", with an unknown etiology despite multiple visits over this period. In our hospital, a final diagnosis of AIH was achieved through further testing of autoantibodies and a liver biopsy. Following treatment with corticosteroids combined with immunosuppressants and prophylactic therapy against hepatitis B virus, the patient's condition stabilized, and no recurrence has been observed.
CONCLUSION AIH is often challenging to diagnose, and the presence of confounding factors can further complicate the diagnostic process, leading to a higher likelihood of missed diagnoses. Positive autoantibodies may be detected in patients with hepatitis B, and there are notable individual variations in antibody titers. Consequently, this variability adds complexity to the diagnosis, which clinicians should be particularly mindful of. For both patients with and without AIH, timely liver histology assessment is essential for confirming the diagnosis. The early initiation of immunosuppressive therapy holds significant importance in delaying disease progression and improving patient prognosis.
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Affiliation(s)
- Jun-Tong Zhao
- Department of Hepatology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
| | - Qing-Hui Niu
- Department of Hepatology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
| | - Jin-Jin Li
- Department of Hepatology, The Sixth People's Hospital of Qingdao, Qingdao 266000, Shandong Province, China
| | - Shou-Kai Zong
- Department of Breast and Thyroid Surgery, Rizhao People's Hospital, Rizhao 276800, Shandong Province, China
| | - Huan Liu
- Department of Liver Disease, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
| | - Long-Xiao Zhang
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
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Zhao JT, Niu QH, Li JJ, Zong SK, Liu H, Zhang LX. Autoimmune hepatitis presenting with recurrent fever and HBsAg positivity: A case report and review of the literature. Shijie Huaren Xiaohua Zazhi 2025; 33:73-78. [DOI: 10.11569/wcjd.v33.i1.73] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/11/2024] [Accepted: 12/17/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND The clinical manifestations of autoimmune hepatitis (AIH) lack specificity, with fever being uncommon. This paper presents a case of AIH characterized by recurrent fever and HBsAg positivity, ultimately diagnosed through liver biopsy, highlighting the importance of pathological evaluation in accurately diagnosing AIH.
CASE SUMMARY A patient was admitted to the hospital due to "recurrent fever lasting for two years", with an unknown etiology despite multiple visits over this period. In our hospital, a final diagnosis of AIH was achieved through further testing of autoantibodies and a liver biopsy. Following treatment with corticosteroids combined with immunosuppressants and prophylactic therapy against hepatitis B virus, the patient's condition stabilized, and no recurrence has been observed.
CONCLUSION AIH is often challenging to diagnose, and the presence of confounding factors can further complicate the diagnostic process, leading to a higher likelihood of missed diagnoses. Positive autoantibodies may be detected in patients with hepatitis B, and there are notable individual variations in antibody titers. Consequently, this variability adds complexity to the diagnosis, which clinicians should be particularly mindful of. For both patients with and without AIH, timely liver histology assessment is essential for confirming the diagnosis. The early initiation of immunosuppressive therapy holds significant importance in delaying disease progression and improving patient prognosis.
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Affiliation(s)
- Jun-Tong Zhao
- Department of Hepatology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
| | - Qing-Hui Niu
- Department of Hepatology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
| | - Jin-Jin Li
- Department of Hepatology, The Sixth People's Hospital of Qingdao, Qingdao 266000, Shandong Province, China
| | - Shou-Kai Zong
- Department of Breast and Thyroid Surgery, Rizhao People's Hospital, Rizhao 276800, Shandong Province, China
| | - Huan Liu
- Department of Liver Disease, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
| | - Long-Xiao Zhang
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
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Duan X, Chai W, Wang Y, Zhao L. A case report of autoimmune hepatitis with delayed diagnosis in a general practice clinic. Asian J Surg 2024; 47:3765-3766. [PMID: 38714406 DOI: 10.1016/j.asjsur.2024.04.117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 04/18/2024] [Indexed: 05/09/2024] Open
Affiliation(s)
- Xiaokai Duan
- Department of General Practice, Zhengzhou First People's Hospital, Zhengzhou, China.
| | - Weifang Chai
- Department of General Practice, Zhengzhou First People's Hospital, Zhengzhou, China
| | - Yunling Wang
- Department of Ultrasound Diagnosis, Zhengzhou First People's Hospital, Zhengzhou, China
| | - Limin Zhao
- Pathology Department, Zhengzhou First People's Hospital, Zhengzhou, China
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Chen H, Ren W, Yang X, Hu P, Wang S, Xu C, Lv F, Zhao Y, Yin Q, Zheng W, Xu J, Pan H. Development and validation of a noninvasive prediction model for significant hepatic liver fibrosis in Chinese patients with autoimmune hepatitis. Ann Hepatol 2024; 29:101287. [PMID: 38266674 DOI: 10.1016/j.aohep.2024.101287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 12/10/2023] [Accepted: 01/14/2024] [Indexed: 01/26/2024]
Abstract
INTRODUCTION AND OBJECTIVES Autoimmune hepatitis (AIH) is a prevalent noninfectious liver disease. However, there is currently a lack of noninvasive tests appropriate for evaluating liver fibrosis in AIH patients. The objective of this study was to develop and validate a predictive model for noninvasive assessment of significant liver fibrosis (S ≥ 2) in patients to provide a reliable method for evaluating liver fibrosis in individuals with AIH. MATERIALS AND METHODS The clinical data of 374 AIH patients were analyzed. A prediction model was established through logistic regression in the training set, and bootstrap method was used to validate the models internally. In addition, the clinical data of 109 AIH patients were collected for external verification of the model.The model was expressed as a nomogram, and area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model. RESULTS Logistic regression analysis revealed that age, platelet count (PLT), and the A/G ratio were identified as independent risk factors for liver fibrosis in AIH patients (P < 0.05). The diagnostic model that was composed of age, PLT and A/G was superior to APRI and FIB-4 in both the internal validation (0.872, 95%CI: 0.819-0.924) and external validation (0.829, 95%CI: 0.753-0.904). CONCLUSIONS Our predictive model can predict significant liver fibrosis in AIH patients more accurately, simply, and noninvasively.
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Affiliation(s)
- Hanzhu Chen
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China; Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, PR China
| | - Wenya Ren
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China; Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, PR China
| | - Xingdi Yang
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, PR China
| | - Piao Hu
- The First People's Hospital of Xiaoshan District, Xiaoshan First Affiliated Hospital of Wenzhou Medical University, Hangzhou 311200 Zhejiang, PR China
| | - Shouhao Wang
- Hepatology Diagnosis and Treatment Center, The First Affiliated Hospital of Wenzhou Medical University & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Wenzhou, Zhejiang 325035, PR China
| | - Chengan Xu
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, PR China
| | - Fei Lv
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, PR China
| | - Yue Zhao
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, PR China
| | - Qiaoqiao Yin
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, PR China
| | - Wei Zheng
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, PR China
| | - Jing Xu
- Hepatology Department II, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310023, PR China.
| | - Hongying Pan
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, PR China.
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Wang L, Hu YF, Yang AY, Du ZX, Liu HL, Zhu P, Li LQ, Zhong YD, Xu ZY, Wang SS, Yang YF. Development and validation of a noninvasive prediction model of autoimmune hepatitis in patients with liver diseases. Scand J Gastroenterol 2024; 59:62-69. [PMID: 37649307 DOI: 10.1080/00365521.2023.2249571] [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: 07/25/2023] [Revised: 08/08/2023] [Accepted: 08/14/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND AND AIMS There is no golden standard for the diagnosis of autoimmune hepatitis which still dependent on liver biopsy currently. So, we developed a noninvasive prediction model to help optimize the diagnosis of autoimmune hepatitis. METHODS From January 2017 to December 2019, 1739 patients who had undergone liver biopsy were seen in the second hospital of Nanjing, of which 128 were here for consultation. Clinical, laboratory, and histologic data were obtained retrospectively. Multivariable logistic regression analysis was employed to create a nomogram model that predicting the risk of autoimmune hepatitis. Internal and external validation was both performed to evaluate the model. RESULTS A total of 1288 patients with liver biopsy were enrolled (1184 from the second hospital of Nanjing, the remaining 104 from other centers). After the univariate and multivariate logistic regression analysis, nine variables including ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender were selected to establish the noninvasive prediction model. The nomogram model exhibits good prediction in diagnosing autoimmune hepatitis with AUROC of 0.967 (95% CI: 0.776-0.891) in internal validation and 0.835 (95% CI: 0.752-0.919) in external validation. CONCLUSIONS ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender are predictive factors for the diagnosis of autoimmune hepatitis in patients with unexplained liver diseases. The predictive nomogram model built by the nine predictors achieved good prediction for diagnosing autoimmune hepatitis.
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Affiliation(s)
- Li Wang
- Nanjing University of Chinese Medicine, Nanjing, China
- The Second Hospital of Nanjing, Teaching Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yi-Fan Hu
- Nanjing University of Chinese Medicine, Nanjing, China
| | - An-Yin Yang
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhi-Xiang Du
- Nanjing University of Chinese Medicine, Nanjing, China
| | | | - Ping Zhu
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Li-Qiu Li
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Yan-Dan Zhong
- The Second Hospital of Nanjing, Teaching Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | | | | | - Yong-Feng Yang
- Nanjing University of Chinese Medicine, Nanjing, China
- The Second Hospital of Nanjing, Teaching Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Nastasio S, Mosca A, Alterio T, Sciveres M, Maggiore G. Juvenile Autoimmune Hepatitis: Recent Advances in Diagnosis, Management and Long-Term Outcome. Diagnostics (Basel) 2023; 13:2753. [PMID: 37685291 PMCID: PMC10486972 DOI: 10.3390/diagnostics13172753] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/11/2023] [Accepted: 08/13/2023] [Indexed: 09/10/2023] Open
Abstract
Juvenile autoimmune hepatitis (JAIH) is severe immune-mediated necro-inflammatory disease of the liver with spontaneous progression to cirrhosis and liver failure if left untreated. The diagnosis is based on the combination of clinical, laboratory and histological findings. Prothrombin ratio is a useful prognostic factor to identify patients who will most likely require a liver transplant by adolescence or early adulthood. JAIH treatment consists of immune suppression and should be started promptly at diagnosis to halt inflammatory liver damage and ultimately prevent fibrosis and progression to end-stage liver disease. The risk of relapse is high especially in the setting of poor treatment compliance. Recent evidence however suggests that treatment discontinuation is possible after a prolonged period of normal aminotransferase activity without the need for liver biopsy prior to withdrawal.
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Affiliation(s)
- Silvia Nastasio
- Division of Gastroenterology, Hepatology & Nutrition, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA;
| | - Antonella Mosca
- Hepatogastroenterology, Rehabilitative Nutrition, Digestive Endoscopy and Liver Transplant Unit, ERN RARE LIVER, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.M.); (T.A.)
| | - Tommaso Alterio
- Hepatogastroenterology, Rehabilitative Nutrition, Digestive Endoscopy and Liver Transplant Unit, ERN RARE LIVER, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.M.); (T.A.)
| | - Marco Sciveres
- Pediatric Department and Transplantation, ISMETT, 90133 Palermo, Italy;
| | - Giuseppe Maggiore
- Hepatogastroenterology, Rehabilitative Nutrition, Digestive Endoscopy and Liver Transplant Unit, ERN RARE LIVER, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.M.); (T.A.)
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Sacoto DH, Turbay V, Sandhu J, Chaudhari S, Cosico J. The Threat of Weight-Loss Over the Counter Supplements: A Case of Camellia Sinensis Autoimmune Hepatitis. Cureus 2023; 15:e36023. [PMID: 37050988 PMCID: PMC10085537 DOI: 10.7759/cureus.36023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/11/2023] [Indexed: 04/14/2023] Open
Abstract
Autoimmune hepatitis (AIH) arises as a result of environmental and immunological interactions. Herbal and dietary supplements (HDS) are known triggers, and approximately half of the U.S. adult population consumes them, even though they are restricted. Therefore, the importance of recognizing potential triggers of AIH is considered relevant. The mechanism behind HDS Camellia Sinensis inducing AIH is related to its compounds, catechins, which induce reactive oxygen species leading to a liver immune-mediated response. We present here a challenging case of a middle-aged woman with AIH following the consumption of a weight-loss Mexican green tea containing Camellia Sinensis.
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Affiliation(s)
- Daniel Hernan Sacoto
- Department of Internal Medicine, Metropolitan Medical Center/New York Medical College, New York, USA
| | - Valentina Turbay
- Department of Internal Medicine, Advocate Christ Medical Center, Chicago, USA
| | - Jagbir Sandhu
- Department of Pathology, Metropolitan Medical Center/New York Medical College, New York, USA
| | - Shobhana Chaudhari
- Department of Internal Medicine, Metropolitan Medical Center/New York Medical College, New York, USA
| | - Juan Cosico
- Department of Internal Medicine, Metropolitan Medical Center/New York Medical College, New York, USA
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12
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Bajre M, Moawad M, Shumbayawonda E, Carolan JE, Hart J, Culver E, Heneghan M. LiverMultiScan as an alternative to liver biopsy to monitor autoimmune hepatitis in the National Health Service in England: an economic evaluation. BMJ Open 2022; 12:e058999. [PMID: 36691214 PMCID: PMC9462097 DOI: 10.1136/bmjopen-2021-058999] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 08/21/2022] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a rare chronic progressive liver disease, managed with corticosteroids and immunosuppressants and monitored using a combination of liver biochemistry and histology. Liver biopsy (gold standard) is invasive, costly and has risk of complications. Non-invasive imaging using multiparametric magnetic resonance (mpMR) can detect the presence and extent of hepatic fibroinflammation in a risk-free manner. OBJECTIVE To conduct early economic modelling to assess the affordability of using mpMR as an alternative to liver biopsy. METHODS Medical test costs associated with following 100 patients over a 5-year time horizon were assessed from a National Health Service payor perspective using tariff costs and average biopsy-related adverse events costs. Sensitivity analyses modelling the cost consequences of increasing the frequency of mpMR monitoring within the fixed cost of liver biopsy were performed. RESULTS Per 100 moderate/severe AIH patients receiving an annual mpMR scan (in place of biopsy), early economic modelling showed minimum cost savings of £232 333. Per 100 mild/moderate AIH patients receiving three mpMR scans over 5 years estimated minimum cost savings were £139 400. One-way sensitivity analyses showed increasing the frequency of mpMR scans from 5 to 10 over 5 years in moderate/severe AIH patients results in a cost saving of £121 926.20. In patients with mild/moderate AIH, an increase from 3 to 6 mpMR scans over 5 years could save £73 155.72. In a minimalistic approach, the use of 5 mpMR scans was still cost saving (£5770.48) if they were to replace two biopsies over the 5-year period for all patients with moderate/severe or mild/moderate AIH. CONCLUSIONS Integration of mpMR scans in AIH patient pathways leads to significant cost savings when liver biopsy frequency is either reduced or eliminated, in addition to improved patient experience and clinician acceptability as well as providing detailed phenotyping to improve patient outcomes. TRIAL REGISTRATION NCT03979053.
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Affiliation(s)
- Mamta Bajre
- Oxford Academic Health Science Network, Oxford, UK
| | - Mina Moawad
- Oxford Academic Health Science Network, Oxford, UK
| | | | | | - Julie Hart
- Oxford Academic Health Science Network, Oxford, UK
| | - Emma Culver
- John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
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13
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Autoimmune Hepatitis—Challenging Diagnosis. Medicina (B Aires) 2022; 58:medicina58070896. [PMID: 35888614 PMCID: PMC9318073 DOI: 10.3390/medicina58070896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 06/23/2022] [Accepted: 06/30/2022] [Indexed: 12/04/2022] Open
Abstract
The incidence of Autoimmune Hepatitis (AIH) increases worldwide. If undiagnosed, it may progress end-stage liver disease. Unfortunately, there is no characteristic clinical presentation of this disease, which makes the illness hard to recognize. A case report illustrates the difficulties of diagnosing the patient during his two hospitalizations and his final treatment with prednisolone which improved the patient’s condition.
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14
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Tan CK, Ho D, Wang LM, Kumar R. Drug-induced autoimmune hepatitis: A minireview. World J Gastroenterol 2022; 28:2654-2666. [PMID: 35979160 PMCID: PMC9260871 DOI: 10.3748/wjg.v28.i24.2654] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/15/2021] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
Drug-induced autoimmune hepatitis (DIAIH) is a specific phenotype of drug-induced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation. Drugs implicated in DIAIH include antimicrobials such as nitrofurantoin and minocycline, non-steroidal anti-inflammatory drugs, statins as well as anti-tumor necrosis agents. The clinical features of drug-induced liver injury are indistinguishable from idiopathic autoimmune hepatitis (AIH) as both may have positive AIH-related autoantibodies, elevated immunoglobulin G, as well as similar histopathological findings. In patients who show no clinical improvement, or there is progressive liver injury despite cessation of the suspected drug, a liver biopsy should be considered, whereby the presence of advance fibrosis on histology favors the diagnosis of idiopathic AIH. Empirical treatment with corticosteroids may be required in patients with non-resolving liver injury. A typical clinical scenario supportive of DIAIH includes a history of drug exposure with spontaneous resolution of liver injury after drug withdrawal and the absence of relapse after rapid steroid taper. In this article we report two cases of DIAIH secondary to Sorafenib and Atorvastatin along with a review of currently available literature. Early identification and treatment often lead to a favorable outcome in DIAIH.
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Affiliation(s)
- Chin Kimg Tan
- Gastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
- Medicine Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Singapore 529889, Singapore
| | - Danielle Ho
- Gastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
| | - Lai Mun Wang
- Section of Pathology, Department of Laboratory Medicine, Changi General Hospital, Singapore 529889, Singapore
- Pathology Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Singapore 529889, Singapore
| | - Rahul Kumar
- Gastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
- Medicine Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Singapore 529889, Singapore
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15
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Gordon V, Adhikary R, Appleby V, Das D, Day J, Delahooke T, Dixon S, Elphick D, Hardie C, Heneghan MA, Hoeroldt B, Hooper P, Hutchinson J, Jones R, Khan F, Aithal GP, Metcalf J, Nkhoma A, Pelitari S, Prince M, Prosser A, Sathyanarayana V, Saksena S, Vani D, Yeoman A, Abouda G, Nelson A, Gleeson D. Treatment and Outcome of Autoimmune Hepatitis (AIH): Audit of 28 UK centres. Liver Int 2022; 42:1571-1584. [PMID: 35286013 DOI: 10.1111/liv.15241] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 01/27/2022] [Accepted: 03/10/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND With few data regarding treatment and outcome of patients with AIH outside of large centres we present such a study of patients with AIH in 28 UK hospitals of varying size and facilities. METHODS Patients with AIH were identified in 14 University and 14 District General hospitals; incident cases during 2007-2015 and prevalent cases, presenting 2000-2015. Treatment and outcomes were analysed. RESULTS In 1267 patients with AIH, followed-up for 3.8(0-15) years, 5- and 10-year death/transplant rates were 7.1+0.8% and 10.1+1.3% (all-cause) and 4.0+0.6% and 5.9+1% (liver-related) respectively. Baseline parameters independently associated with death/transplantation for all-causes were: older age, vascular/respiratory co-morbidity, cirrhosis, decompensation, platelet count, attending transplant centre and for liver-related: the last four of these and peak bilirubin All-cause and liver-related death/transplantation was independently associated with: non-treatment with corticosteroids, non-treatment with a steroid-sparing agent (SSA), non-treatment of asymptomatic or non-cirrhotic patients and initial dose of Prednisolone >35mg/0.5mg/kg/day (all-cause only), but not with type of steroid (Prednisolone versus Budesonide) or steroid duration beyond 12-months. Subsequent all-cause and liver-death/transplant rates showed independent associations with smaller percentage fall in serum ALT after 1 and 3-months, but not with failure to normalise levels over 12-months. CONCLUSIONS We observed higher death/transplant rates in patients with AIH who were untreated with steroids (including asymptomatic or non-cirrhotic sub-groups), those receiving higher Prednisolone doses and those who did not receive an SSA. Similar death/transplant rates were seen in those receiving Prednisolone or Budesonide, those continuing steroids after 12-months and patients attaining normal ALT within 12-months versus not.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - 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
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16
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Fujita K, Oura K, Tadokoro T, Nakahara M, Tani J, Morishita A, Kobara H, Tsutsui K, Himoto T, Masaki T. Prognosis of probable autoimmune hepatitis patients: a single-center study in Japan. Intern Emerg Med 2021; 16:2155-2162. [PMID: 33783693 DOI: 10.1007/s11739-021-02720-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 03/18/2021] [Indexed: 10/21/2022]
Abstract
Autoimmune hepatitis (AIH) is an idiopathic inflammatory liver disease with genetic susceptibility and unknown environmental triggers. The gold standard for diagnosis, International Autoimmune Hepatitis Group (IAIHG) scoring system, classifies AIH as definite or probable. Conventional research on probable AIH has focused on the Caucasian population and there is little data pertaining to the Asian population. This study aimed to assess and compare the prognosis of Japanese patients with probable and definite AIH. In the current study, patients with probable and definite AIH diagnosed based on IAIHG scores between 1987 and 2018 were enrolled. As a result, 72 patients with definite AIH and 49 patients with probable AIH were evaluated. Univariate analysis revealed age, fibrosis stage 4, and the fibrosis-4 index were prognostic factors for overall survival. Multivariate analysis indicated that age and liver cirrhosis significantly affected the overall survival. When the cut off albumin-bilirubin score was set appropriately, cirrhosis was differentially diagnosed using albumin-bilirubin score with 100% sensitivity and 70.5% specificity. Classification of probable or definite disease did not alter overall survival with statistical significance. In conclusion, our findings suggest that probable AIH should be managed as definite AIH is managed in Japanese population. The albumin-bilirubin score helps identify liver cirrhosis and is a prognostic biomarker for overall survival.
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Affiliation(s)
- Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan.
| | - Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Mai Nakahara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Joji Tani
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Hideki Kobara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Kunihiko Tsutsui
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectural University of Health Sciences, 281-1 Hara, Mure, Takamatsu, Kagawa, 761-0123, Japan.
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
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17
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Trivedi PJ, Hirschfield GM. Recent advances in clinical practice: epidemiology of autoimmune liver diseases. Gut 2021; 70:1989-2003. [PMID: 34266966 DOI: 10.1136/gutjnl-2020-322362] [Citation(s) in RCA: 117] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 06/24/2021] [Indexed: 12/13/2022]
Abstract
Autoimmune liver diseases are chronic inflammatory hepatobiliary disorders that when classically defined encompass three distinctive clinical presentations; primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Meaningful changes in disease epidemiology are reported, with increasing incidence and prevalence of AIH and PSC in Europe, and rising prevalence of PBC across Europe, North America and the Asia-Pacific region. However, there appears to be very significant global variation with contemporary incidence rates of disease per 100 000 ranging from 0.84 to 2.75 for PBC, 0.1 to 4.39 for PSC and 0.4 to 2.39 for AIH. Prevalence corresponds, and per 100 000 estimates for PBC range from 1.91 to 40.2, for PSC between 0.78 and 31.7 and for AIH from 4.8 to 42.9. Population-based studies and multicentre observational cohort series provide improved understanding of the clinical course that patients experience, highlighting variations in presenting phenotypes geographically and temporally. Collectively, while autoimmune liver diseases are rare, the clinical burden is disproportionately high relative to population incidence and prevalence. Age, sex and race also impact clinical outcomes, and patient morbidity and mortality are reflected by high need for gastroenterology, hepatology and organ transplant services.
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Affiliation(s)
- Palak J Trivedi
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre, University of Birmingham College of Medical and Dental Sciences, Birmingham, Birmingham, UK
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, UK
| | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Ontario, Canada
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18
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Arndtz K, Shumbayawonda E, Hodson J, Eddowes PJ, Dennis A, Thomaides-Brears H, Mouchti S, Kelly MD, Banerjee R, Neubauer S, Hirschfield GM. Multiparametric Magnetic Resonance Imaging, Autoimmune Hepatitis, and Prediction of Disease Activity. Hepatol Commun 2021; 5:1009-1020. [PMID: 34141986 PMCID: PMC8183180 DOI: 10.1002/hep4.1687] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 01/05/2021] [Accepted: 01/18/2021] [Indexed: 02/06/2023] Open
Abstract
Noninvasive monitoring of disease activity in autoimmune hepatitis (AIH) has potential advantages for patients for whom liver biopsy is invasive and with risk. We sought to understand the association of multiparametric magnetic resonance imaging (mpMRI) with clinical course of patients with AIH. We prospectively recruited 62 patients (median age, 55 years; 82% women) with clinically confirmed AIH. At recruitment, patients underwent mpMRI with LiverMultiScan alongside clinical investigations, which were repeated after 12-18 months. Associations between iron-corrected T1 (cT1) and other markers of disease were investigated at baseline and at follow-up. Discriminative performance of cT1, liver stiffness, and enhanced liver fibrosis (ELF) to identify those who failed to maintain remission over follow-up was investigated using the areas under the receiver operating characteristic curves (AUCs). Baseline cT1 correlated with alanine aminotransferase (Spearman's correlation coefficient [r S] = 0.28, P = 0.028), aspartate aminotransferase (r S = 0.26, P = 0.038), international normalized ratio (r S = 0.35 P = 0.005), Model for End-Stage Liver Disease (r S = 0.32, P = 0.020), ELF (r S = 0.29, P = 0.022), and liver stiffness r S = 0.51, P < 0.001). After excluding those not in remission at baseline (n = 12), 32% of the remainder failed to maintain remission during follow-up. Failure to maintain remission was associated with significant increases in cT1 over follow-up (AUC, 0.71; 95% confidence interval [CI], 0.52-0.90; P = 0.035) but not with changes in liver stiffness (AUC, 0.68; 95% CI, 0.49-0.87; P = 0.067) or ELF (AUC, 0.57; 95% CI, 0.37-0.78; P = 0.502). cT1 measured at baseline was a significant predictor of future loss of biochemical remission (AUC, 0.68; 95% CI, 0.53-0.83; P = 0.042); neither liver stiffness (AUC, 0.53; 95% CI, 0.34-0.71; P = 0.749) nor ELF (AUC, 0.52; 95% CI, 0.33-0.70; P = 0.843) were significant predictors of loss of biochemical remission. Conclusion: Noninvasive mpMRI has potential to contribute to risk stratification in patients with AIH.
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Affiliation(s)
- Katherine Arndtz
- Centre for Liver and Gastrointestinal ResearchNational Institute for Health Research (NIHR) Birmingham Liver Biomedical Research CentreBirminghamUnited Kingdom.,University Hospitals Birmingham National Health Service (NHS) Foundation TrustBirminghamUnited Kingdom
| | | | - James Hodson
- University Hospitals Birmingham National Health Service (NHS) Foundation TrustBirminghamUnited Kingdom
| | - Peter J Eddowes
- Centre for Liver and Gastrointestinal ResearchNational Institute for Health Research (NIHR) Birmingham Liver Biomedical Research CentreBirminghamUnited Kingdom.,NIHR Nottingham Biomedical Research CentreNottingham University Hospitals NHS Trust and University of NottinghamNottinghamUnited Kingdom
| | | | | | | | | | | | | | - Gideon M Hirschfield
- Centre for Liver and Gastrointestinal ResearchNational Institute for Health Research (NIHR) Birmingham Liver Biomedical Research CentreBirminghamUnited Kingdom.,Toronto Centre for Liver DiseaseUniversity Health NetworkTorontoONCanada
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19
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Gordon VM, Adhikary R, Aithal GP, Appleby V, Das D, Day J, Delahooke T, Dixon S, Elphick D, Hardie C, Heneghan M, Hoeroldt B, Hooper P, Hutchinson J, Jones RL, Khan F, Metcalf J, Nkhoma A, Pelitari S, Prince M, Prosser A, Saksena S, Sathyanarayana V, Vani D, Yeoman A, Gleeson D. Provision and standards of care for treatment and follow-up of patients with Autoimmune Hepatitis (AIH). Frontline Gastroenterol 2021; 13:126-132. [PMID: 35295749 PMCID: PMC8862490 DOI: 10.1136/flgastro-2020-101661] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 03/16/2021] [Accepted: 03/18/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a substantial UK health burden, but there is variation in care, facilities and in opinion regarding management. We conducted an audit of service provision and care of patients with AIH in 28 UK hospitals. METHODS Centres provided information about staffing, infrastructure and patient management (measured against predefined guideline-based standards) via a web-based data collection tool. RESULTS Hospitals (14 university hospitals (UHs), 14 district general hospitals (DGHs)) had median (range) of 8 (3-23) gastroenterologists; including 3 (0-10) hepatologists. Eight hospitals (29%, all DGHs) had no hepatologist. In individual hospital departments, there were 50% (18-100) of all consultants managing AIH: in DGH's 92% (20-100) vs 46% (17-100) in UHs. Specialist nurses managed AIH in only 18%. Seventeen (61%) hospitals had a histopathologist with a liver interest, these were more likely to find rosettes than those without (172/795 vs 50/368; p<0.001).Of 999 steroid-treated patients with ≥12 months follow-up, 25% received steroids for <12 months. After 1 year of treatment, 82% of patients achieved normal serum alanine aminotransaminase (ALT); this was higher in UHs than DGHs. Three-monthly liver blood tests were inadequately recorded in 26%. Of potentially eligible patients with liver decompensation, transplantation was apparently not considered in 5% (n=7). The same standards were attained in different types of hospital. CONCLUSION Management of AIH in UK hospitals is often shared between most gastroenterologists. Blood test monitoring and treatment duration are not always in line with recommendations. Some eligible patients with decompensation are not discussed with transplant teams. Care might be improved by expanding specialist input and management by fewer designated consultants.
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Affiliation(s)
- Victoria Mary Gordon
- Hepatology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | | | - Guruprasad P Aithal
- Nottingham Digestive Disease Centre, NIHR Biomedical Research Unit, Nottingham University, Nottingham, UK
| | - Victoria Appleby
- Gastroenterology, Bradford Teaching Hospitals Foundation Trust, Bradford, UK
| | | | - James Day
- Addenbrooke's Hospital, Cambridge, UK
| | | | | | | | | | - Michael Heneghan
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | | | | | - John Hutchinson
- Hepatology, York Teaching Hospital NHS Foundation Trust, York, UK
| | - Rebecca L Jones
- Department of Hepatology, St James's University Hospital, Leeds, UK
| | | | | | - Alick Nkhoma
- Gastroenterology Department, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
| | - Stavroula Pelitari
- Hepatology, University Hospitals Coventry and Warwickshire NHS Trust Gastroenterology, Coventry, UK
| | | | | | | | | | - Deven Vani
- Mid Yorkshire Hospitals NHS Trust, Wakefield, UK
| | - Andrew Yeoman
- Gwent Liver Unit, Aneurin Bevan University Health Board, Newport, UK
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20
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Adiponectin is Increased in Pediatric Patients With Autoimmune Hepatitis Independent of Body Weight. J Pediatr Gastroenterol Nutr 2020; 71:e118-e123. [PMID: 32960544 DOI: 10.1097/mpg.0000000000002825] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVE A high prevalence of obesity is reported in children and adolescents with autoimmune hepatitis (AIH). Adipokines participate in inflammatory processes. The objective of this study was to examine the relationship between excess weight and systemic inflammation, adipokines, and ghrelin in adolescents with AIH. METHOD This case-controlled study included 27 adolescents with AIH (13 with excess weight and 14 with normal weight) and a control group. Excess weight was defined by a body mass index/age Z score >+1 standard deviation. Adipokines (adiponectin, leptin, tumor necrosis factor alpha, interleukin 6 [IL-6], and IL-10) and ghrelin were measured with Luminex technology. RESULTS Adiponectin (μg/mL) was higher (P < 0.001) in AIH adolescents with and without excess weight (median: 35.0 and 42.1, respectively) than in normal-weight (17.5) and excess-weight (17.0) controls. Leptin was higher (P < 0.001) in excess-weight AIH patients (18.0 ng/mL) and controls (19.8 ng/mL) than in normal-weight AIH (7.7 ng/mL) and control (7.0 ng/mL) adolescents. IL-6 levels were higher in excess-weight (3.8 pg/mL) and normal-weight (3.8 pg/mL) AIH patients than in excess-weight (1.1 pg/mL) and normal-weight (0.5 pg/mL) controls. IL-10 levels were higher (5.2 pg/mL) in normal-weight AIH patients than in excess-weight (1.8 pg/mL) and normal-weight (2.1 pg/mL) controls. Ferritin levels were lower in patients with AIH than in controls. CONCLUSIONS Independent of body weight, AIH patients had higher levels of adipokines, especially adiponectin and IL-6. Leptin levels were associated with body weight and were not influenced by AIH. IL-10 levels were associated with lean tissue in AIH.
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21
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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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22
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Chapman RW, Aspinall RJ, Trivedi P, Wright G, Heneghan M. Challenges in the use of corticosteroids in the management of autoimmune hepatitis. Br J Hosp Med (Lond) 2019; 80:594-599. [PMID: 31589514 DOI: 10.12968/hmed.2019.80.10.594] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Autoimmune hepatitis is widely assumed by health-care professionals to be a disease that is easily controlled through the use of corticosteroids and immunosuppressants but recent studies in the UK indicate highly variable treatment regimens and often unsatisfactory treatment outcomes, such as dependence on long-term high-dose steroids and ongoing need for liver transplantation in some cases. The therapeutic use of the systemically acting corticosteroid prednisolone results in unacceptable side effects in many patients. Recent evidence suggests that it is not always necessary to use high-dose steroids (>0.5 mg/kg/d) to attain remission; and side effects may also be minimised through more targeted therapy with the less systemically-absorbed corticosteroid, budesonide. The authors offer advice on the stratification of treatment for these patients and suggest changes to improve the services available for people with autoimmune hepatitis in the UK.
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Affiliation(s)
- Roger W Chapman
- Consultant Hepatologist, John Radcliffe Hospital, University of Oxford, Oxford
| | | | - Palak Trivedi
- Consultant Hepatologist and Clinician Scientist, NIHR Birmingham BRC, University of Birmingham, Birmingham
| | - Gavin Wright
- Consultant Hepatologist/Gastroenterologist, Basildon & Thurrock University Hospital, Basildon, Essex
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23
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Andrade RJ, Aithal GP, Björnsson ES, Kaplowitz N, Kullak-Ublick GA, Larrey D, Karlsen TH. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol 2019; 70:1222-1261. [PMID: 30926241 DOI: 10.1016/j.jhep.2019.02.014] [Citation(s) in RCA: 630] [Impact Index Per Article: 105.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 02/14/2019] [Indexed: 02/07/2023]
Abstract
Idiosyncratic (unpredictable) drug-induced liver injury is one of the most challenging liver disorders faced by hepatologists, because of the myriad of drugs used in clinical practice, available herbs and dietary supplements with hepatotoxic potential, the ability of the condition to present with a variety of clinical and pathological phenotypes and the current absence of specific biomarkers. This makes the diagnosis of drug-induced liver injury an uncertain process, requiring a high degree of awareness of the condition and the careful exclusion of alternative aetiologies of liver disease. Idiosyncratic hepatotoxicity can be severe, leading to a particularly serious variety of acute liver failure for which no effective therapy has yet been developed. These Clinical Practice Guidelines summarize the available evidence on risk factors, diagnosis, management and risk minimization strategies for drug-induced liver jury.
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Trivedi PJ, Hubscher SG, Heneghan M, Gleeson D, Hirschfield GM. Grand round: Autoimmune hepatitis. J Hepatol 2019; 70:773-784. [PMID: 30465775 DOI: 10.1016/j.jhep.2018.11.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Revised: 10/11/2018] [Accepted: 11/09/2018] [Indexed: 12/12/2022]
Abstract
Autoimmune hepatitis is a corticosteroid-responsive liver disease arising consequent to immunogenetic and environmental risk factors. The clinical course reflects relapsing and remitting, hepatocyte targeted immunologic damage, which is countered by reparative responses to cell injury. Appropriate and timely immunosuppressive therapy drives the disease into remission, albeit with inevitable side effects. Many challenges faced in the clinic reflect practice that must capture a heterogeneous disease presentation, course, and treatment response, as well as treatment tolerability. In this Grand Round we appraise the evidence supporting current treatment approaches, address the impact of autoimmune liver disease 'crossover or overlap' presentations, explore important clinical correlates to immune-serological classifiers, and discuss the factors influencing choice of alternative therapy in difficult-to-treat situations.
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Affiliation(s)
- Palak J Trivedi
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), Centre for Liver and Gastroenterology Research, University of Birmingham, UK; Liver Unit, University Hospitals Birmingham, Birmingham, UK; Institute of Immunology and Immunotherapy, University of Birmingham, UK
| | - Stefan G Hubscher
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), Centre for Liver and Gastroenterology Research, University of Birmingham, UK; Liver Unit, University Hospitals Birmingham, Birmingham, UK; Institute of Immunology and Immunotherapy, University of Birmingham, UK; Dept. of Cellular Pathology, University Hospitals Birmingham, UK
| | | | - Dermot Gleeson
- Liver Unit, Sheffield Teaching Hospitals Foundation Trust, UK
| | - Gideon M Hirschfield
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), Centre for Liver and Gastroenterology Research, University of Birmingham, UK; Liver Unit, University Hospitals Birmingham, Birmingham, UK; Institute of Immunology and Immunotherapy, University of Birmingham, UK; Toronto Centre for Liver Disease, University of Toronto and University Health Network, Toronto, Canada.
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25
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Kaliyaperumal K, Grove JI, Delahay RM, Griffiths WJH, Duckworth A, Aithal GP. Pharmacogenomics of drug-induced liver injury (DILI): Molecular biology to clinical applications. J Hepatol 2018; 69:948-957. [PMID: 29792895 DOI: 10.1016/j.jhep.2018.05.013] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 05/02/2018] [Accepted: 05/11/2018] [Indexed: 12/14/2022]
Abstract
A 21-year old woman was admitted to hospital with a two-week history of painless jaundice, fatigue and anorexia having previously been fit and well. One month prior to presentation, the patient had taken a five-day course of amoxicillin-clavulanic acid for an infected skin cyst. Otherwise, she was only on the oral contraceptive pill and reported minimal alcohol intake. On examination, she was deeply jaundiced, but alert and oriented with no asterixis. She had no stigmata of chronic liver disease, but hepatomegaly extending 3 cm from below the right subcostal margin was evident. Investigations showed: white cell count 13.4 × 109/L (normal 3.6-9.3), haemoglobin 11.8 g/dl (normal 11-15), platelet count 356 × 109/L (normal 170-420), sodium 138 mmol/L (normal 134-144), potassium 3.5 mmol/L (normal 3.5-5.0), creatinine 32 µmol/L (normal 40-75), albumin 30 g/L (normal 35-48), alanine aminotransferase 707 IU/L (normal 15-54), alkaline phosphatase 151 IU/L (normal 30-130), bilirubin 384 µmol/L (normal 7-31) and prothrombin time 27.2 s (normal 11.7-14). Screening for hepatitis A, B, C, E, Epstein-Barr virus, cytomegalovirus and autoimmune hepatitis was negative. Tests for anti-smooth muscle, antinuclear, and anti-liver-kidney microsomal-1 antibodies were negative; immunoglobulin levels and ceruloplasmin levels were normal. Liver ultrasonography demonstrated a liver of normal contour with no biliary dilatation, a normal spleen size and patent vessels. Liver biopsy revealed severe portal interface hepatitis with lobular inflammation and scant plasma cells. Her clinical condition deteriorated in the following days with prothrombin time and bilirubin rising to 56.6 s and 470 µmol/L, respectively. At follow-up after 11 days, her alanine aminotransferase level was 1,931 IU/L. She developed grade 2 hepatic encephalopathy 14 days after presentation, and was listed for a super-urgent liver transplant. Human leucocyte antigen (HLA) typing was performed as a part of preparatory investigations and showed the patient carried the HLA haplotype HLA-DRB1∗15:02-DQB1∗06:01. Following orthotopic transplantation of a deceased donor graft her explant histology revealed severe ongoing hepatitis with multi-acinar necrosis (Fig. 1A and B). This case raised a number of important questions about the diagnosis of drug-induced liver injury and tools available for clinicians to make the best decisions for patient care: In this Grand Rounds article, we will explore these questions, describing the pathophysiology, diagnostic and prognostic biomarkers, and clinical management of drug-induced liver injury. We will also discuss ongoing areas of uncertainty.
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Affiliation(s)
- Kalaiyarasi Kaliyaperumal
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore
| | - Jane I Grove
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK; Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
| | - Robin M Delahay
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK; Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
| | | | - Adam Duckworth
- Department of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Guruprasad P Aithal
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK; Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK.
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