Research gaps and opportunities in autoimmune hepatitis-Results of the international autoimmune hepatitis group research workshop 2022.
autoimmune hepatitis
clinical trials
diagnostics
quality of life
treatment
unmet needs
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
17
03
2023
received:
26
09
2022
accepted:
22
03
2023
medline:
15
6
2023
pubmed:
11
4
2023
entrez:
10
4
2023
Statut:
ppublish
Résumé
Autoimmune hepatitis (AIH) is a rare autoimmune liver disease that is characterised by a chronic inflammatory immune reaction directed against hepatocytes. The disease results in a substantial reduction in quality of life and potentially leads to liver-related complications or death. The International Autoimmune Hepatitis Group (IAIHG) initiated a series of research workshops to uncover the scientific gaps and opportunities in AIH. This review summarises the results of the latest workshop in Maastricht in 2022 and reviews the current challenges in adult AIH, particularly in relation to four important aspects of AIH: diagnostics; new immunomodulatory therapies; clinical trial design; and unmet clinical needs. This review also summarises the progress made since the AIH workshop in 2017. Patients and patient representatives were actively involved in the parallel working groups alongside clinicians and researchers. Despite 40 years of experience with diagnosing and treating AIH, false diagnoses occur and treatment is still based on nonselective immunosuppression. In addition to the need for more specific diagnostic tests, prognostic markers and tailor-based treatments, a major unmet clinical need was identified in areas of care delivery and health-related quality of life.
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1375-1384Informations de copyright
© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.
Références
Trivedi PJ, Hirschfield GM. Recent advances in clinical practice: epidemiology of autoimmune liver diseases. Gut. 2021;70(10):1989-2003.
Snijders RJ, Milkiewicz P, Schramm C, Gevers TJ. Health-related quality of life in autoimmune hepatitis. World J Hepatol. 2021;13(11):1642-1652.
Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D. Autoimmmune hepatitis. Cell Mol Immunol. 2022;19(2):158-176.
Dyson JK, De Martin E, Dalekos GN, et al. Review article: unanswered clinical and research questions in autoimmune hepatitis-conclusions of the international autoimmune hepatitis group research workshop. Aliment Pharmacol Ther. 2019;49(5):528-536.
Oo YH, Ackrill S, Cole R, et al. Liver homing of clinical grade Tregs after therapeutic infusion in patients with autoimmune hepatitis. JHEP Rep. 2019;1(4):286-296.
Schultheiss C, Simnica D, Willscher E, et al. Next-generation Immunosequencing reveals pathological T-cell architecture in autoimmune hepatitis. Hepatology. 2021;73(4):1436-1448.
Lammert C, Chalasani SN, Atkinson EJ, McCauley BM, Lazaridis KN. Environmental risk factors are associated with autoimmune hepatitis. Liver Int. 2021;41(10):2396-2403.
Li Y, Sun Y, Liu Y, et al. Genome-wide meta-analysis identifies susceptibility loci for autoimmune hepatitis type 1. Hepatology. 2022;76(3):564-575.
Galaski J, Weiler-Normann C, Schakat M, et al. Update of the simplified criteria for autoimmune hepatitis: evaluation of the methodology for immunoserological testing. J Hepatol. 2020;74(2):312-320.
Taubert R, Engel B, Diestelhorst J, et al. Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis. Hepatology. 2022;75(1):13-27.
Lohse AW, Sebode M, Bhathal PS, et al. Consensus recommendations for histological criteria of autoimmune hepatitis from the international AIH pathology group: results of a workshop on AIH histology hosted by the European reference network on Hepatological diseases and the European Society of Pathology: results of a workshop on AIH histology hosted by the European reference network on Hepatological diseases and the European Society of Pathology. Liver Int. 2022;42(5):1058-1069.
De Martin E, Coilly A, Chazouilleres O, et al. Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: the SURFASA score. J Hepatol. 2021;74(6):1325-1334.
Lohse AW, Sebode M, Jorgensen MH, et al. Second-line and third-line therapy for autoimmune hepatitis: a position statement from the European reference network on Hepatological diseases and the international autoimmune hepatitis group. J Hepatol. 2020;73(6):1496-1506.
Snijders R, Stoelinga AEC, Gevers TJG, et al. Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial. Trials. 2022;23(1):1012.
Than NN, Hodson J, Schmidt-Martin D, et al. Efficacy of rituximab in difficult-to-manage autoimmune hepatitis: results from the international autoimmune hepatitis group. JHEP Rep. 2019;1(6):437-445.
Pape S, Gevers TJG, Vrolijk JM, et al. Rapid response to treatment of autoimmune hepatitis associated with remission at 6 and 12 months. Clin Gastroenterol Hepatol. 2020;18(7):1609-17 e4.
Biewenga M, Verhelst X, Baven-Pronk M, et al. Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1. United Eur Gastroenterol J. 2021;9(6):662-671.
Pape S, Snijders R, Gevers TJG, et al. Systematic review of response criteria and endpoints in autoimmune hepatitis by the international autoimmune hepatitis group. J Hepatol. 2022;76(4):841-849.
European Association for the Study of the L. EASL clinical practice guidelines: autoimmune hepatitis. J Hepatol. 2015;63(4):971-1004.
Mack CL, Adams D, Assis DN, et al. Diagnosis and Management of Autoimmune Hepatitis in adults and children: 2019 practice guidance and guidelines from the American Association for the Study of Liver Diseases. Hepatology. 2019;72(2):671-722.
Bjornsson ES, Medina-Caliz I, Andrade RJ, Lucena MI. Setting up criteria for drug-induced autoimmune-like hepatitis through a systematic analysis of published reports. Hepatol Commun. 2022;6(8):1895-1909.
Mieli-Vergani G, Vergani D, Baumann U, et al. Diagnosis and Management of Pediatric Autoimmune Liver Disease: ESPGHAN Hepatology committee position statement. J Pediatr Gastroenterol Nutr. 2018;66(2):345-360.
Dalekos GN, Azariadis K, Lygoura V, Arvaniti P, Gampeta S, Gatselis NK. Autoimmune hepatitis in patients aged 70 years or older: disease characteristics, treatment response and outcome. Liver Int. 2021;41(7):1592-1599.
Lee BT, Tana MM, Kahn JA, Dara L. We are not immune: racial and ethnic disparities in autoimmune liver diseases. Hepatology. 2021;74(5):2876-2887.
Slotter C, Van den Brand FF, Lleo A, et al. The international autoimmune hepatitis group retrospective registry: quality assessment and analysis of clinical characteristics and liver-related outcome. J Hepatol. 2022;77(S1):S326.
Alvarez F, Berg PA, Bianchi FB, et al. International autoimmune hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31(5):929-938.
Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008;48(1):169-176.
Johnson PJ, McFarlane IG. Meeting report: international autoimmune hepatitis group. Hepatology. 1993;18(4):998-1005.
Hofer H, Oesterreicher C, Wrba F, Ferenci P, Penner E. Centrilobular necrosis in autoimmune hepatitis: a histological feature associated with acute clinical presentation. J Clin Pathol. 2006;59(3):246-249.
Assis DN. Immunopathogenesis of autoimmune hepatitis. Clin Liver Dis (Hoboken). 2020;15(3):129-132.
Ronca V, Bozward AG, Oo YH. Use of immunosuppression in non-transplant hepatology. Best Pract Res Clin Gastroenterol. 2021;54-55:101760.
Bonito AJ, Aloman C, Fiel MI, et al. Medullary thymic epithelial cell depletion leads to autoimmune hepatitis. J Clin Invest. 2013;123(8):3510-3524.
Bovensiepen CS, Schakat M, Sebode M, et al. TNF-producing Th1 cells are selectively expanded in liver infiltrates of patients with autoimmune hepatitis. J Immunol. 2019;203(12):3148-3156.
Longhi MS, Mieli-Vergani G, Vergani D. Regulatory T cells in autoimmune hepatitis: an updated overview. J Autoimmun. 2021;119:102619.
Schultheiss C, Steinmann S, Lohse AW, Binder M. B cells in autoimmune hepatitis: bystanders or central players? Semin Immunopathol. 2022;44(4):411-427.
Taylor SA, Assis DN, Mack CL. The contribution of B cells in autoimmune liver diseases. Semin Liver Dis. 2019;39(4):422-431.
Wawman RE, Bartlett H, Oo YH. Regulatory T cell metabolism in the hepatic microenvironment. Front Immunol. 2017;8:1889.
Efe C, Hagstrom H, Ytting H, et al. Efficacy and safety of Mycophenolate Mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis. Clin Gastroenterol Hepatol. 2017;15(12):1950-6 e1.
Mack CL, Adams D, Assis DN, et al. Diagnosis and Management of Autoimmune Hepatitis in adults and children: 2019 practice guidance and guidelines from the American Association for the Study of Liver Diseases. Hepatology. 2020;72(2):671-722.
van den Brand FF, van der Veen KS, Lissenberg-Witte BI, et al. Adverse events related to low dose corticosteroids in autoimmune hepatitis. Aliment Pharmacol Ther. 2019;50(10):1120-1126.
Wong LL, Fisher HF, Stocken DD, et al. The impact of autoimmune hepatitis and its treatment on health utility. Hepatology. 2018;68(4):1487-1497.
Renand A, Habes S, Mosnier JF, et al. Immune alterations in patients with type 1 autoimmune hepatitis persist upon standard immunosuppressive treatment. Hepatol Commun. 2018;2(8):968-981.
Robinson S, Thomas R. Potential for antigen-specific Tolerizing immunotherapy in systematic lupus erythematosus. Front Immunol. 2021;12:654701.
Lazar S, Kahlenberg JM. Systemic lupus erythematosus: new diagnostic and therapeutic approaches. Annu Rev Med. 2022;74:339-352.
Sharkey P, Thomas R. Immune tolerance therapies for autoimmune diseases: shifting the goalpost to cure. Curr Opin Pharmacol. 2022;65:102242.
Liberal R, de Boer YS, Heneghan MA. Established and novel therapeutic options for autoimmune hepatitis. Lancet Gastroenterol Hepatol. 2021;6(4):315-326.
Halliday N, Dyson JK, Thorburn D, Lohse AW, Heneghan MA. Review article: experimental therapies in autoimmune hepatitis. Aliment Pharmacol Ther. 2020;52(7):1134-1149.
Jeffery HC, Braitch MK, Bagnall C, et al. Changes in natural killer cells and exhausted memory regulatory T cells with corticosteroid therapy in acute autoimmune hepatitis. Hepatol Commun. 2018;2(4):421-436.
Chen J, Li X, Zeng P, et al. Lamina propria interleukin 17 A aggravates natural killer T-cell activation in autoimmune hepatitis. FASEB J. 2022;36(6):e22346.
Mele D, Bossi G, Maggiore G, et al. Altered natural killer cell cytokine profile in type 2 autoimmune hepatitis. Clin Immunol. 2018;188:31-37.
Richardson N, Wootton GE, Bozward AG, Oo YH. Challenges and opportunities in achieving effective regulatory T cell therapy in autoimmune liver disease. Semin Immunopathol. 2022;44(4):461-474.
Buitrago-Molina LE, Pietrek J, Noyan F, et al. Treg-specific IL-2 therapy can reestablish intrahepatic immune regulation in autoimmune hepatitis. J Autoimmun. 2021;117:102591.
McEachern E, Carroll AM, Fribourg M, et al. Erythropoietin administration expands regulatory T cells in patients with autoimmune hepatitis. J Autoimmun. 2021;119:102629.
Arvaniti P, Giannoulis G, Gabeta S, Zachou K, Koukoulis GK, Dalekos GN. Belimumab is a promising third-line treatment option for refractory autoimmune hepatitis. JHEP Rep. 2020;2(4):100123.
Biewenga M, Heidt S, Vergunst M, et al. B-cell activating factor and IL-21 levels predict treatment response in autoimmune hepatitis. JHEP Rep. 2022;4(5):100460.
Sands BE, Sandborn WJ, Panaccione R, et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2019;381(13):1201-1214.
Boyce EG, Rogan EL, Vyas D, Prasad N, Mai Y. Sarilumab: review of a second IL-6 receptor antagonist indicated for the treatment of rheumatoid arthritis. Ann Pharmacother. 2018;52(8):780-791.
Biggioggero M, Crotti C, Becciolini A, Favalli EG. Tocilizumab in the treatment of rheumatoid arthritis: an evidence-based review and patient selection. Drug Des Devel Ther. 2019;13:57-70.
Weiler-Normann C, Schramm C, Quaas A, et al. Infliximab as a rescue treatment in difficult-to-treat autoimmune hepatitis. J Hepatol. 2013;58(3):529-534.
Chang C, Tanaka A, Bowlus C, Gershwin ME. The use of biologics in the treatment of autoimmune liver disease. Expert Opin Investig Drugs. 2020;29(4):385-398.
Trivedi PJ, Adams DH. Chemokines and chemokine receptors as therapeutic targets in inflammatory bowel disease; pitfalls and promise. J Crohns Colitis. 2018;12(suppl_2):S641-s52.
Nishikawa H, Enomoto H, Iwata Y, et al. B-cell activating factor belonging to the tumor necrosis factor family and interferon-γ-inducible Protein-10 in autoimmune hepatitis. Medicine (Baltimore). 2016;95(12):e3194.
Yellin M, Paliienko I, Balanescu A, et al. A phase II, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of MDX-1100, a fully human anti-CXCL10 monoclonal antibody, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2012;64(6):1730-1739.
Taneja V, El-Dallal M, Haq Z, et al. Effectiveness and safety of Tofacitinib for ulcerative colitis: systematic review and meta-analysis. J Clin Gastroenterol. 2021;56(10):e323-e333.
Wang Y, Wan Z, Jin R, et al. Tofacitinib for extraintestinal manifestations of inflammatory bowel disease: a literature review. Int Immunopharmacol. 2022;105:108517.
Liu C, Wang YL, Yang YY, et al. Novel approaches to intervene gut microbiota in the treatment of chronic liver diseases. FASEB J. 2021;35(10):e21871.
Ma L, Zhang L, Zhuang Y, Ding Y, Chen J. Lactobacillus improves the effects of prednisone on autoimmune hepatitis via gut microbiota-mediated follicular helper T cells. Cell Commun Signal. 2022;20(1):83.
Liang M, Liwen Z, Jianguo S, et al. Fecal microbiota transplantation controls progression of experimental autoimmune hepatitis in mice by modulating the TFR/TFH immune imbalance and intestinal microbiota composition. Front Immunol. 2021;12:728723.
Liwinski T, Heinemann M, Schramm C. The intestinal and biliary microbiome in autoimmune liver disease-current evidence and concepts. Semin Immunopathol. 2022;44(4):485-507.
Manfredo Vieira S, Hiltensperger M, Kumar V, et al. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science. 2018;359(6380):1156-1161.
Umeshappa CS, Singha S, Blanco J, et al. Suppression of a broad spectrum of liver autoimmune pathologies by single peptide-MHC-based nanomedicines. Nat Commun. 2019;10(1):2150.
Pape S, Gevers TJG, Belias M, et al. Predniso(lo)ne dosage and chance of remission in patients with autoimmune hepatitis. Clin Gastroenterol Hepatol. 2019;17(10):2068-75 e2.
Kanzler S, Lohr H, Gerken G, Galle PR, Lohse AW. Long-term management and prognosis of autoimmune hepatitis (AIH): a single center experience. Z Gastroenterol. 2001;39(5):339-341. 44-8.
Pape S, Gevers TJG, Vrolijk JM, et al. High discontinuation rate of azathioprine in autoimmune hepatitis, independent of time of treatment initiation. Liver Int. 2020;40(9):2164-2171.
Lloyd C, Leighton J, Wong LL, et al. Patient priorities in autoimmune hepatitis: the need for better treatments, more education and challenging stigma. Dig Dis Sci. 2022;68(1):87-97.
Orr JG, Homer T, Ternent L, et al. Health related quality of life in people with advanced chronic liver disease. J Hepatol. 2014;61(5):1158-1165.