Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

Simon Pape; Romée J A L M Snijders; Tom J G Gevers; Oliver Chazouilleres; George N Dalekos; Gideon M Hirschfield; Marco Lenzi; Michael Trauner; Michael P Manns; John M Vierling; Aldo J Montano-Loza; Ansgar W Lohse; Christoph Schramm; Joost P H Drenth; Michael A Heneghan; International Autoimmune Hepatitis Group (IAIHG) collaborators(‡)

doi:10.1016/j.jhep.2021.12.041

Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

J Hepatol. 2022 Apr;76(4):841-849. doi: 10.1016/j.jhep.2021.12.041. Epub 2022 Jan 20.

Authors

Simon Pape¹, Romée J A L M Snijders¹, Tom J G Gevers², Oliver Chazouilleres³, George N Dalekos⁴, Gideon M Hirschfield⁵, Marco Lenzi⁶, Michael Trauner⁷, Michael P Manns⁸, John M Vierling⁹, Aldo J Montano-Loza¹⁰, Ansgar W Lohse¹¹, Christoph Schramm¹², Joost P H Drenth¹, Michael A Heneghan¹³; International Autoimmune Hepatitis Group (IAIHG) collaborators(‡)

Collaborators

International Autoimmune Hepatitis Group (IAIHG) collaborators(‡):
P Almasio, F Alvarez, R Andrade, C Arikan, D Assis, E Bardou-Jacquet, M Biewenga, E Cancado, N Cazzagon, O Chazouillères, G Colloredo, M Cuarterolo, G Dalekos, D Debray, M Robles-Díaz, J Drenth, J Dyson, C Efe, B Engel, S Ferri, R Fontana, N Gatselis, A Gerussi, E Halilbasic, N Halliday, M Heneghan, G Hirschfield, B van Hoek, M Hørby Jørgensen, G Indolfini, R Iorio, S Jeong, D Jones, D Kelly, N Kerkar, F Lacaille, C Lammert, B Leggett, M Lenzi, C Levy, R Liberal, A Lleo, A Lohse, S Ines Lopez, E de Martin, V McLin, G Mieli-Vergani, P Milkiewicz, N Mohan, L Muratori, G Nebbia, C van Nieuwkerk, Y Oo, A Ortega, A Páres, T Pop, D Pratt, T Purnak, G Ranucci, S Rushbrook, C Schramm, A Stättermayer, M Swain, A Tanaka, R Taubert, D Terrabuio, B Terziroli, M Trauner, P Valentino, F van den Brand, A Villamil, S Wahlin, H Ytting, K Zachou, M Zeniya

Affiliations

¹ Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).
² Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands; Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht 6229HX, The Netherlands; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).
³ Hepatology Department, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, Saint-Antoine Hospital Assistance Publique-Hôpitaux de Paris, Paris, France; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).
⁴ Department of Medicine and Research Laboratory of Internal Medicine, University of Thessaly Medical School, Larissa, Greece.
⁵ Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Canada.
⁶ Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy.
⁷ Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).
⁸ Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).
⁹ Departments of Medicine and Surgery, Baylor College of Medicine, Houston, TX, USA.
¹⁰ Division of Gastroenterology and Hepatology, University of Alberta Hospital, Edmonton, Canada.
¹¹ 1(st) Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).
¹² 1(st) Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).
¹³ Institute of Liver Studies, King's College Hospital, London, United Kingdom; European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Electronic address: [email protected].

PMID: 35066089
DOI: 10.1016/j.jhep.2021.12.041

Abstract

Background & aims: Autoimmune hepatitis (AIH) has been well characterised and codified through the development of diagnostic criteria. These criteria have been adapted and simplified and are widely used in clinical practice. However, there is a need to update and precisely define the criteria for both treatment response and treatment.

Methods: A systematic review was performed and a modified Delphi consensus process was used to identify and redefine the response criteria in autoimmune hepatitis.

Results: The consensus process initiated by the International Autoimmune Hepatitis Group proposes that the term 'complete biochemical response' defined as 'normalization of serum transaminases and IgG below the upper limit of normal' be adopted to include a time point at 6 months after initiation of treatment. An insufficient response by 6 months was a failure to meet the above definition. Non-response was defined as '<50% decrease of serum transaminases within 4 weeks after initiation of treatment'. Remission is defined as liver histology with a Hepatitis Activity Index <4/18. Intolerance to treatment was agreed to stand for 'any adverse event possibly related to treatment leading to potential drug discontinuation'.

Conclusions: These definitions provide a simple and reproducible framework to define treatment response and non-response, irrespective of the therapeutic intervention. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable inter-study comparisons. Future prospective database studies are needed to validate these endpoints.

Lay summary: Consensus among international experts on response criteria and endpoints in autoimmune hepatitis is lacking. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable the comparison of results between clinical trials. Therefore, the International Autoimmune Hepatitis Group (IAIHG) herein presents a statement on 5 agreed response criteria and endpoints: complete biochemical response, insufficient response, non-response, remission, and intolerance to treatment, which can be used to guide future reporting.

Keywords: autoimmune hepatitis; complete biochemical response; endpoints; insufficient response; intolerance; non-response; remission.

Publication types

Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Hepatitis, Autoimmune* / diagnosis
Hepatitis, Autoimmune* / drug therapy
Humans
Prospective Studies
Transaminases

Substances

Transaminases