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

TY - JOUR

T1 - Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

AU - Pape, Simon

AU - Snijders, Romée Jalm

AU - Gevers, Tom Jg

AU - Chazouilleres, Oliver

AU - Dalekos, George N

AU - Hirschfield, Gideon M

AU - Lenzi, Marco

AU - Trauner, Michael

AU - Manns, Michael P

AU - Vierling, John M

AU - Montano-Loza, Aldo J

AU - Lohse, Ansgar W

AU - Schramm, Christoph

AU - Drenth, Joost Ph

AU - Heneghan, Michael A

AU - International Autoimmune Hepatitis Group (IAIHG)

N1 - Copyright © 2022. Published by Elsevier B.V.

PY - 2022/4

Y1 - 2022/4

N2 - 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.

AB - 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.

U2 - 10.1016/j.jhep.2021.12.041

DO - 10.1016/j.jhep.2021.12.041

M3 - SCORING: Journal article

C2 - 35066089

VL - 76

SP - 841

EP - 849

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 4

ER -