Pape Simon, Snijders Romée J A L M, Gevers Tom J G, Chazouilleres Oliver, Dalekos George N, Hirschfield Gideon M, Lenzi Marco, Trauner Michael, Manns Michael P, Vierling John M, Montano-Loza Aldo J, Lohse Ansgar W, Schramm Christoph, Drenth Joost P H, Heneghan Michael A
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).
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).
J Hepatol. 2022 Apr;76(4):841-849. doi: 10.1016/j.jhep.2021.12.041. Epub 2022 Jan 20.
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.
A systematic review was performed and a modified Delphi consensus process was used to identify and redefine the response criteria in autoimmune hepatitis.
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'.
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.
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.
通过制定诊断标准，自身免疫性肝炎（AIH）已得到充分的特征描述和规范。这些标准经过调整和简化，在临床实践中广泛应用。然而，需要更新并精确界定治疗反应和治疗的标准。
进行了一项系统综述，并采用改良的德尔菲共识法来识别和重新定义自身免疫性肝炎的反应标准。
国际自身免疫性肝炎小组发起的共识过程提议采用“完全生化反应”这一术语，定义为“血清转氨酶和IgG恢复正常，且低于正常上限”，并纳入治疗开始后6个月这一时间点。治疗6个月时反应不足是指未达到上述定义。无反应定义为“治疗开始后4周内血清转氨酶下降幅度<50%”。缓解定义为肝组织学检查的肝炎活动指数<4/18。治疗不耐受被认定为“任何可能与治疗相关的不良事件，导致可能停用药物”。
这些定义提供了一个简单且可重复的框架，用于界定治疗反应和无反应，而不论治疗干预措施如何。迫切需要就终点达成共识，以设定研究结果报告的全球标准，并实现研究间的比较。未来需要进行前瞻性数据库研究来验证这些终点。
国际专家在自身免疫性肝炎的反应标准和终点方面缺乏共识。迫切需要就终点达成共识，以设定研究结果报告的全球标准，并实现临床试验结果之间的比较。因此，国际自身免疫性肝炎小组（IAIHG）在此提出关于5个已达成共识的反应标准和终点的声明：完全生化反应、反应不足、无反应、缓解和治疗不耐受，可用于指导未来的报告。
