Derben Finn C, Engel Bastian, Zachou Kalliopi, Hartl Johannes, Hartleben Björn, Bantel Heike, Schramm Christoph, Dalekos George N, Manns Michael P, Jaeckel Elmar, Taubert Richard
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
European Reference Network on Hepatological Diseases (ERN RARE-LIVER).
Liver Int. 2021 Jan;41(1):123-127. doi: 10.1111/liv.14699.
Incomplete histological remission of autoimmune hepatitis (AIH) is associated with a reduced long-term survival and an increased relapse rate even during biochemical remission (BR). The aim of this international multicentre study was to explore the diagnostic fidelity of cytokeratin-18 cell death markers to noninvasively detect incomplete histological remission. Thereby, cytokeratin-18 cell death marker M65 but not ALT and immunoglobulins was significantly higher in patients with incomplete histological remission (mHAI ≥ 4) compared to those with mHAI ≤ 3. M65 levels > 305 U/L, identified in the training cohort, facilitated the noninvasive detection of incomplete histological remission with a sensitivity of 75% and negative predictive value of 86% in the validation cohort. While BR with M65 < 305 U/L suggested complete histological remission (86%), BR with M65 > 305 U/L reduced the rate of histological remission to 60%. In conclusion, M65 may help to better select patients for or to reduce surveillance liver biopsies in the future.
自身免疫性肝炎（AIH）组织学缓解不完全与长期生存率降低及复发率增加相关，即便在生化缓解（BR）期间亦是如此。这项国际多中心研究的目的是探讨细胞角蛋白-18细胞死亡标志物对非侵入性检测组织学缓解不完全的诊断准确性。因此，与mHAI≤3的患者相比，组织学缓解不完全（mHAI≥4）的患者中细胞角蛋白-18细胞死亡标志物M65显著升高，而谷丙转氨酶（ALT）和免疫球蛋白则不然。在训练队列中确定的M65水平>305 U/L有助于非侵入性检测组织学缓解不完全，在验证队列中的敏感性为75%，阴性预测值为86%。当M65<305 U/L时生化缓解提示组织学完全缓解（86%），而M65>305 U/L时生化缓解则使组织学缓解率降至60%。总之，M65可能有助于未来更好地选择患者或减少监测性肝活检。
