CK-18 cell death markers improve the prediction of histological remission in autoimmune hepatitis during biochemical remission

Abstract

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.