Profiles of mi RNA RNA s in serum in severe acute drug induced liver injury and their prognostic significance

摘要

Abstract Background & Aims Drug induced liver injury ( DILI ) is challenging because of the lack of biomarkers to predict mortality. Our aim was to describe miRNA changes in sera of subjects with acute idiosyncratic DILI and determine if levels of miRNAs were associated with 6?month mortality. Methods Clinical data and sera were collected from subjects enrolled in the Drug Induced Liver Injury Network prospective study. mi RNA s were isolated from serum obtained from 78 subjects within 2?weeks of acute DILI and followed up for 6?months or longer. mi RNA s were compared to 40 normal controls and 6?month survivors vs non‐survivors. Results The mean age of the DILI cohort was 48?years, and 55% were female. Eleven (14.1%) subjects died, 10 within 6?months of DILI onset, 5 (45%) liver related. Lower levels of mi RNA s‐122, ‐4463 and ‐4270 were associated with death within 6?months ( P .05). None of the subjects with mi RNA ‐122 greater than the median value died within 6?months for a sensitivity of 100% and specificity of 57%. In subjects with a serum albumin 2.8?g/dL and miR‐1227.89 RFU the sensitivity, specificity, positive and negative predictive values for death within 6?months were 100%, 57%, 38% and 100% respectively. Conclusions Serum mi RNA ‐122 combined with albumin accurately identified subjects who died within 6?months of drug induced liver injury. If confirmed prospectively, mi RNA ‐122 and albumin may be useful in identifying patients at high risk for mortality or liver transplantation.