Tavabie OD, Karvellas CJ, Salehi S, et al. - In the western world, the commonest cause of acute liver failure (ALF) is acetaminophen (APAP) induced ALF. In their previous work, researchers had described correlation of a microRNA signature with successful regeneration post auxiliary liver transplant and recovery from APAP-ALF, so they used this signature to generate microRNA outcome prediction models for APAP-ALF. A nested, case-control study was conducted utilizing serum samples from 194 patients with APAP-ALF enrolled in the US ALF Study Group registry (1998-2014) at early (day 1-2) and late (day 3-5) time-points. They identified limited prognostic value of individual microRNA when utilized in isolation. However, their clinical utility increases when incorporated within microRNA-based outcome prediction models. Observations revealed dynamic miRNA expression across the course of acute liver failure. A regeneration-linked miRNA signature at days 1-2, as well as a cell-death linked miRNA signature at days 3-5, discriminates 21-day mortality. Integration of MELD score and vasopressor use led to improvement in performance of each of these signatures. The early model with clinical variables performed better that other outcome prediction models.