Discovery of biophysical rate laws from the electronic health record enables real-time liver injury estimation from transaminase dynamics.

Abstract

Alanine (ALT) and aspartate (AST) aminotransferases are standard-of-care biomarkers for liver injury though their temporal dynamics during injury and resolution remain incompletely characterized. Here, we analyze aminotransferase kinetics to determine whether rate laws can be ascertained during acute liver injury agnostic to etiology. From 6.5 million AST and ALT measurements in 91,086 patients, we identify a single rate-limiting step in transaminase decline enabling the discovery of plasma clearance rates of AST (1.13 days^-1) and ALT (0.47 days^-1). These rates highlight that transaminases lag real-time liver injury on timescales relevant to clinical decision-making. To resolve this delay, we introduce a correction for AST and ALT, the hepatocyte injury index (HIX, hix.massgeneral.org), which yields a real-time estimate of liver injury. For both liver biopsies and choledocholithiasis, the HIX better distinguishes persistent versus resolved liver injury than transaminase values alone. The HIX can enable more timely clinical decisions for patients with acute liver injury.