Gamma-Glutamyl Transferase at the Crossroads of Cardiometabolic Disease and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Abstract

Gamma-glutamyltransferase (GGT) is traditionally recognized as a sensitive marker of hepatobiliary dysfunction, but emerging evidence indicates that it is a key mediator between metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic disease (CMD). This review explores the transformation of GGT from a passive diagnostic indicator into a systemic pro-oxidant driver and prognostic marker. GGT's role extends well beyond the gamma-glutamyl cycle. GGT triggers the catabolism of extracellular glutathione and, in the presence of transition metals, produces reactive oxygen species and initiates the development of atherosclerotic plaque. Clinical evidence significantly supports this mechanism. GGT levels correlate closely with markers of systemic inflammation and multiorgan dysfunction. Elevated GGT is associated with an increased risk of early-onset coronary artery disease and sustained cardiovascular mortality.