Heat stroke–induced liver injury: mechanistic insights, immune dynamics, and emerging therapeutic targets

Heat stroke is a life-threatening heat-related emergency that often leads to multiple organ dysfunction syndrome (MODS), with liver injury among its most prominent manifestations. HS-associated acute liver injury (HS-ALI) is a major determinant of prognosis, yet its pathogenesis remains incompletely understood. Current evidence suggests that HS-ALI results from the interplay of direct thermal stress, systemic inflammation, oxidative imbalance, coagulation dysfunction, and regulated cell death. Emerging experimental studies have implicated pyroptosis, ferroptosis, necroptosis, and gut–liver immune crosstalk in HS-associated tissue injury; however, the strength of evidence varies considerably among these mechanisms, and direct validation in human HS-ALI remains limited. Accordingly, these pathways should be considered potential contributors to disease progression rather than uniformly established mechanisms.