Fiore M, Cosenza G, Coppolino F, Pota V, Sansone P, Petrou S, Pace MC. Hypertransaminasemia in non-cirrhotic critically-ill patients. World J Hepatol 2025; 17(11): 109645 [DOI: 10.4254/wjh.v17.i11.109645]
Corresponding Author of This Article
Marco Fiore, MD, Lecturer, Professor, Department of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, Naples 80138, Campania, Italy. marco.fiore@hotmail.it
Research Domain of This Article
Critical Care Medicine
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Nov 27, 2025; 17(11): 109645 Published online Nov 27, 2025. doi: 10.4254/wjh.v17.i11.109645
Hypertransaminasemia in non-cirrhotic critically-ill patients
Marco Fiore, Gianluigi Cosenza, Francesco Coppolino, Vincenzo Pota, Pasquale Sansone, Stephen Petrou, Maria C Pace
Marco Fiore, Gianluigi Cosenza, Francesco Coppolino, Vincenzo Pota, Pasquale Sansone, Maria C Pace, Department of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Campania, Italy
Stephen Petrou, Department of Emergency Medicine, Queen’s North Hawaii Community Hospital, Waimea, HI 96743, United States
Co-first authors: Marco Fiore and Gianluigi Cosenza.
Author contributions: Fiore M and Cosenza G designed the study, they contributed equally to this article, they are the co-first authors of this manuscript; Coppolino F, Pota V, and Sansone P performed the search; Pace MC supervised the manuscript; Petrou S revised the manuscript to improve and polish language; Fiore M and Cosenza G wrote the paper; and all authors thoroughly reviewed and endorsed the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marco Fiore, MD, Lecturer, Professor, Department of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, Naples 80138, Campania, Italy. marco.fiore@hotmail.it
Received: May 19, 2025 Revised: June 18, 2025 Accepted: October 10, 2025 Published online: November 27, 2025 Processing time: 194 Days and 19.7 Hours
Abstract
Hypertransaminasemia - acute elevation of alanine aminotransferase and aspartate aminotransferase - is prevalent in non-cirrhotic adults admitted to the intensive care unit (ICU) and often signals extra-hepatic pathophysiology rather than intrinsic liver disease. To synthesise contemporary evidence on aetiology-driven diagnosis, management and emerging biomarkers of hypertransaminasemia in critically ill patients. We performed a structured search of PubMed, EMBASE and CENTRAL (January 2010-June 2025). The search was restricted to full-text articles that were published in English in peer-reviewed journals. Hypoxic liver injury is the leading cause of hypertransaminasemia in non-cirrhotic ICU patients and is characterized by a ≥ 50% alanine aminotransferase/aspartate aminotransferase fall within 72 hours after haemodynamic stabilisation. Idiosyncratic drug-induced liver injury remains uncommon yet explains about 13% of acute liver-failure cases in Western registries. Sepsis-associated liver injury presents mainly as conjugated hyperbilirubinaemia with modest transaminase rise, whereas parenteral-nutrition-associated liver disease is dominated by cholestasis after > 2 weeks of parenteral feeding. Early optimisation of macro-/micro-circulation, rational deprescribing of hepatotoxins, rapid source control of infection and prompt transition to enteral nutrition are outcome-modifying interventions across all phenotypes. In the ICU, aminotransferase elevation should be interpreted as a dynamic biomarker of systemic distress. A pattern-recognition algorithm integrating clinical context, enzyme kinetics and novel biomarkers (glutamate dehydrogenase, microRNA-122, high-mobility group box-1) can expedite aetiology-specific therapy and deserves prospective validation.
Core Tip: Hypertransaminasemia in non-cirrhotic intensive care unit patients is more often the biochemical echo of hypoperfusion, sepsis, drug toxicity or parenteral-nutrition cholestasis than a sign of primary hepatopathy. A structured, pattern-based algorithm - degree of aspartate aminotransferase/alanine aminotransferase rise, timing, haemodynamic milieu and medication exposure - enables rapid discrimination among hypoxic liver injury, drug-induced liver injury, sepsis-associated liver injury and parenteral nutrition-associated liver disease, guides targeted intervention and prevents futile diagnostics. Novel biomarkers such as glutamate dehydrogenase and microRNA-122 provide muscle-independent, early detection of hepatocellular injury and represent the next frontier for precision hepatology in critical care.
