Hypoxic Hepatitis in Critically Ill Patients: Incidence, Clinical Characteristics, and Outcomes — A Systematic Review and Meta-Analysis

Background Hypoxic hepatitis (HH), also termed ischemic hepatitis and historically described as shock liver, is an acute liver injury syndrome in critically ill patients characterized by a rapid and marked rise in aminotransferases in the setting of circulatory, cardiac, or respiratory failure, after exclusion of other causes of acute hepatic injury. Despite its clinical relevance, the true incidence and prognostic significance of HH remain unclear. This systematic review and meta-analysis aimed to determine the pooled incidence, mortality, and outcomes of HH in critically ill patients. Methods This study followed PRISMA guidelines and was registered in PROSPERO (CRD420251088120). A systematic search of PubMed, Scopus, Web of Science, EMBASE, Cochrane, LILACS, CNKI, and Google Scholar was conducted on July 4, 2025. Randomized, cohort, and case-control studies involving critically ill adults were included. Primary outcomes were HH incidence and mortality; secondary outcomes included length of stay, organ support, and comparisons with non-HH patients. Random-effects meta-analyses were performed, with heterogeneity assessed using I 2 statistics. Results Of 3236 records, 25 studies (150,928 patients) met inclusion criteria. The pooled prevalence of HH in ICU patients was 8.3%, and all-cause mortality was 64.0%. Compared with non-HH patients, HH was associated with higher all-cause mortality (RR 2.94). Mechanical ventilation (RR 2.44) and renal replacement therapy (RR 3.80) showed elevated but statistically non-significant associations. Cardiogenic shock, cardiac arrest, and sepsis were the leading reported precipitants. Conclusion HH affects a substantial proportion of ICU patients and is consistently associated with adverse outcomes and greater organ support use. However, the available evidence supports HH primarily as an associated prognostic marker rather than a proven causal determinant of mortality. Findings should be interpreted cautiously because of high heterogeneity, potential residual confounding, and possible publication bias. Standardized diagnostic criteria and prospective studies evaluating incremental prognostic value beyond established ICU severity scores are needed.