Admission Liver Injury Is an Independent Predictor of Early and Overall Mortality in Hospitalized Patients with Moderate-to-Critical COVID-19: A Retrospective Cohort Study

Background: Liver injury (LI) is frequently observed in patients with COVID-19, particularly in severe forms of disease. However, its prognostic significance remains incompletely defined. Aim: To evaluate the association between LI at admission and clinical outcomes in hospitalized patients with moderate, severe, and critical COVID-19. Methods: This single-centre retrospective cohort study included 816 adults hospitalized with moderate-to-critical COVID-19 at a tertiary care hospital in Romania. LI was defined as elevations ≥ 2× the upper limit of normal (ULN) in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), or total bilirubin (TB) at admission. Clinical, laboratory, imaging, and outcome data, including intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and mortality, were analysed. Results: LI was present in 34.9% of patients. Compared with patients without LI, affected patients more frequently exhibited inflammatory syndrome (98.7% vs. 95.2%, p = 0.017), elevated interleukin-6 (IL-6) levels (65.3% vs. 44.3%, p = 0.007), and extensive pulmonary involvement (>75% on chest computed tomography; 38.2% vs. 27.3%, p = 0.003). They were also more likely to require ICU admission (44.2% vs. 36.2%, p = 0.025) and IMV (30.9% vs. 23.5%, p = 0.011). Seven-day mortality (25.9% vs. 16.1%, p = 0.001) and overall mortality (49.8% vs. 36.8%, p < 0.001) were significantly higher among patients with LI. In multivariable analysis, LI remained independently associated with both 7-day and overall mortality. The association between admission LI and mortality remained consistent across pandemic waves, with no significant interaction between liver injury and wave (p = 0.731). Conclusions: LI at admission may help identify patients with COVID-19 at increased risk of adverse outcomes and represents a simple and widely available tool for early risk stratification and clinical management.