Occurrence of hypoxic liver injury in patients with acute respiratory distress syndrome: A retrospective cohort study

Hypoxic liver injury (HLI) is a frequent and life-threatening complication occurring in up to 10% of critically ill patients. HLI can be typically found in a setting of cardiac, circulatory, or respiratory failure. Data regarding the occurrence, course, and outcome of HLI in acute respiratory distress syndrome (ARDS) is scarce. This study aimed to investigate the incidence, clinical characteristics, and outcome of HLI in critically ill, mechanically ventilated patients with ARDS. This is a single-center, retrospective observational study conducted at the intensive care units (ICUs) of a tertiary-care university hospital in Hamburg, Germany from December 1, 2017 to April 30, 2021. It includes all consecutive critically ill adult patients who met the Berlin Definition criteria for moderate or severe ARDS and required invasive mechanical ventilation within 48 h of ICU admission and for more than 48 h. Clinical course characteristics and key laboratory markers were systematically compared and analyzed according to HLI diagnostic status across all enrolled patients. HLI was defined according to established criteria as elevation of aminotransferase levels (>20-fold upper-limit-of-normal). Predictors of HLI occurrence, clinical course, and outcome were assessed. In total, 434 critically ill patients with ARDS were included. During the ICU stay, 22.4% ( n =97) developed HLI. Baseline characteristics including age, sex, and body mass index were comparable between patients with and without HLI. The median Charlson Comorbidity Index was comparable in both groups (3 vs. 3 points; P =0.36). A higher disease severity on admission represented by the sequential organ failure assessment (SOFA) score was observed in patients with HLI (11 vs. 10 points; P <0.001). The median arterial partial pressure of oxygen (PaO 2 )/ fraction of inspired oxygen (FiO 2 ) ratio was 81 mmHg (interquartile range [IQR]: 60–109 mmHg) in patients with HLI compared to 79 mmHg (IQR: 60–106 mmHg) in patients without HLI, respectively ( P =0.900). Overall, 35.0% ( n =152) of patients required veno-venous extracorporeal membrane oxygenation therapy, including 39.2% ( n =38) within the HLI group and 33.8% ( n =114) without HLI. The incidence of renal replacement therapy (RRT) was 87.6% ( n =85) among patients with HLI and 53.1% ( n =179) among those without HLI ( P <0.001). ICU mortality was 74.2% ( n =72) and 58.2% ( n =196) in the patients with or without HLI, respectively ( P <0.001). Regression analysis identified cholestasis (odds ratio [OR]=2.061, 95% confidence interval [CI]: 1.220 to 3.481, P <0.010) and RRT (OR=4.732, 95% CI: 2.416 to 9.267, P <0.001) as factors significantly associated with new-onset HLI. Occurrence of HLI was independently associated with mortality (hazard ratio [HR]=1.710, 95% CI: 1.273 to 2.297, P <0.001). HLI is a common condition in critically ill patients with ARDS, and its occurrence is highly associated with mortality. HLI may serve as prognostic marker in critically ill patients with ARDS.