Subphenotypes and the De Ritis ratio for mortality risk stratification in sepsis-associated acute liver injury

\(\bf Background\) Sepsis-associated liver injury (SALI) is associated with poor outcomes and increased mortality. However, effectively stratifying SALI patients according to prognosis remains challenging. This study evaluates laboratory-based clustering filters for stratifying SALI patients by 30-day mortality risk, utilizing data mining techniques for novel pattern discovery. \(\bf Methods\) This retrospective cohort study analyzed SALI patients from two ICU databases: Medical Information Mart for Intensive Care (MIMIC)-IV database (n = 73,181, study period: 2008 to 2019) and Amsterdam UMC (n = 16,194, study period: 2003 to 2016). Patients were identified using Sepsis-3 criteria and liver injury markers. Risk stratification employed three laboratory-based approaches: (I) De Ritis ratio (aspartate aminotransferase/alanine aminotransferase), (II) R-factor (alanine aminotransferase and alkaline phosphatase relative to their upper limits of normal), and (III) alanine aminotransferase elevation. Kaplan–Meier analysis and multivariable Cox regression assessed the association between stratification methods and 30-day mortality risk. \(\bf Findings\) SALI patients had almost a 2-fold higher risk of 30-day mortality than those without SALI (hazard ratio: 1.73; 95%-CI: 1.58–1.90, p < 0.0001). Each stratification method (I-III) successfully classified patients into statistically distinct risk strata. The De Ritis ratio emerged as the strongest prognostic differentiation method: a ratio \(\leq\)1 indicated no significant increase in mortality risk (hazard ratio: 0.86; 95%-CI: 0.68–1.09, p = 0.21), whereas ratios of 1–2 and \(\geq\)2 were significantly associated with higher mortality (hazard ratio: 1.56; 95%-CI: 1.37–1.78, p < 0.0001 and hazard ratio: 2.46; 95%-CI: 2.18–2.77, p < 0.0001, respectively). All findings were confirmed in the validation cohort. \(\bf Interpretation\) The De Ritis ratio serves as a valuable prognostic tool for 30-day mortality in SALI patients. Our findings indicate that patients with a ratio \(\geq\)1 face significantly worse outcomes, highlighting the need for targeted interventions. These results refine risk stratification in SALI subphenotypes, enhancing our understanding of its prognostic implications.