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De Ritis Ratio and Heparin Therapy in Sepsis-Associated Liver Injury: A Multicenter Cohort Study.

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Unfractionated heparin (UFH) reduces mortality in sepsis-associated liver injury (SALI). While the De Ritis ratio (DRR) identifies high-risk patients, it does not predict UFH response, necessitating further trials.

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Area of Science:

  • Critical Care Medicine
  • Hepatology
  • Pharmacology

Background:

  • Sepsis-associated liver injury (SALI) is a complex thromboinflammatory condition lacking targeted treatments.
  • The De Ritis ratio (DRR) aids in stratifying mortality risk in SALI.
  • Unfractionated heparin (UFH) has anti-thromboinflammatory properties with potential therapeutic value in SALI.

Purpose of the Study:

  • To investigate if the DRR can identify a specific SALI subphenotype that benefits more from UFH therapy.
  • To evaluate the association between UFH treatment and mortality across different DRR strata in SALI patients.

Main Methods:

  • Retrospective analysis of 9,561 SALI patients from MIMIC-IV and eICU-CRD databases.
  • Propensity score matching (PSM) and marginal structural Cox models (MSCM) were used to control for confounders.
  • Subgroup analyses assessed UFH's impact on mortality across DRR levels, including interaction testing.

Main Results:

  • UFH therapy was significantly associated with reduced intensive care unit (ICU) mortality in both cohorts after PSM and MSCM analyses.
  • A numerical trend towards benefit was observed in patients with DRR > 1.
  • Formal tests for interaction between UFH and DRR strata were not statistically significant in either cohort.

Conclusions:

  • UFH therapy is linked to decreased mortality in patients with SALI.
  • While DRR identifies a high-risk group, it is not a reliable predictive biomarker for UFH response in SALI.
  • Further prospective randomized trials are required to confirm these findings and explore DRR-stratified UFH benefits.