Utilization of the Disease Severity Index (DSI) from the HepQuant DuO Test Enhances Clinical Decision Making in Compensated Advanced Chronic Liver Disease

<b>Background/Objectives:</b> Compensated advanced chronic liver disease (cACLD) affects millions and carries risk for portal hypertension, large varices, and clinical decompensation. The HepQuant DuO^® test provides a blood-based assessment of liver function and physiology, generating a disease severity index (DSI) validated for risk stratification. A retrospective, real-world, observational analysis was conducted to evaluate the utility of HepQuant DuO's DSI cutpoint (18.3) in guiding endoscopy and clinical management decisions for patients with cACLD in the United States. <b>Methods:</b> De-identified data from 87 cases with cACLD were extracted from physician-provided Statements of Medical Necessity documenting the reasons for the HepQuant DuO test. The primary endpoint was concordance of endoscopy decisions with DSI ≤ 18.3 (avoid) or >18.3 (proceed). The secondary endpoint was concordance of clinical management intensity with the same cutpoint. <b>Results:</b> Among the 55 cases analyzed for endoscopy decisions, overall concordance with DSI 18.3 was 93% (<i>p</i> < 0.001 by Fisher's exact test): 96% of cases with DSI ≤ 18.3 avoided endoscopy, and 90% with DSI > 18.3 underwent endoscopy. For the 45 cases assessing management intensity, overall concordance was 89% (<i>p</i> < 0.001): 90% of cases with DSI ≤ 18.3 had reduced follow-up, and 89% with DSI > 18.3 had intensified management. The cohort exhibited broad functional heterogeneity not captured by standard labs or elastography. <b>Conclusions:</b> HepQuant DuO's DSI cutpoint 18.3 demonstrated strong concordance with real-world clinical decisions, supporting its utility for risk stratification, optimizing endoscopy use, and tailoring management in cACLD.