External Validation of Laboratory-Based Models to Assess Portal Hypertension Severity in Patients with Compensated Chronic Liver Disease

Purpose Non-invasive laboratory-based models have been proposed to estimate portal hypertension severity in patients with compensated advanced chronic liver disease (cACLD), but external validation in diverse populations remains limited. We aimed to externally validate two such models, originally developed in European cohorts, for predicting clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥ 10 mmHg) and severe portal hypertension (HVPG ≥ 16 mmHg) in a U.S.-based cACLD cohort. Methods We conducted a retrospective single-center study of adults with cACLD who underwent HVPG measurement between 2014 and 2024. Patients with active hepatic decompensation, hepatocellular carcinoma, or prior transjugular intrahepatic portosystemic shunt were excluded. Model performance of the Vienna laboratory-based model and the FIB-4 plus albumin (FIB4+) model was evaluated using discrimination (area under the receiver operating characteristic curve [AUROC]) and calibration metrics, including calibration intercepts, slopes, and Brier scores. Results The cohort included 143 patients (median age 56 years; 54% female), predominantly with metabolic dysfunction–associated steatotic liver disease or alcohol-related liver disease. Median HVPG was 7 mmHg, with CSPH present in 33% and HVPG ≥ 16 mmHg in 11%. Discrimination was modest for both models. The Vienna model achieved AUROCs of 0.71 for HVPG ≥ 10 mmHg and 0.77 for HVPG ≥ 16 mmHg, while the FIB4 + model achieved AUROCs of 0.69 and 0.71, respectively. Both models systematically overestimated risk, demonstrating poor calibration across thresholds. Negative predictive values for HVPG ≥ 16 mmHg exceeded 95% for both models. Predictive performance was weaker in non-viral etiologies. Conclusion In this U.S.-based external validation, laboratory-based models for portal hypertension showed modest discrimination and poor calibration, with systematic risk overestimation. While high negative predictive values suggest potential utility as rule-out tools for severe portal hypertension, recalibration and prospective validation are required before clinical implementation.