Simple blood tests to diagnose compensated advanced chronic liver disease and stratify risk of clinically significant portal hypertension.

BACKGROUND AIMS: Compensated advanced chronic liver disease (cACLD) identifies patients at risk for clinically significant portal hypertension (CSPH), and thus, for liver-related complications. Limited availability of liver stiffness measurements (LSM) impedes the identification of patients at risk for cACLD/CSPH outside of specialized clinics. We aimed to develop a blood-based algorithm to identify cACLD by FIB-4 and CSPH by von Willebrand factor/platelet count ratio (VITRO).

APPROACH RESULTS: Patients with (suspected) compensated chronic liver disease undergoing FIB4+LSM were included in the LSM/FIB-4-cohorts from Vienna&Salzburg. The HVPG/VITRO-cohorts included patients undergoing hepatic venous pressure gradient (HVPG)-measurement+VITRO from Vienna&Bern.LSM/FIB-4-derivation-cohort: We included 6143 patients of whom 211 (3.4%) developed hepatic decompensation. 1724 (28.1%) had LSM ≥10 kPa, which corresponded to FIB-4≥1.75. Importantly, both LSM (AUROC:0.897 [95%CI:0.865-0.929]) and FIB-4 (AUROC:0.914 [95%CI:0.885-0.944]) were similarly accurate in predicting hepatic decompensation within 3 years. FIB-4≥1.75 identified patients at risk for first hepatic decompensation (5y-cumulative incidence:7.6%), while in those <1.75, risk was negligible (0.3%).HVPG/VITRO-derivation-cohort: 247 patients of whom 202 had cACLD/FIB-4≥1.75 were included. VITRO exhibited an excellent diagnostic performance for CSPH (AUROC:0.889 [95%CI:0.844-0.934]), similar to LSM (AUROC:0.856 [95%CI:0.801-0.910], p=0.351) and the ANTICIPATE model (AUROC:0.910 [95%CI:0.869-0.952], p=0.498). VITRO<1.0/≥2.5 ruled-out (sensitivity:100.0%)/ruled-in (specificity:92.4%) CSPH. The diagnostic performance was comparable to Baveno-VII criteria.LSM/FIB-4-derivation-cohort findings were externally validated in n=1560 patients, while HVPG/VITRO-derivation-cohort findings were internally (n=133) and externally (n=55) validated.

CONCLUSION: Simple, broadly available laboratory tests (FIB-4/VITRO) facilitate cACLD detection and CSPH risk stratification in patients with (suspected) liver disease. This blood-based approach is applicable outside of specialized clinics and may promote early intervention.