DOI: 10.1097/hep.0000000000000829 ISSN: 0270-9139

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

Georg Semmler, Lukas Hartl, Yuly Paulin Mendoza, Benedikt Simbrunner, Mathias Jachs, Lorenz Balcar, Michael Schwarz, Benedikt Silvester Hofer, Laurenz Fritz, Anna Schedlbauer, Katharina Stopfer, Daniela Neumayer, Jurij Maurer, Robin Szymanski, Elias Laurin Meyer, Bernhard Scheiner, Peter Quehenberger, Michael Trauner, Elmar Aigner, Annalisa Berzigotti, Thomas Reiberger, Mattias Mandorfer
  • Hepatology
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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.

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