Simple blood tests to diagnose compensated advanced chronic liver disease and stratify the 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

doi:10.1097/HEP.0000000000000829

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

Hepatology. 2024 Mar 6. doi: 10.1097/HEP.0000000000000829. Online ahead of print.

Authors

Georg Semmler^{1

2}, Lukas Hartl^{1

2}, Yuly Paulin Mendoza^{3

4}, Benedikt Simbrunner^{1

2}, Mathias Jachs^{1

2}, Lorenz Balcar^{1

2}, Michael Schwarz^{1

2}, Benedikt Silvester Hofer^{1

2}, Laurenz Fritz¹, Anna Schedlbauer¹, Katharina Stopfer¹, Daniela Neumayer¹, Jurij Maurer¹, Robin Szymanski¹, Elias Laurin Meyer^{5

6}, Bernhard Scheiner^{1

2}, Peter Quehenberger⁷, Michael Trauner¹, Elmar Aigner⁸, Annalisa Berzigotti^{3

4}, Thomas Reiberger^{1

2}, Mattias Mandorfer^{1

2}

Affiliations

¹ Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
² Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.
³ Department for Visceral Medicine and Surgery, Inselspital, Bern University Hospital, University of Bern, Switzerland.
⁴ Department of Biomedical Research, Visceral Surgery and Medicine, University of Bern, Bern, Switzerland.
⁵ Center for Medical Data Science, Medical University of Vienna, Vienna, Austria.
⁶ Berry Consultants, Vienna, Austria.
⁷ Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
⁸ First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria.

PMID: 38447034
DOI: 10.1097/HEP.0000000000000829

Abstract

Background and aims: Compensated advanced chronic liver disease (cACLD) identifies patients at risk for clinically significant portal hypertension (CSPH), and thus, for liver-related complications. The 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 fibrosis-4 (FIB-4) and CSPH by von Willebrand factor/platelet count ratio (VITRO).

Approach and results: Patients with (suspected) compensated chronic liver disease undergoing FIB-4+LSM were included in the LSM/FIB-4 cohorts from Vienna and Salzburg. The HVPG/VITRO cohorts included patients undergoing HVPG-measurement + VITRO from Vienna and Bern.LSM/FIB-4-derivation-cohort: We included 6143 patients, of whom 211 (3.4%) developed hepatic decompensation. In all, 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 (5 y-cumulative incidence:7.6%), while in those <1.75, the 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 the 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.

Conclusions: 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.