Non-invasive detection of portal hypertension by enhanced liver fibrosis score in patients with different aetiologies of advanced chronic liver disease

Abstract

Background and aims: The enhanced liver fibrosis (ELF) score comprises serum markers of fibrogenesis and matrix remodelling and was developed to detect liver fibrosis, however, it may also be useful for the non-invasive detection of portal hypertension (PHT).

Methods: ELF score and its single components (TIMP1/PIIINP/HA) were analysed in 201 patients with advanced chronic liver disease (ACLD; ie hepatic venous pressure gradient (HVPG) ≥6 mm Hg). Patients with pre-/post-hepatic PHT, hepatocellular carcinoma beyond Milan criteria, and history of TIPS implantation or liver transplantation were excluded.

Results: ELF and its single components correlated with HVPG in the overall cohort: ELF: r = .443, TIMP1: r = .368, PIIINP:r = .332, and HA:r = .419 (all P < .001). The strength of the correlation between ELF and HVPG decreased in higher HVPG strata: 6-9 mm Hg:r = .569(P = .004), 10-19 mm Hg:r = .304 (P = .001) and ≥20 mm Hg:r = -.023(P = .853). Area under the receiver operating characteristics (AUROC) of ELF score to detect clinically significant PHT (CSPH; HVPG ≥ 10 mm Hg) was 0.833. Importantly, HA alone yielded an AUROC of 0.828. Detection of CSPH in strictly compensated ACLD (cACLD) patients was less accurate: AUROC: 0.759 (P < .001). CSPH was ruled-in by ELF ≥ 11.1 with a PPV of 98% (sensitivity: 61%/specificity: 92%/NPV:24%), but CSPH could not be ruled-out. ELF score had a low AUROC of 0.677 (0.60-0.75; P < .001) for the diagnosis of high-risk PHT (HRPH; HVPG ≥ 20mm Hg) and, thus, HRPH could not be ruled-in by ELF. However, ELF < 10.1 ruled-out HRPH with a NPV of 95% (sensitivity: 97%/specificity: 26%/PPV: 39%).

Conclusion: The ELF score correlates with HVPG at values <20 mm Hg. An ELF ≥ 11.1 identifies patients with a high probability of CSPH, while an ELF < 10.1 may be used to rule-out HRPH.

Trial registration: ClinicalTrials.gov NCT03267615.

Keywords: ACLD; advanced chronic liver disease; cirrhosis; clinically significant portal hypertension; hepatic venous pressure gradient; non-invasive; portal hypertension; prediction.

Conflict of interest statement

BeSi received travel support from AbbVie and Gilead. RM received speaker honoraria from Abbott, DiaSorin and Siemens. BeSc received travel support from Abbvie and Gilead. PS received speaking honoraria from Bristol‐Myers Squibb and Boehringer‐Ingelheim, consulting fees from PharmaIN, and travel support from Falk and Phenex Pharmaceuticals. TB received travel support from AbbVie, Bristol‐Myers Squibb, and Medis, as well as speaker fees from Bristol‐Myers Squibb. DB received travel support from Abbvie and Gilead. MP is an investigator for Bayer, BMS, Lilly and Roche; he received speaker honoraria from Bayer, BMS, Eisai and MSD; he is a consultant for Bayer, BMS, Ipsen, Eisai, Lilly, MSD and Roche; he received travel support from Bayer and BMS. MT received speaker fees from BMS, Falk Foundation, Gilead, Intercept and MSD; advisory board fees from Albireo, BiomX, Boehringer Ingelheim, Falk Pharma GmbH, Genfit, Gilead, Intercept, MSD, Novartis, Phenex and Regulus. He further received travel grants from Abbvie, Falk and Gilead and Intercept and unrestricted research grants from Albireo, Cymabay, Falk, Gilead, Intercept, MSD and Takeda. MM has served as a speaker and/or consultant and/or advisory board member for AbbVie, Bristol‐Myers Squibb, Gilead, WL Gore & Associates and Janssen. TR received grant support from Abbvie, Boehringer‐Ingelheim, Gilead, MSD, Philips Healthcare and Gore; speaking honoraria from Abbvie, Gilead, Gore, Intercept and Roche, MSD; consulting/advisory board fee from Abbvie, Bayer, Boehringer‐Ingelheim, Gilead, MSD and Siemens; and travel support from Boehringer‐Ingelheim, Gilead and Roche. AS, EE, RP and AFS declare no conflict of interest.

© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.

Figures

Figure 1

Correlation of enhanced liver fibrosis (ELF) score with hepatic venous pressure gradient (HVPG). Abbreviations: cACLD, compensated advanced chronic liver disease; dACLD, decompensated advanced chronic liver disease; ELF, enhanced liver fibrosis score; HA, hyaluronic acid; HVPG, hepatic venous pressure gradient; mm Hg, millimetres of mercury; PIIINP, amino‐terminal propeptide of type III procollagen; Rho, Spearman's Rho; TIMP‐1, tissue inhibitor matrix metalloproteinase‐1

Figure 2

Area under the receiver operating characteristics (AUROC) for detection of clinically significant portal hypertension (CSPH) and high‐risk portal hypertension (HRPH). (A) CSPH in patients with compensated liver disease (cACLD) and (B) HRPH in the overall cohort. Abbreviations: cACLD, compensated advanced chronic liver disease; CSPH, Clinically significant portal hypertension; ELF, Enhanced liver fibrosis score; HA, Hyaluronic acid; HRPH, High‐risk portal hypertension; PIIINP, Amino‐terminal propeptide of type III procollagen; TIMP‐1, Tissue inhibitor matrix metalloproteinase‐1