Liver, Pancreas and Biliary Tract
Placental growth factor levels neither reflect severity of portal hypertension nor portal-hypertensive gastropathy in patients with advanced chronic liver disease

https://doi.org/10.1016/j.dld.2020.09.006Get rights and content
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Abstract

Background & Aims

Experimental data indicates that placental growth factor (PLGF) is involved in the pathophysiology of portal hypertension (PH) due to advanced chronic liver disease (ACLD). We investigated serum levels of PLGF and its “scavenger”, the receptor soluble fms-like tyrosine kinase-1 (sFLT1, or sVEGFR1), in ACLD patients with different severity of PH and portal-hypertensive gastropathy (PHG).

Methods

PLGF and sVEGFR1 were measured in ACLD patients with hepatic venous pressure gradient (HVPG) ≥6 mmHg (n = 241) and endoscopic evaluation of PHG (n = 216). Patients with pre-/posthepatic PH, TIPS, liver transplantation and hepatocellular carcinoma were excluded.

Results

Thirty-two (13%) patients had HVPG 6–9 mmHg, 128 (53%) 10–19 mmHg and 81 (34%) ≥20 mmHg; 141 (59%) had decompensated ACLD (dACLD). PLGF (median 17.2 vs. 20.8 vs. 22.4 pg/mL; p = 0.002), sVEGFR1 (median 96.0 vs. 104.8 vs. 119.3 pg/mL; p < 0.001) levels increased across HVPG strata, while PLGF/sVEGFR1 ratios remained similar (0.19 vs. 0.20 vs. 0.18 pg/mL; p = 0.140). The correlation between PLGF and HVPG was weak (Rho = 0.190,95%CI 0.06–0.31; p = 0.003), and the PLGF/sVEGFR1 ratio did not correlate with HVPG (p = 0.331). The area-under-the-receiver operating characteristics (AUROC) for PLGF to detect clinically significant PH (CSPH;i.e. HVPG ≥ 10 mmHg) yielded only 0.688 (0.60–0.78; p < 0.001).

When compared to ACLD patients without PHG, PLGF levels (20 without vs. 21.4 with mild vs. 17.1 pg/mL with severe PHG, respectively; p = 0.005) and PLGF/sVEGFR1 ratios (0.20 vs. 0.19 vs. 0.17; p = 0.076) did not increase with mild and severe PHG.

Conclusion

While PLGF levels tended to increase with severity of PH, the PLGF/sVEGFR1 ratio remained stable across HVPG strata. Neither PLGF nor the PLGF/sVEGFR1 ratio had diagnostic value for prediction of CSPH. The severity of PHG was also not associated with stepwise increases in PLGF levels or PLGF/sVEGFR1 ratio.

Keywords

Cirrhosis
HVPG
PLGF
SFLT1
Angiogenesis
Portal-hypertensive gastropathy

Abbreviations

PLGF
placental growth factor
PH
portal hypertension
ACLD
advanced chronic liver disease
SFLT1/svegfr1
soluble FMS-like tyrosine kinase-1/soluble vascular endothelial growth factor receptor-1
HVPG
hepatic venous pressure gradient
PHG
portal-hypertensive gastropathy
c/dACLD
compensated/decompensated acld
AUROC
area-under-the-receiver operating characteristics
CSPH
clinically significant portal hypertension
VEGF
vascular endothelial growth factor
PPVL
partial portal vein ligation
CCl4
carbon tetrachloride
ALD
alcohol-related liver disease
HCC
hepatocellular carcinoma
TIPS
transjugular intrahepatic portosystemic shunt
NSBB
non-selective betablocker
SEM
standard error of the mean
IQR
interquartile range
CTP
Child-Turcotte-Pugh
MELD-Na
model for end-stage liver disease including sodium
HE
hepatic encephalopathy
PLT
platelets
HCV
hepatitis C

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1

BeSi and AS contributed equally to this manuscript.