Dipeptidyl peptidase-3 is associated with severity of liver disease and circulatory complications in patients with cirrhosis

Abstract

Background

Patients with cirrhosis suffer from a complex multiorgan disturbance and their prognosis is influenced by the development of portal hypertension and systemic circulatory dysfunction. Although non-invasive techniques such as transient elastography aid in early detection, there is an unmet need for reliable markers of these clinically significant complications.

Methods

We conducted an exploratory single-center study investigating dipeptidyl peptidase-3 (DPP3) concentrations in various vascular beds in a cohort of 48 patients with cirrhosis and 16 healthy controls. Liver vein catheterisation with sampling from femoral artery and femoral, renal and hepatic veins as well as measurement of hepatic pressure and liver function via indocyanine green and galactose elimination tests were performed.

Results

DPP3 concentrations were higher in cirrhotic patients compared to controls (12.6 vs. 7.4 ng/mL, p = 0.006) and increased according to the severity of cirrhosis. DPP3 associated with MELD-Na score, Child class, indocyanine green clearance, increased DPP3 with the increased hepatic venous pressure gradient (p = 0.015) as well as increased heart rate and reduced systemic vascular resistance. DPP3 concentrations predicted the presence of clinically significant portal hypertension in cirrhotic patients (AUROC 0.78, 95% CI 0.65–0.9).

Conclusion

DPP3 is a promising marker for portal hypertension and systemic hemodynamic changes in cirrhosis.

Keywords:

• Dipeptidyl peptidase-3
• cirrhosis
• portal hypertension
• biomarkers
• hemodynamics

Ethical approval

Approved by the local ethics Committee for Medical Research in Copenhagen (H-18048245) and Danish Data Protection Agency (J-No.2008-41-2020) and registered Pathophysiological Bio bank at Hvidovre Hospital (HVH-2011-02).

Author contributions

Andrei Voiosu and Søren Møller conceived and designed the study. Andrei Voiosu provided initial statistical analysis and wrote the first draft. Signe Wiese collected the data and contributed statistical input. Jens P Goetze, Oliver Hartmann, Theodor Voiosu and Karine Santos checked the statistical analysis, contributed analysis tools and references and participated in the rewriting of the subsequent drafts. All authors contributed significantly, reviewed, corrected and approved the final draft

Disclosure statement

In accordance with Taylor & Francis policy and my ethical obligation as a researcher, I am reporting that Drs. Oliver Hartmann and Karine Santos Bourgeois are affiliated to Sphingotec GmbH, the commercial manufacturer of the DPP3 methodology and 4TEEN4 Pharmaceuticals, which holds patents to the DPP3 biomarker. All other authors have no conflicts of interest to declare.

Data availability statement

The data that support the findings of this study are available from the corresponding author, AV, upon reasonable request.