Biomarkers of Hepatocellular Synthesis in Patients with Decompensated Cirrhosis

Overview

Journal Hepatol Int

Publisher Springer

Specialty Gastroenterology

Date 2023 Jan 18

PMID 36652164

Authors

Berivan Gurbuz

Nurdan Guldiken

Philipp Reuken

Lei Fu

Katharina Remih

Christian Preisinger

Radan Bruha

Martin Lenicek

Jaromir Petrtyl

Johanna Reissing

Mahmoud Aly

Malin Fromme

Biaohuan Zhou

Isabel Karkossa

Kristin Schubert

Martin von Bergen

Andreas Stallmach

Tony Bruns

Pavel Strnad

Affiliations

Soon will be listed here.

Abstract

Background And Aim: Since hepatocytes produce majority of serum proteins, patients with cirrhosis display substantial alterations in the serum proteome. The aim of the current study was to characterize these changes and to study the prognostic utility of hepatocellular proteins available in routine clinical testing.

Methods: Sera from 29 healthy controls and 43 patients with cirrhosis were subjected to untargeted proteomic analysis. Unsupervised hierarchical clustering was performed with Perseus software and R. Ingenuity pathway analysis (IPA) suggested upstream regulators that were validated in liver tissues. The behavior and prognostic usefulness of selected biomarkers was investigated in 61 controls and 285 subjects with decompensated cirrhosis.

Results: Proteomics uncovered 65 and 16 hepatocellular serum proteins that are significantly downregulated or upregulated in patients with cirrhosis vs. controls. Hierarchical clustering revealed two main clusters and six sub-clusters. IPA identified HNF4α and IL-6 as the two major upstream regulators that were confirmed by hepatic gene expression analyses. Among pseudocholinesterase, transferrin, transthyretin, albumin, and apolipoprotein AI (Apo-AI), Apo-AI was the best predictor of 90-days transplant-free survival (AUROC 0.678; p = 0.0001) and remained an independent predictor in multivariable Cox independently of the presence of acute-on-chronic liver failure.

Conclusion: Our study reveals cirrhosis-associated changes in hepatocellular serum proteins and underlying transcription factors. Serum apolipoprotein AI may constitute a useful prognostic adjunct in patients with decompensated cirrhosis.

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