Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1007/s12072-022-10473-x
Licence creative commons licence
Title (Primary) Biomarkers of hepatocellular synthesis in patients with decompensated cirrhosis
Author Gurbuz, B.; Guldiken, N.; Reuken, P.; Fu, L.; Remih, K.; Preisinger, C.; Brůha, R.; Leníček, M.; Petrtýl, J.; Reissing, J.; Aly, M.; Fromme, M.; Zhou, B.; Karkossa, I.; Schubert, K.; von Bergen, M.; Stallmach, A.; Bruns, T.; Strnad, P.
Source Titel Hepatology International
Year 2023
Department iDiv; MOLSYB
Volume 17
Issue 3
Page From 698
Page To 708
Language englisch
Topic T9 Healthy Planet
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Keywords Mass spectrometry; Fibrosis; Interleukin; Hepatocyte nuclear factor; Decompensated cirrhosis
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.

Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=24604
Gurbuz, B., Guldiken, N., Reuken, P., Fu, L., Remih, K., Preisinger, C., Brůha, R., Leníček, M., Petrtýl, J., Reissing, J., Aly, M., Fromme, M., Zhou, B., Karkossa, I., Schubert, K., von Bergen, M., Stallmach, A., Bruns, T., Strnad, P. (2023):
Biomarkers of hepatocellular synthesis in patients with decompensated cirrhosis
Hepatol. Int. 17 (3), 698 - 708