engleski

Identification of new candidate biomarkers for clinicall y significant portal hypertension by serum proteomic profiling of patients with compensated advanced chronic liver disease

Introduction and objective. Complications of portal hypertension begin to develop at hepatic vein pressure gradient (HVPG) ≥10 mm Hg (considered as clinically significant portal hypertension, CSPH), hence early identification of patients with CSPH is of high importance. HVPG is an invasive procedure, with limited availability, thus noninvasive tests represent an attractive diagnostic alternative. In this study, we aimed to identify the potential new serum biomarkers for CSPH in patients with compensated advanced chronic liver disease (cACLD) by serum proteomic profiling. Methods. The presence of CSPH in patients with cACLD and no history of liver decompensation was assessed by HVPG measurement. Serum samples were pooled based on HVPG result into groups without (HVPG <10 mm Hg, n=18) and with CSPH (HVPG ≥10 mm Hg, n=30). Serum pools were purified using HiTrap heparin sepharose columns and analyzed by liquid chromatography-mass spectrometry. Samples were analyzed in triplicates and proteins identified with at least one peptide were considered relevant for analysis. Functional enrichment analysis was conducted using FunRich 3.1.3 analysis tool. Results. A total of 48 patients were included (75% males ; median age: 59.9±9.8 years ; the majority with alcoholic (48%) and non-alcoholic (23%) fatty liver disease. A total of 357 proteins were identified in CSPH and 359 in no-CSPH group, and were classified into several functional subsets. Serum level of proteins involved in platelet degranulation, lipid transport and vasodilatation were more represented, those involved in immune response were less represented in the CSPH group, whereas proteins involved in extracellular matrix (ECM) regulation were equally represented in both groups. The proteins with the most striking difference between the groups were metalloproteinase inhibitor 2 (involved in the ECM regulation) and protein S100-A8 (involved in the inflammatory and immune response), both with 11- fold higher concentration in the CSPH group. Other proteins with >2x higher concentrations in the CSPH group were fibulin-1, mannose-binding protein C, macrophage colony-stimulating factor 1 receptor, plexin domain-containing protein 2, and phosphatidylcholine-sterol acyltransferase. Conclusion. We identified candidate serum biomarkers for early recognition of CSPH in patients with cACLD. These proteins are likely involved in the pathophysiology of portal hypertension development and might represent potential therapeutic targets, which warrants further investigation.

portal hipertension ; serum biomarkers ; proteomic profiling ; chronic liver disease

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