Proteomic screening of plasma identifies potential noninvasive biomarkers associated with significant/advanced fibrosis in patients with nonalcoholic fatty liver disease.

Wei Hou,Philip M Sobolesky,Wing-Kin Syn,Alison M Bland,Michael G Janech,Salma Samsuddin,William Alazawi

doi:10.1042/bsr20190395

Abstract

Noninvasive biomarkers are clinically useful for evaluating liver fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to compare plasma proteins in patients with early nonalcoholic steatohepatitis (NASH) (F0-F1) versus NASH with significant/advanced fibrosis (F2–F4) to determine whether candidate proteins could be used as potential noninvasive biomarkers. Nineteen biopsy-proven NAFLD patients including ten early NASH patients and nine NASH patients with significant/advanced fibrosis were enrolled in the present study. High-resolution proteomics screening of plasma was performed with the SCIEX TripleTOF 5600 System. Proteins were quantified using two different software platforms, Progenesis Qi and Scaffold Q+, respectively. Progenesis Qi analysis resulted in the discovery of 277 proteins compared with 235 proteins in Scaffold Q+. Five consensus proteins (i.e. Complement component C7; α-2-macroglobulin; Complement component C8 γ chain; Fibulin-1; α-1-antichymotrypsin) were identified. Complement component C7 was three-fold higher in the NASH group with significant/advanced fibrosis (F2–F4) compared with the early NASH (F0-F1) group (q-value = 3.6E-6). Complement component C7 and Fibulin-1 are positively correlated with liver stiffness (P=0.000, P=0.002, respectively); whereas, Complement component C8 γ chain is negatively correlated (P=0.009). High levels of Complement C7 are associated with NASH with significant/advanced fibrosis and Complement C7 is a perfect classifier of patients included in this pilot study. Further studies will be needed in a larger validation cohort to confirm the utility of complement proteins as biomarkers or mechanistic determinants of NASH with significant/advanced fibrosis.

Highlights

Nonalcoholic fatty liver disease (NAFLD), one of the most common liver diseases worldwide, can be categorized histologically into nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH) [1]
A total of 19 biopsy-proven NAFLD patients were enrolled in the present study, including 10 early NASH patients and 9 NASH patients with significant/advanced fibrosis
The present study showed for the first time that Complement component 7 (C7) and C8 γ chain and Fibulin-1 significantly correlate with liver stiffness

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD), one of the most common liver diseases worldwide, can be categorized histologically into nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH) [1]. Evaluating liver fibrosis stage in NAFLD patients is of importance for identifying those who may progress to liver cirrhosis and hepatocellular carcinoma. A liver biopsy is the gold standard for diagnosing and determining the stages of fibrosis, there is an urgent need to develop noninvasive. The purpose of the present study was to perform proteomic screening of plasma via SCIEX TripleTOF 5600 System [33,34,35] to identify potential noninvasive biomarkers in NAFLD patients with significant/advanced liver fibrosis Methods [2,3,4,5,6,7,8,9,10,11,12], including imaging modalities [13,14,15,16,17], biomarkers [18,19,20,21,22,23,24,25,26], and artificial intelligence algorithms [27,28,29,30,31,32].

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Conclusion