Abstract
Fibrosis is the strongest predictor for disease-specific mortality in non-alcoholic fatty liver diseases (NAFLD), but the need for liver biopsy limits its diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis identified by an in silico discovery strategy. Two hundred and thirty-five morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n = 44; F1, n = 134; F2, n = 46; F3/F4, n = 11) and 40 cirrhotic patients were enrolled. The cohort was subdivided into discovery (n = 76) and validation groups (n = 159). The plasma level of FCN-2 and other candidate markers was determined. FCN-2 was inversely correlated with the stage of liver fibrosis (ρ = −0.49, p < 0.001) independently of steatosis (p = 0.90), inflammation (p = 0.57), and ballooning (p = 0.59). In the global cohort, FCN-2 level decreased significantly in a stepwise fashion from F0/F1 (median 4753 ng/mL) to F2–F3–F4 (2760 ng/mL) and in cirrhotic subjects (1418 ng/mL). The diagnostic performance of FCN-2 in detecting F ≥ 2 was higher than other indexes (APRI, FIB-4) (AUROC 0.82, 0.68, and 0.6, respectively). The accuracy improved when combined with APRI score and HDL values (FCNscore, AUROC 0.85). Overall, the FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs. moderate/advanced) significantly improving the fibrosis diagnostic algorithms.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide and is expected to become the leading cause of liver transplantation by 2030 [1,2]
Two pathways have been exploited in approaching alternatives to the gold standard: blood-based non-invasive indirect tests have been combined in indices such as the fibrosis-4 (FIB-4) score [7], the AST to platelet ratio index (APRI), or individual markers in indirect tests such as the type III collagen neo-epitopes (PRO-C3) [8]
By using the described strategy, we identified some proteins as candidate biomarkers for liver fibrosis
Summary
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide and is expected to become the leading cause of liver transplantation by 2030 [1,2]. Metabolic disorders such as type 2 diabetes mellitus (T2DM) and obesity increase the risk of developing severe liver disease in NAFLD [3]. Two pathways have been exploited in approaching alternatives to the gold standard: blood-based non-invasive indirect tests have been combined in indices such as the fibrosis-4 (FIB-4) score [7], the AST to platelet ratio index (APRI), or individual markers in indirect tests such as the type III collagen neo-epitopes (PRO-C3) [8]
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