Background & Aims: In the next 20 years, non-alcoholic fatty liver disease (NAFLD) is expected to become the leading cause of liver transplantation. Fibrosis is the most important prognostic factor for liver-related outcomes and mortality, but the need for liver biopsy limits diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis. FCN-2 candidate was selected by an in silico discovery strategy.
Methods: We enrolled 235 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 as positive controls. The cohort was subdivided into discovery (n=76) and validation groups (n=159). The plasma level of FCN-2 and other biomarkers was determined by enzyme-linked immunoabsorbent assay.
Results: Plasma level of FCN-2 correlated inversely with the stage of liver fibrosis (ρ = -0.49, p<0.0001), 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 fibrosis was higher than that of other fibrosis indexes (APRI, FIB-4, NFS) (AUROC 0.82, 0.68, 0.67, and 0.68, respectively), sh o wing a substantially improved accuracy when combined with APRI score and HDL plasma values in a diagnostic index (FCNscore, AUROC 0.85).
Conclusion: FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs . moderate/advanced). Its inclusion in the diagnostic workup significantly improves the fibrosis diagnostic algorithms.