AUTHOR=Marques Vanda , Afonso Marta B. , Bierig Nina , Duarte-Ramos Filipa , Santos-Laso Álvaro , Jimenez-Agüero Raul , Eizaguirre Emma , Bujanda Luis , Pareja Maria J. , Luís Rita , Costa Adília , Machado Mariana V. , Alonso Cristina , Arretxe Enara , Alustiza José M. , Krawczyk Marcin , Lammert Frank , Tiniakos Dina G. , Flehmig Bertram , Cortez-Pinto Helena , Banales Jesus M. , Castro Rui E. , Normann Andrea , Rodrigues Cecília M. P. 

TITLE=Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD

JOURNAL=Frontiers in Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.683250

DOI=10.3389/fmed.2021.683250

ISSN=2296-858X

ABSTRACT=Objective: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains gold-standard for diagnosis. Here, we evaluated circulating metabolism-related hormones as non-invasive NAFLD biomarkers, and their correlation with the metabolome. 
Materials and Methods: Leptin, adiponectin and insulin-like growth factor 1 (IGF-1) serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls), and correlated with clinical data, histology, genetic parameters and serum metabolomics. 
Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 0.0001). Leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In discovery cohort, adiponectin was lower in nonalcoholic steatohepatitis (NASH) vs. nonalcoholic fatty liver (AUROC 0.87; p < 0.0001). For validation cohort significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p < 0.05). Combining adiponectin with specific serum lipids improved assay performance (AUROC 0.80; p < 0.0001). For validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p < 0.05), but combination with international normalized ratio (INR) and ferritin increased assay performance (AUROC 0.81; p < 0.01). 
Conclusion: Serum leptin discriminates NAFLD and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR and ferritin distinguish advanced fibrosis.