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=8

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=<p><bold>Background:</bold> Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome.</p><p><bold>Materials and Methods:</bold> Leptin, adiponectin, and 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.</p><p><bold>Results:</bold> In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; <italic>p</italic> &lt; 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; <italic>p</italic> &lt; 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; <italic>p</italic> &lt; 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; <italic>p</italic> &lt; 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, <italic>p</italic> &lt; 0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; <italic>p</italic> &lt; 0.01).</p><p><bold>Conclusion:</bold> Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis.</p>