Abstract
Background: 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.Materials and Methods: 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.Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 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; p < 0.0001). For the 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 the assay performance (AUROC 0.80; p < 0.0001). For the 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 the 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.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver conditions and an important risk factor for liver cirrhosis and hepatocellular carcinoma
The non-alcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) patients were similar with respecting to age, gender, body mass index (BMI), gamma-glutamyl transferase (GGT), serum glucose, triglycerides, and cholesterol [total, highdensity lipoprotein (HDL) or low-density lipoprotein (LDL)] concentrations (Tables 1, 2)
Liver fat content evaluated by magnetic resonance imaging and Folch method were increased in NASH vs. NAFL (p < 0.05)
Summary
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver conditions and an important risk factor for liver cirrhosis and hepatocellular carcinoma. The NAFLD spectrum varies from simple fat accumulation to nonalcoholic steatohepatitis (NASH), characterized by hepatocellular injury, inflammation, and, eventually, fibrosis [1]. Clinical practice guidelines recommend NAFLD screening in individuals with metabolic risk factors, such as obesity, type 2 diabetes, and hypertension (metabolic syndrome) [3, 4]. Differential diagnosis between non-alcoholic fatty liver (NAFL) and NASH is an important indicator of increased risk of cirrhosis and other hepatic co-morbidities, the stage of fibrosis is increasingly recognized as the most relevant NASH prognostic marker [5]. 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
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