Heightened Plasma Levels of Transforming Growth Factor Beta (TGF-β) and Increased Degree of Systemic Biochemical Perturbation Characterizes Hepatic Steatosis in Overweight Pediatric Patients: A Cross-Sectional Study.

Junaura R Barretto,Monica A S Torres-Nascimento,Ney Boa-Sorte,Camila F Ramos,Jessica Rebouças-Silva,Hayna Malta-Santos,Bruno B Andrade,Caian L Vinhaes,Valeria M Borges

doi:10.3390/nu12061650

Abstract

Nonalcoholic Fatty Liver Disease (NAFLD) is a common cause of chronic liver disease in childhood and strongly associated with obesity. Routine biochemical non-invasive tests remain with low accuracy for diagnosis of NAFLD. We performed a cross-sectional study to examine potential associations between anthropometric and biochemical parameters, specially TGF-β, a prognosis marker for hepatic steatosis (HS). Between May and October 2019, seventy-two overweight adolescents were enrolled, of which 36 had hepatic steatosis. Hepatic, lipidic and glycemic profiles, and levels of vitamin D, ferritin and TGF-β were analyzed. Hierarchical cluster and a discriminant model using canonical correlations were employed to depict the overall expression profile of biochemical markers and the biochemical degree of perturbation. Median values of alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), and TGF-β were higher in the adolescents with HS. Values of body mass index (BMI)/age and ALT, but not of TGF-β, were gradually increased proportionally to augmentation of steatosis severity. In a multivariate analysis, TGF-β plasma concentrations were associated with occurrence of hepatic steatosis independent of other covariates. Discriminant analysis confirmed that TGF-β concentrations can identify HS cases. Our data reveal that HS patients exhibit a distinct biosignature of biochemical parameters and imply TGF-β as an important biomarker to evaluate risk of steatosis development.

Highlights

Non-alcoholic fatty liver disease (NAFLD) represents a generic term that includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), and the evolution to fibrosis or cirrhosis [1,2]
We found that the patients with hepatic steatosis could be distinguished from those without steatosis with high degree of accuracy (area under the curve (AUC) of the receiver operator characteristics (ROC) curve = 0.97 (CI: 0.85–1.0), sensitivity 91% (CI: 77.0–96.7), specificity
These results argue correlations) that hepatic steatosis is associated with alterations in relevant to explain the differences between the study groups described in the discriminant the profile of correlations between values of the biochemical parameters evaluated here

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) represents a generic term that includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), and the evolution to fibrosis or cirrhosis [1,2]. Such a condition develops in the absence of secondary causes, such as medications or metabolic diseases [1,2]. A higher prevalence of childhood obesity and its associated comorbidities, especially metabolic syndrome and dyslipidemia, is followed by increases in the prevalence and severity of NAFLD [1,4,5,8,9,10]. Severe obesity is associated with more adverse clinical outcomes and greater risk of progression to NASH and cirrhosis in childhood [11,12]

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Conclusion