Abstract

The identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or in combination with other routine biochemical parameters. Subjects with overweight/obesity and ultrasound-confirmed liver steatosis (n = 112) from the Fatty Liver in Obesity (FLiO) study were assessed. The hepatic evaluation considered magnetic resonance imaging, ultrasonography, and credited routine blood liver biomarkers. Anthropometry and body composition, dietary intake (by means of a validated 137-item food frequency questionnaire), and specific biochemical markers were also determined. Serum ferritin levels were analyzed using a chemiluminescent microparticle immunoassay kit. Lower serum ferritin concentrations were associated with general better liver health and nutritional status. The evaluation of ferritin as a surrogate of liver damage by means of quantile regression analyses showed a positive association with alanine aminotransferase (ALT) (β = 19.21; p ≤ 0.001), liver fat content (β = 8.70; p = 0.008), and hepatic iron (β = 3.76; p ≤ 0.001), after adjusting for potential confounders. In receiver operating characteristic (ROC) analyses, the panel combination of blood ferritin, glucose, and ALT showed the best prediction for liver fat mass (area under the curve (AUC) 0.82). A combination of ferritin and ALT showed the higher predictive ability for estimating liver iron content (AUC 0.73). This investigation demonstrated the association of serum ferritin with liver health as well as with glucose and lipid metabolism markers in subjects with NAFLD. Current findings led to the identification of ferritin as a potential noninvasive predictive biomarker of NAFLD, whose surrogate value increased when combined with other routine biochemical measurements (glucose/ALT).

Highlights

  • Nonalcoholic fatty liver disease (NAFLD) is a condition defined by an excessive triglyceride accumulation in liver cells that is not caused by heavy alcohol consumption [1]

  • nonalcoholic fatty liver disease (NAFLD) is considered a multiorgan failure linked to obesity, cardiovascular disease (CVD), insulin resistance (IR), or metabolic syndrome (MetS) features [2,3,4]

  • The presence of hepatic steatosis was determined by ultrasonography, and hepatic fat was quantified by magnetic resonance imaging (MRI)

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Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a condition defined by an excessive triglyceride accumulation in liver cells that is not caused by heavy alcohol consumption [1]. NAFLD is considered a multiorgan failure linked to obesity, cardiovascular disease (CVD), insulin resistance (IR), or metabolic syndrome (MetS) features [2,3,4]. This morbid condition can lead to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and hepatocellular carcinoma [5]. The current reference standard, is an invasive and expensive procedure with some inherent surgical risks and only represents around 1/50,000 of the total hepatic volume [2,9]; it is still required for a definite diagnosis of NASH. Research is focusing on more efficient diagnostic and predictive biomarkers for identifying NAFLD features at early stages [2,9,10,11]

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