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Abstract
(1) Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the presence of fatty liver, hepatic inflammation and fibrogenesis eventually leading to nonalcoholic steatohepatitis (NASH) or cirrhosis. Obesity and diabetes are common risk factors associated with the development and progression of NAFLD, with one of the highest prevalence of these diseased conditions in the West Virginia population. Currently, the diagnosis of NAFLD is limited to radiologic studies and biopsies, which are not cost-effective and highly invasive. Hence, this study aimed to develop a panel and assess the progressive levels of circulatory biomarkers and miRNA expression in patients at risk for progression to NASH to allow early intervention strategies. (2) Methods: In total, 62 female patients were enrolled and blood samples were collected after 8–10 h of fasting. Computed tomography was performed on abdomen/pelvis following IV contrast administration. The patients were divided into the following groups: Healthy subjects with normal BMI and normal fasting blood glucose (Control, n = 20), Obese with high BMI and normal fasting blood glucose (Obese, n = 20) and Obese with high fasting blood glucose (Obese + DM, n = 22). Based on findings from CT, another subset was created from Obese + DM group with patients who showed signs of fatty liver infiltration (Obese + DM(FI), n = 10). ELISA was performed for measurement of plasma biomarkers and RT-PCR was performed for circulating miRNA expression. (3) Results: Our results show significantly increased levels of plasma IL-6, Leptin and FABP-1, while significantly decreased level of adiponectin in Obese, Obese + DM and Obese + DM(FI) group, as compared to healthy controls. The level of CK-18 was significantly increased in Obese + DM(FI) group as compared to control. Subsequently, the expression of miR-122, miR-34a, miR-375, miR-16 and miR-21 was significantly increased in Obese + DM and Obese + DM(FI) group as compared to healthy control. Our results also show distinct correlation of IL-6, FABP-1 and adiponectin levels with the expression of miRNAs in relation to the extent of NAFLD progression. (4) Conclusion: Our results support the clinical application of these biomarkers and miRNAs in monitoring the progression of NAFLD, suggesting a more advanced diagnostic potential of this panel than conventional methods. This panel may provide an appropriate method for early prognosis and management of NAFLD and subsequent adverse hepatic pathophysiology, potentially reducing the disease burden on the West Virginia population.
Highlights
(3) Results: Our results show significantly increased levels of plasma IL-6, Leptin and Fatty acid-binding proteins (FABPs)-1, while significantly decreased level of adiponectin in Obese, Obese + DM and Obese + DM(FI) group, as compared to healthy controls
Our results show distinct correlation of IL-6, fatty acid binding protein 1 (FABP-1) and adiponectin levels with the expression of miRNAs in relation to the extent of Nonalcoholic fatty liver disease (NAFLD) progression
Nonalcoholic fatty liver disease (NAFLD) is a heterogenous spectrum of diseases progressing from simple steatosis to nonalcoholic steatohepatitis (NASH) with/without fibrosis, cirrhosis and hepatocellular carcinoma (HCC), occurring in a dysmetabolic milieu [1,2]
Summary
Nonalcoholic fatty liver disease (NAFLD) is a heterogenous spectrum of diseases progressing from simple steatosis to nonalcoholic steatohepatitis (NASH) with/without fibrosis, cirrhosis and hepatocellular carcinoma (HCC), occurring in a dysmetabolic milieu [1,2]. It is rapidly becoming a major global health problem due to marked lifestyle changes, especially in western countries, with the rising prevalence closely mirroring the epidemic of obesity and Type II Diabetes Mellitus (T2DM). Studies have shown that hepatitis, in combination with obesity and insulin resistance, contributes to the disease progression of NAFLD in affected population [4,5]
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