Investigating Molecular Connections of Non-alcoholic Fatty Liver Disease with Associated Pathological Conditions in West Virginia for Biomarker Analysis

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by a steatosis of the liver that may progress to more serious pathological conditions including: nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. As the prevalence of NAFLD has increased worldwide in recent years, pathophysiology and risk factors associated with disease progression of NAFLD are at the focus of many studies. NAFLD is related to and shares common serum biomarkers with cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome (MetS). West Virginia (WV) is a state with some of the highest rates of CVD, obesity and diabetes mellitus. As NAFLD is closely related to these diseases, it is of particular interest in WV. Currently there is no cost-effective, standardized method used clinically to detect NAFLD prior to the onset of reversible complications. At this time, the diagnosis of NAFLD is made with costly radiologic studies and invasive biopsy. These studies are only diagnostic once changes to hepatic tissue have occurred. The diagnosis of NAFLD by traditional methods may not allow for successful intervention and may not be readily available in areas with already sparse medical resources. In this literature review, we identify a list of biomarkers common among CVD, T2DM, obesity, MetS and NAFLD. From this research we propose the following biomarkers are good candidates for inclusion in a panel of biomarkers for the early detection of NAFLD: adiponectin, AST, ALT, apo-B, CK18, CPS1, CRP, FABP-1, ferritin, GGT, GRP78, HDL-C, IGF-1, IL-1β, 6, 8, 10, IRS-2PAI-1, leptin, lumican, MDA SREBP-1c and TNF-α. Creating and implementing a biomarker panel for the early detection and attenuation of NAFLD, prior to the onset of irreversible complication would provide maximum benefit and decrease the disease burden on the patients and healthcare system of WV.

Non-alcoholic fatty liver disease in the first trimester and subsequent development of gestational diabetes mellitus

“…In the current study, we examined the association between radiological and/or biochemical evidence of NAFLD in early pregnancy and the subsequent risk of developing GDM in pregnant Korean women. Moreover, since it is already known that adiponectin and selenoprotein P are likely to be responsible for linking hepatic steatosis to impaired glucose homeostasis [17,18], we investigated whether circulating levels of these cytokines are associated with NAFLD severity in pregnant women and can be used to predict the subsequent risk of developing GDM.…”

Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population

“…According to the 2018 West Virginia Behavioral Risk Factor Surveillance System Report, released by the West Virginia Department of Health and Human Resources, the prevalence of obesity and diabetes in West Virginia is around 37.7% (highest in the nation) and 15.0% (second highest nationally), respectively. The highest incidence of acute hepatitis B infection and acute hepatitis C infection in the US is also reported in West Virginia [4,5]. Studies have shown that hepatitis, in combination with obesity and insulin resistance, contributes to the disease progression of NAFLD in affected population [4,5].…”

“…The highest incidence of acute hepatitis B infection and acute hepatitis C infection in the US is also reported in West Virginia [4,5]. Studies have shown that hepatitis, in combination with obesity and insulin resistance, contributes to the disease progression of NAFLD in affected population [4,5].…”

Elucidating Potential Profibrotic Mechanisms of Emerging Biomarkers for Early Prognosis of Hepatic Fibrosis

“…These underlying pathologies of liver fibrosis are also associated with metabolic syndrome and its components, such as obesity, type II diabetes, and insulin resistance [ 15 , 17 , 18 ]. Therefore, early assessment of liver fibrosis in a population with a high prevalence of etiologies associated with advanced fibrosis, as mentioned earlier, is essential [ 19 , 20 , 21 ].…”