The Differential Gene Expression Analysis Of Hepatic Inflammatory Genes For Diagnosis Of Early Stages Of Fibrosis In Non Alcoholic Fatty Liver Disease (NAFLD)

Abstract

Nonalcoholic Fatty Liver Disease (NAFLD) is the common liver metabolic disorders, which affects more than 30% of the world’s population. If NAFLD is left untreated, it progresses to advance stages such non-alcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Inflammation being an initiator in the progression of NAFLD to advance stages The fundamental purpose of this study was to diagnose the progressive stages of NAFLD by quantitative gene expression of inflammatory biomarkers including IL-6, TNF-α and IL-2R-α on biopsy-proven NAFLD patients as well as based on recommended fibroscan in three groups i.e. No fibrosis, early stages of fibrosis; F1 & F2 and late fibrosis; F3. Liver biopsy is the gold standard for quantifying steatosis, NASH and fibrosis in liver.  However, it is an invasive procedure with potential adverse effects and large inter observer variability. Fibroscan is also being used to categorize fibrosis stages, however, it overestimates the fibrosis score in the early stages of fibrosis (F1 & F2) in NAFLD. Hence, various noninvasive markers are need for the diagnosis of early stages of liver fibrosis (F1 & F2). The liver tissue biopsies and blood samples were collected as per defined criteria i.e. deranged Liver Function Tests (LFTs) as well as recommended fibroscan scores.  Our results showed that tshe ALT/AST ratio was increased in early (1.17) and late fibrosis (1.41) and the mean fibroscan scores observed for early fibrosis (F1 & F2) and late fibrosis (F3) were 8.64 Median kPA and 12.02 Median kPA respectively. The quantitative differential expression of all three hepatic inflammatory biomarkers including IL-6, TNF-α and IL-2R-α on biopsy-proven NAFLD patients showed significant upregulation in both early and late fibrosis The highest significant quantitative changes in gene expression such as 4.79-fold and 16.45-fold were observed in the case of IL-6 in early and late fibrosis NAFLD patients respectively in comparison to other two inflammatory biomarkers (TNF-α, IL-2R-α). Therefore, the data of this study suggest that the quantitate expression analysis of these three inflammatory genes may be used as biomarkers for noninvasive tests for early dignosis and progression of advance stages of fibrosis in NAFLD patients.