Association of Serum Cytokines with Liver Fibrosis as Measured by Computerized Morphometry across Diseases of NAFLD Spectrum

Abstract

Global prevalence of nonalcoholic fatty liver disease (NAFLD) is currently at 25%, and is expected to increase as a major public health concern due to the current worldwide obesity epidemic. The spectrum of NAFLD includes nonalcoholic steatohepatitis (NASH) and steatohepatitis-related hepatocellular carcinoma (SH-HCC). Not all patients with NAFLD progress to NASH. Molecular mechanisms behind the development and progression of this disease are poorly understood. The diagnosis and grading of NAFLD/NASH is dependent on the “gold standard” of invasive liver biopsy. This study attempts to correlate levels of serum biomarkers with quantified fibrotic changes in liver tissue biopsies of NAFLD patients. Liver biopsies from obese non-NAFLD, NAFLD, and NASH patients were analyzed via computerized morphometry to quantify the extent of steatosis and fibrosis. Results of immunoassaying of serum samples collected from histologically assessed patients indicate a negative correlation of the levels of IL-7 (p<0.05), IL-10 (p<0.01), G-CSF (p<0.05), and GM-CSF (p<0.05) with the extent of collagen deposits in liver biopsies. Nevertheless, when the levels of these cytokines were compared across the diseases of NAFLD spectrum, no significant differences in these levels were detected. We conclude that the levels of serum cytokines reflect amounts of the fibrosis in liver parenchyma assessed by computerized morphometry with better precision that standard histology-based categorization of NAFLD patients into diagnostic subgroups. Serum cytokine levels have a potential to be developed into sensitive diagnostic and/or prognostic biomarkers for non-invasive assessment and long-term monitoring of NAFLD.