Hepatic and Systemic Effect of Non-Alcoholic Fatty Liver Disease Severity in Obese and Non-Obese Indian Patients

Background: Non-alcoholic fatty liver disease (NAFLD) is now predominant globally due to increased sedentary lifestyle and obesity. Recently, high prevalence of NAFLD also has been documented in non-obese individuals with increased risk of cirrhosis and hepatocellular carcinoma. The systemic and hepatic manifestations of NAFLD severity in obese and non-obese Indian patients are not clear. Methods: The clinically diagnosed NAFLD patients (n=54, non-obese and obese) were assessed for liver injury and hepatic fat content by histopathology, Fibroscan and MRS. Liver biopsy and hepatic venous sampling were performed by trans-jugular approach and mRNA expression was assessed by real-time PCR. Result: High liver fat content (LFC, 20. 4 ± 10. 4%, 16 ± 11. 5% and 9. 34 ± 15. 4%) and increased abdominal obesity (WHR, 1. 03 ± 0. 06, 0. 97 ± 0. 05 and 0. 93 ± 0. 06) was observed in both obese and non-obese NAFLD patients as compare to disease control. Histopathological examination of liver indicated increased fibrosis (grade ≥ 1) in both obese (76%) and non-obese (64%) group. Significant increased levels of LBP, MDA and adipokines levels (p < 0. 001) were observed in hepatic and systemic circulation of obese and non-obese groups than healthy and diseased controls. A positive correlation of biomarkers for liver injury was found between hepatic and systemic circulation. Hepatic gene expression of adipokines and cytokines also corroborated this trend among groups. Conclusion: The extent of liver injury is quite high in both non-obese and obese NAFLD patients. The drivers of injury in these patients are due to hepatic fat and SIBO induced endotoxin mediated up-regulation of proinflammatory adipocytokines and oxidant stress in liver