Abstract
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.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is predominant globally due to increased sedentary lifestyle and obesity
The hepatic venous blood sampling was performed in NAFLD patients and chronic hepatitis B (CHB) controls through trans-jugular approach [19]
The present study provided specific clinical patterns of NAFLD associated with WHO criteria of obesity and without so, and identified the limitations of established criteria of screening individuals for NAFLD in Indians
Summary
All consecutive NAFLD patients and chronic hepatitis B (CHB) as disease control attending liver clinics were recruited as per inclusion and exclusion criteria. The CHB patients with minimum 1.5 times elevated ALT and without any evidence of fatty liver on histology, were included as disease controls. Healthy individuals matched for age, sex and BMI with normal liver function tests and without any evidence of fatty liver (on USG), diabetes mellitus or alcohol consumption or any other comorbid diseases, were included as healthy controls. The hepatic venous blood sampling was performed in NAFLD patients and CHB controls through trans-jugular approach [19]. The relative expression of LBP, proinflammatory cytokine and adipokine genes in liver of non-obese and obese NAFLD patients as compared to CHB disease control were analyzed by comparative Ct method using GAPDH gene as endogenous normalization control. Associations between variables were performed using Spearman’s correlation coefficients
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