Serum LPS and CD163 Biomarkers Confirming the Role of Gut Dysbiosis in Overweight Patients with NASH

BACKGROUND: Gut-microbiota alterations and bacterial translocation might attribute to hepatic inflammation. Lipopolysaccharide stimulates toll-like receptor 4 leading to the activation of Kupffer cells which express the surface receptor, CD 163. OBJECTIVE: To assess the levels of CD 163 and LPS in overweight and obese patients with different degrees of NAFLD as confirmed by liver biopsy (NAS score). METHODS: This is an observational case–control study. Sixty overweight and obese patients with NAFLD and 40 healthy controls were enrolled in the study. Liver biopsy was obtained from all participants with NAFLD. LPS and CD 163 levels were assessed using ELISA. RESULTS: The mean LPS and CD163 levels were significantly higher in patients with NAFLD when compared with healthy controls (p-value <0.001, p-value <0.001, respectively). LPS and CD163 levels were the lowest in Non-NASH (13.17 ± 3.34, 5.61 ± 2.35 ng/mL, respectively) and the highest in NASH (58.61 3± 3.81, 18.11 ± 6.84, respectively) (p-value <0.001, p-value <0.001, respectively). Statistically significant correlation was found between the levels of LPS and CD163 and NAS score (p-value <0.001, p-value < 0.001, respectively), steatosis grade (p-value <0.001, p-value <0.001, respectively), degree of inflammation (p-value 0.017, p-value <0.001, respectively) and ballooning (r= 0.663, p-value <0.001, r= 0.558, p-value <0.001, respectively). In ROC analysis, both sCD163 and LPS had high sensitivity and specificity in diagnosing NAFLD. CD163 and LPS had the high sensitivity and accuracy in discriminating NASH from Non-NASH (p-value <0.0001 in both). Moreover, the mean serum levels of LPS and sCD163 correlated positively and significantly with the BMI (r=0.329, p value<0.01; r=0.477. p value <0.001, respectively). CONCLUSION: sCD163 and LPS can be used as non-invasive tools for diagnosis and grading of NAFLD severity in overweight and obese patients, thus confirming the role of dysbiosis in fat deposition and inflammation and suggesting the potential benefits of gut-microbiota-targeted therapies in restoring the gut homeostasis.