101. Demonstration of Gut-Barrier Dysfunction in Early Stages of Non-alcoholic Fatty Liver Disease: A Proof-Of-Concept Study
- Author
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Kanav Kaushal, Samagra Agarwal, Sanchit Sharma, Pooja Goswami, Namrata Singh, Vikas Sachdev, Shekhar Poudel, Prasenjit Das, Rajni Yadav, Dinesh Kumar, Gaurav Pandey, Deepak Gunjan, and Anoop Saraya
- Subjects
Hepatology ,Original Article - Abstract
BACKGROUND/AIMS: Gut-barrier dysfunction is well recognized in pathogenesis of both non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). However, comparison of components of this dysfunction between the two etiologies remains unexplored especially in early stages of NAFLD. METHODS: Components of gut-barrier dysfunction like alterations in intestinal permeability (IP) by lactulose mannitol ratio (LMR) in urine, systemic endotoxemia (IgG and IgM anti-endotoxin antibodies), systemic inflammation (serum tumor necrosis factor alpha [TNF-α] and interleukin-1 [IL-1] levels), tight junction (TJ) proteins expression in duodenal biopsy and stool microbiota composition using Oxford Nanopore MinION device were prospectively evaluated in patients with NAFLD (n = 34) with no cirrhosis, ALD (n = 28) and were compared with disease free controls (n = 20). RESULTS: Patients with ALD had more advanced disease than those with NAFLD (median liver stiffness -NAFLD:7.1 kPa [5.9–8.9] vs. ALD:14.3 kPa [9.6–24], P < 0.001]. Median LMR was significantly higher in NAFLD and ALD group when compared to controls (NAFLD 0.054 [0.037–0.17] vs. controls 0.027 [0.021–0.045] (P = 0.001)) and ALD 0.043 [0.03–0.068] vs. controls 0.027 [0.021–0.045] (P = 0.019)]. Anti-endotoxin antibody titer (IgM) (MMU/mL) was lowest in NAFLD 72.9 [3.2–1089.5] compared to ALD 120.6 [20.1–728]) (P = 0.042) and controls 155.3 [23.8–442.9]) (P = 0.021). Median TNF-α (pg/mL) levels were elevated in patients with NAFLD (53.3 [24.5–115]) compared to controls (16.1 [10.8–33.3]) (P < 0.001) and ALD (12.3 [10.1–42.7]) (P < 0.001). Expression of zonulin-1 and claudin-3 in duodenal mucosa was lowest in NAFLD. On principal co-ordinate analysis (PCoA), the global bacterial composition was significantly different across the three groups (PERMANOVA test, P < 0.001). CONCLUSION: While remaining activated in both etiologies, gut-barrier dysfunction abnormalities were more pronounced in NAFLD at early stages compared to ALD despite more advanced disease in the latter.
- Published
- 2022