Acute variceal bleed in cirrhosis is associated with reversible changes in tight junction protein expression in the intestine. A proof-of-concept study

Abstract Background Tight junction proteins(TJPs) play an important role in gut-barrier dysfunction in cirrhosis, and its complications like acute variceal bleed(AVB). However, the dynamics of TJPs expression post AVB, its relation to bacterial translocation, and impact on clinical outcome is largely unknown. Aims To study the expression of TJPs in cirrhosis and assess its dynamic changes in AVB. Also, the relation of TJPs expression to endotoxemia and clinical outcomes was assessed. Methods In this prospective pilot study, 17 patients of cirrhosis with AVB, 59 patients of cirrhosis without AVB(non-AVB cirrhosis), and 20 controls were assessed for claudin-2 and claudin-4 expression in the duodenal biopsy. In the AVB-cirrhosis group, additional biopsies were obtained after 3 weeks. Endotoxemia was assessed by measuring IgG anti-endotoxin antibody levels. Claudin expression was correlated with 6-month survival. Results Claudin-2 expression was downregulated in patients with AVB and non-AVB cirrhosis in villi (p Conclusion Both claudin-2 and claudin-4 expression are downregulated in cirrhosis. AVB is associated with dynamic changes in TJPs expression. Gut-barrier dysfunction might predict outcomes independent of bacterial endotoxemia in cirrhosis.