P094 Potential mechanisms underlying the protective effect of long-term albumin infusion in cirrhosis

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<h3>Background</h3> Long-term albumin administration has shown a reduction in mortality in hepatic decompensation, however the mechanism of this is unclear. The aims of this study were to determine (i) whether analbuminaemic (NAR) rats have greater liver injury and sensitivity to LPS (ii) whether albumin infusion is protective in NAR rats (iii) the impact of analbuminaemia and albumin infusion on the gut-liver interface and hepatic TLR4 signalling. <h3>Methods</h3> 10 treatment groups of NAR and SD rats were studied (n=4–7); Naïve, cirrhosis (4-w after bile duct ligation (BDL)) and ACLF models (induced by lipopolysaccharide (LPS) to BDL) were studied. BDL groups: ±LPS, ±albumin infusion (1.5 g/kg i.p. for 2 weeks). Markers of liver injury: plasma ALT level and TUNEL staining; markers of gut integrity and permeability: DAB immunohistochemistry ZO-1 expression in ileum tissue; Hepatic TLR4 immunohistochemistry and related pathway genes RT2 PCR profiler were studied. <h3>Results</h3> Liver injury: ALT levels and TUNEL positive areas were significantly higher in NAR compared with SD rats (p = 0.01 and p = 0.01), which were corrected with albumin infusion (p = 0.02, p = 0.047). Effect of LPS administration: coma-free survival was higher in SD rats than NAR rats (80% vs 40%). Effect of albumin administration: Administration of albumin to BDL rats reduced severity of liver injury and mortality after LPS administration [p = 0.001; 40% vs 100%, p = 0.04]. Markers of gut permeability: In NAR rats, the histopathological examination of the ileum and colon revealed a reduction in ZO-1 expression, which was restored with albumin supplementation (figure 1). Hepatic expression of TLR4 and associated pathways: Cirrhotic NAR animals had greater hepatic TLR4 expression which was reduced by albumin administration. Hepatic TLR4 gene array confirmed the activation of TLR4 dependent pathways in the cirrhotic NAR animals, which was abrogated by albumin infusion. <h3>Conclusion</h3> NAR animals have significantly greater liver injury, increased sensitivity to LPS and mortality which is prevented by albumin administration. Our data show for the first time that the mechanism of the protective effect of albumin is consequent upon restoration of gut junctional proteins and reduction of hepatic TLR4 expression.