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Irinotecan-induced Non-alcoholic Steatohepatitis: The Role of Gut Bacterial Translocation

2016; Elsevier BV; Volume: 18; Linguagem: Inglês

10.1016/j.hpb.2016.02.755

1477-2574

Marcelo Leite Vieira Costa, Karoline S. Aragão, Roberto César Pereira Lima Júnior, José Wilson Benevides de Mesquita Neto, Gerly Anne de Castro Brito, M.H.L.P.d. Souza, Anielle Torres de Melo, Heitor Amorim Muniz, Carlos Diego Holanda Lopes, Luciane Dellazari da Silva do Prado, Cibele Barreto Mano de Carvalho, Paulo Roberto Carvalho de Almeida, Rita A. Ribeiro,

Hepatocellular Carcinoma Treatment and Prognosis

Introduction: Postoperative liver failure is a major concern after hepatic resection. Non-alcoholic steatohepatitis (NASH) is a predictor of liver failure and can be induced by the commonly used irinotecan-based chemotherapy regimens. The precise mechanism by which irinotecan (IRI) leads to inflammation and ultimately fibrosis is not completely understood, therefore there is no effective pharmacologic approach to prevent NASH. Recently, the changes in gut microbiota and their association with the expression of Toll-like receptors (TLR) ligands have been advocated to play a major role in NASH. The purpose of this study was to investigate whether there is a role for gut bacterial translocation in the pathogenesis of IRI-induced NASH. Method: According to our previously published model, IRI-induced NASH was induced by injecting swiss male mice with saline (5 mL/kg, i.p.; control) or IRI (50 mg/kg, i.p.) thrice a week for 7 weeks. Cultures of portal vein and ocular plexus blood were performed and serum concentrations of proteins, ALT and AST were measured. Immunohistochemistry analysis for TLR-4, IL-1, IL-18 and NOSi were performed in liver and duodenum tissues. Results: In all mice that developed NASH and mucositis, the cultures were positive for gram negative bacteria (Escherichia coli) in both portal and orbital blood. It was also demonstrated elevated imunostaining for TLR-4, IL-1 and iNOS in both liver and duodenal samples. The cultures were negative in all controls. Conclusions: Translocation of gram-negative intestinal bacteria, namely E. coli, leading to portal bacteremia may represent the very first hepatic insult of IRI-induced NASH.