{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:09:19Z","timestamp":1740146959632,"version":"3.37.3"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:00:00Z","timestamp":1703808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["grant number 182471"],"award-info":[{"award-number":["grant number 182471"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Association de soutien \u00e0 la Paralysie Supranucl\u00e9aire ProgressiveFondation Francis & Marie-France Minkoff"},{"DOI":"10.13039\/501100007673","name":"Fondation Centre de Recherches M\u00e9dicales Carlos et Elsie de Reuter","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007673","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondation Gilles Mentha"},{"name":"Swiss Society of Gastroenterology"},{"name":"the Swiss Society of Visceral Surgery"},{"DOI":"10.13039\/501100006387","name":"Fondation Leenaards","doi-asserted-by":"publisher","award":["5489"],"award-info":[{"award-number":["5489"]}],"id":[{"id":"10.13039\/501100006387","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background and aims<\/jats:title>\n<jats:p>Non-alcoholic fatty liver disease (NAFLD) is one of the leading cause of hepatocellular carcinoma (HCC). This association is supported by the translocation of bacteria products into the portal system, which acts on the liver through the gut-liver axis. We hypothesize that portosystemic shunting can disrupt this relationship, and prevent NAFLD-associated HCC.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>HCC carcinogenesis was tested in C57BL\/6 mice fed a high-fat high-sucrose diet (HFD) and injected with diethylnitrosamine (DEN) at two weeks of age, and in double transgenic LAP-tTA and TRE-MYC (LAP-Myc) mice fed a methionine-choline-deficient diet. Portosystemic shunts were established by transposing the spleen to the sub-cutaneous tissue at eight weeks of age.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Spleen transposition led to a consistent deviation of part of the portal flow and a significant decrease in portal pressure. It was associated with a decrease in the number of HCC in both models. This effect was supported by the presence of less severe liver steatosis after 40 weeks, and lower expression levels of liver fatty acid synthase. Also, shunted mice exhibited lower liver oxygen levels, a key factor in preventing HCC as confirmed by the development of less HCCs in mice with hepatic artery ligation.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The present data show that portosystemic shunting prevents NAFLD-associated HCC, utilizing two independent mouse models. This effect is supported by the development of less steatosis, and a restored liver oxygen level. Portal pressure modulation and shunting deserve further exploration as potential prevention\/treatment options for NAFLD and HCC.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0296265","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T18:26:45Z","timestamp":1703874405000},"page":"e0296265","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Portosystemic shunting prevents hepatocellular carcinoma in non-alcoholic fatty liver disease mouse 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