Hypoxia protects the liver from Small For Size Syndrome: A lesson learned from the associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure in rats.

Dili, Alexandra;Claude, Bertrand;Lebrun, Valérie;Pirlot, Boris;Leclercq, Isabelle
(2019) American Journal of Transplantation — Vol. 19, n° 11, p. 2979-2990 (2019)

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Abstract
Portal hyperperfusion and "dearterialization" of the liver remnant are the main pathogenic mechanisms for Small For Size syndrome (SFSS). Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces rapid remnant hypertrophy. We hypothesized a similar increase in portal pressure/flow into the future liver remnant in ALPPS and SFSS-setting hepatectomies. In a rodent model, ALPPS was compared to SFSS-setting hepatectomy. We assessed mortality, remnant hypertrophy, hepatocyte proliferation, portal and hepatic artery flow, hypoxia-induced response, and liver sinusoidal morphology. SFSS-hepatectomy rats were subjected to local (hepatic artery ligation) or systemic (Dimethyloxalylglycine) hypoxia. ALLPS prevented mortality in SFSS-setting hepatectomies. Portal hyperperfusion per liver mass was similar in ALLPS and SFSS. Compared to SFSS, efficient arterial perfusion of the remnant was significantly lower in ALPPS causing pronounced hypoxia confirmed by pimonidazole immunostaining, activation of hypoxia sensors and upregulation of neo-angiogenic genes. Liver sinusoids, larger in ALPPS, collapsed in SFSS. Induction of hypoxia in SFSS reduced mortality. Hypoxia had no impact on hepatocyte proliferation but contributed to the integrity of sinusoidal morphology. ALPPS hemodynamically differ from SFSS by a much lower arterial flow in ALPPS's FLR. We show that the ensuing hypoxic response is essential for the function of the regenerating liver by preserving sinusoidal morphology.
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Dili, A., Claude, B., Lebrun, V., Pirlot, B., & Leclercq, I. (2019). Hypoxia protects the liver from Small For Size Syndrome: A lesson learned from the associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure in rats. American Journal of Transplantation, 19(11), 2979-2990. https://doi.org/10.1111/ajt.15420 (Original work published 2019)