Portal vein stenosis preconditioning of living donor liver in swine: early mechanisms of liver regeneration and gain of hepatic functional mass

Abstract

To reduce the morbidity and mortality risk for the donor in living donor liver transplantation (LDLT), we previously identified 20% left portal vein (LPV) stenosis as an effective preconditioning method to induce cell proliferation in the contralateral lobe without downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours after preconditioning and investigate the changes in liver volume and function. Fourteen pigs were used this study. Five pigs were used to study the genetic, cellular and molecular mechanisms set up in the early hours following the establishment of our preconditioning. The remaining nine pigs were equally divided into three groups: sham-operated animals, 20% LPV stenosis, and 100% LPV stenosis. Volumetric scanning and 99 mTc-Mebrofenin hepatobiliary scintigraphy were performed before preconditioning and 14 days after to study morphological and functional changes in the liver. We demonstrated that liver regeneration triggered by 20% LPV stenosis in the contralateral lobe involves TNF-α, IL-6, and inducible nitric oxide synthase 2 by means of STAT3 and hepatocyte growth factor. We confirmed that our preconditioning was responsible for an increase in the total liver volume. Finally, we demonstrated that this volumetric gain was associated with an increase in hepatic functional capacity. NEW & NOTEWORTHY We describe a new preconditioning method for major hepatectomy that is applicable to hepatectomy for donation. We identified 20% left portal vein stenosis as effective preconditioning that is capable of inducing cell proliferation in the contralateral lobe without the downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours following preconditioning, and we confirm that 20% left portal vein stenosis is responsible for an increase in the functional capacity and total liver volume in a porcine model.