Size regulation of portally deprived liver lobe and future liver remnant following simultaneous portal vein ligation and partial hepatectomy

Partial hepatectomy (PHx) remains the only curative treatment for patients with malignant liver tumors. Due to the hepatic injury and the inadequate size of future liver remnant (FLR) after liver resection, major hepatectomy is associated with a high risk of post-hepatectomy liver failure. To expand the indications for surgical treatment for patients with primarily irresectable liver tumors, portal vein occlusion prior to major hepatectomy is adopted in liver surgery. However, there is no well-characterized experimental model to study the underlying regulatory mechanism. We designed a surgical model consisting of simultaneous portal vein ligation (PVL) and PHx to study intrahepatic size regulation. Rats were subjected to two experimental procedures: either simultaneous 20%PVL and 70%PHx or simultaneous 70%PVL and 20%PHx. For control, 20% PVL, 70%PVL and 90% PVL alone were performed. The hypertrophy of the FLR and atrophy of the ligated liver lobe were evaluated. Liver enzyme, hepatocyte proliferation, apoptosis and autophagy related parameters were assessed. Our experimental model is suitable to investigate intrahepatic size regulation following simultaneous PVL and PHx. The observations of this study showed that the ligated liver lobes underwent atrophy after PVL. However, atrophy of the ligated liver lobes was counteracted by additional PHx. Even more, the ligated liver lobes developed substantial hypertrophy after additional large resection due to the induction of hepatocyte proliferation. Autophagy was activated in both ligated and non-ligated liver lobes, accompanied by suppression of apoptosis and promotion of proliferation. In conclusion, intrahepatic size regulation is the results of balancing proliferation, apoptosis and autophagy. The expected findings of the planned study may contribute to a novel strategy which accelerates the hypertrophy of FLR by modulating autophagy and therefore expand the indications for extended hepatectomy following PVL.