Fate of the human liver after hemihepatic portal vein embolization: cell kinetic and morphometric study

Abstract

The favorable therapeutic effect of preoperative portal vein embolization (PVE) was analyzed by assessing various volumetric, cell kinetic and morphometric parameters and examining histologically the embolized and nonembolized lobes of 15 patients who underwent extended right lobectomy 2 to 3 weeks after PVE. Each lobar volume was calculated from computed tomography (CT) images, hepatocyte proliferation was evaluated by assessing proliferative cell nuclear antigen (PCNA) expression and mitosis, hepatocyte apoptosis was evaluated by the terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the hepatocyte numerical density as well as the sinusoidal volumetric ratio (Vvs) and the mean hepatocyte volume (Cv) were calculated using morphometric methods. PVE induced hepatocyte apoptosis and atrophy of the embolized lobe (from 798 +/- 213 to 708 +/- 222 cm3; P < .05). The increased sinusoidal volume in this lobe (17.7% +/- 4.5% and 21.7% +/- 5.7%, periportal and pericentral area, respectively) may have been attributable to hepatocyte deletion. Cells in the nonembolized lobe entered a highly active phase of proliferation within 2 weeks after PVE. Further evidence of cellular proliferation was provided by the increased nonembolized lobar volume (from 379 +/- 132 to 545 +/- 130 cm3; P < .01) and numerical density of hepatocyte nuclei (Nv) (5.38 +/- 1.26 vs. 3.11 +/- 0.85 x 10(5)/mm3; P < .01, nonembolized vs. embolized lobe, respectively). In conclusion, these results indicate that the favorable effect of PVE is attributable to a net gain of functional hepatocyte mass and/or early induction of hepatocyte proliferation following hepatectomy.