Hepatic Hypertrophy in Normal and Cirrhotic Livers Following Portal Vein Embolization: Comparative Assessment of 2 Different Embolic Regimens in a Large Animal Model

Abstract

Purpose: To compare the mechanistic effects and hypertrophy outcomes using 2 different portal vein embolization (PVE) regimens in normal and cirrhotic livers in a large animal model.

Methods and materials: The Institutional Animal Care and Use Committee approved all experiments conducted in this study. Fourteen female Yorkshire pigs were separated into a cirrhotic group (CG, n = 7) and non-cirrhotic group (NCG, n = 7) and further subgrouped into those using microspheres and coils (MC, n = 3) or n-butyl cyanoacrylate (nBCA, n = 3) and their corresponding controls (each n = 1). A 3:1 ethiodized oil and ethanol mixture was administered intra-arterially in the CG to induce cirrhosis 4 weeks before PVE. Animals underwent baseline computed tomography (CT), PVE including pre-PVE and post-PVE pressure measurements, and CT imaging at 2 and 4 weeks after PVE. Immunofluorescence stainings for CD3, CD16, Ki-67, and caspase 3 were performed to assess immune cell infiltration, hepatocyte proliferation, and apoptosis. Statistical significance was tested using the Student's t test.

Results: Four weeks after PVE, the percentage of future liver remnant (FLR%) increased by 18.8% (standard deviation [SD], 3.6%) vs 10.9% (SD, 0.95%; P < .01) in the NCG vs CG. The baseline percentage of standardized future liver remnant (sFLR%) for the controls were 41.6% for CG vs 43.6% for NCG. Based on the embolic agents used, the sFLR% two weeks after PVE was 58.4% (SD, 3.7%) and 52.2% (SD, 0.9%) (P < .01) for MC and 46.0% (SD, 2.2%) and 47.2% (SD, 0.4%) for nBCA in the NCG and CG, respectively. Meanwhile, the sFLR% 4 weeks after PVE was 60.5% (SD, 3.9%) and 54.9% (SD, 0.8%) (P < .01) and 60.4% (SD, 3.5%) and 54.2% (SD, 0.95%) (P < .01), respectively. Ki-67 signal intensity increased in the embolized lobe in both CG and NCG (P < .01).

Conclusions: This preclinical study demonstrated that MC could be the preferred embolic of choice compared to nBCA when a substantial and rapid FLR increase is needed for resection, in both cirrhotic and non-cirrhotic livers.