Normal and fibrotic liver parenchyma respond differently to irreversible electroporation ablation

Abstract

Background: Irreversible electroporation (IRE) is emerging as a tumor ablation modality and its safety and efficacy for treating hepatic, biliary, and pancreatic malignancies are active areas of clinical investigation. For tumors of the liver that may be treated by ablation, colorectal metastases most often occur within normal liver parenchyma, whereas hepatocellular carcinoma more commonly arise in the setting of liver fibrosis. It is currently unknown how fibrotic tissue may modulate the response to IRE treatment. In this study, we aim to characterize the electrical properties of normal and fibrotic liver tissue and their response to IRE ablation. Methods: C57BL/6 mice with liver fibrosis induced by 0.1% 3,5-diethylcarbonyl-1,4- dihydrocollidine (DDC) diet were compared to matched control mice with normal liver. The electrical impedance of normal and fibrotic mouse liver was measured “in vivo” at baseline. IRE treatment was then administered and “in vivo” impedance of the IRE-treated liver parenchyma measured over a time course. Histological analysis of normal and fibrotic liver after IRE treatment was also performed. Results: The electrical impedance of normal and fibrotic liver was comparable at baseline. Immediately after IRE treatment, there was a significant decrease in impedance in normal liver but not in fibrotic liver. Upon histological analysis, the electric field strength that induced tissue injury in normal liver did not induce injury in the fibrotic liver. Conclusion: Normal and fibrotic liver tissue respond to IRE treatment differently. Fibrotic liver may be more resistant to IRE ablation, which may be important to consider when designing IRE ablation regimens for hepatocellular carcinoma that most commonly occur in fibrotic liver.