Comparative study of the effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats

Abstract

Background: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70% partial hepatectomy.

Methods: Seventy-two male Wistar rats were randomly assigned into three groups (n=24 in each group): 70% partial hepatectomy as control (PHC), 70% partial hepatectomy with splenectomy (PHS) or 70% partial hepatectomy with a micropump for terlipressin administration (PHT). Eight rats in each group were sacrificed on postoperative day (POD) 1, 3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine (BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and 7.

Results: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups (PHT: 8.13±1.55, 10.38±1.30, 6.25±0.89 cmH₂O and PHS: 7.50±0.93, 8.88±2.42, 5.75±1.04 cmH₂O) was lower compared to the control group (PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmH₂O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1 (BrdU: PHS vs PHC, 20.85%±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96%±11.69%). However, none of the differences were statistically significant.

Conclusions: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of liver regeneration.

Keywords: hepatectomy; liver failure; liver regeneration; splenectomy; terlipressin.