Evaluation of safety for hepatectomy in a novel mouse model with nonalcoholic-steatohepatitis.

Abstract

AIMTo investigate whether the liver resection volume in a newly developed nonalcoholic steatohepatitis (NASH) model influences surgical outcome.METHODSFor establishment of a NASH model, mice were fed a high-fat diet for 4 wk, administered CCl4 for the last 2 wk, and administered T0901317 for the last 5 d. We divided these mice into two groups: A 30% partial hepatectomy (PH) of NASH liver group and a 70% PH of NASH liver group. In addition, a 70% PH of normal liver group served as the control. Each group was evaluated for survival rate, regeneration, apoptosis, necrosis and DNA expression after PH.RESULTSIn the 70% PH of NASH group, the survival rate was significantly decreased compared with that in the control and 30% PH of NASH groups (P < 0.01). 10 of 32 mice in the NASH 70% PH group died within 48 h after PH. Serum aspartate aminotransferase (AST) levels and total bilirubin (T-Bil) in the NASH 70% PH group were significantly higher than the levels in the other two groups (AST: P < 0.05, T-Bil: P < 0.01). In both PH of NASH groups, signaling proteins involved in regeneration were expressed at lower levels than those in the control group (P < 0.01). The 70% PH of NASH group also exhibited a lower number of Ki-67-positive cells and higher rates of apoptosis and necrosis than the NASH 30% PH group (P < 0.01). In addition, DNA microarray assays showed differences in gene expression associated with cell cycle arrest and apoptosis.CONCLUSIONThe function of the residual liver is impaired in fatty liver compared to normal liver. A larger residual volume is required to maintain liver functions in mice with NASH.