Published online Apr 21, 2018. doi: 10.3748/wjg.v24.i15.1622
Peer-review started: February 14, 2018
First decision: March 9, 2018
Revised: March 16, 2018
Accepted: March 25, 2018
Article in press: March 25,2018
Published online: April 21, 2018
The population of patients with nonalcoholic steatohepatitis (NASH) and NASH-related hepatocellular carcinoma (HCC) has been increasing. However, few animal models fully reflect both the histopathology and pathophysiology of NASH in humans, therefore, the metabolism of the residual liver after a hepatectomy with NASH has not been clarified. We succeeded to establish a novel experimental NASH model that had same characteristics of histopathology and pathophysiology of NASH in humans.
In NASH, continuous inflammation contributes to HCC. The cause of HCC is frequently infection with hepatitis B virus and hepatitis C virus (HCV). New antiviral medications for hepatitis are currently being used in clinics; therefore, the number of patients with virus-related HCC is expected to decrease in the future. By contrast, the number of patients with NASH-related HCC has been increasing recently, and this trend is expected to continue because no effective treatments are available
The aim of this study was to investigate whether a difference in liver resection volume in a novel NASH model influences surgical outcomes.
To 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. These mice were divided into two groups: A 30% partial hepatectomy (PH) of NASH liver group and a 70% PH of NASH liver group (control). Evaluate the survival rate, regeneration, apoptosis, necrosis and DNA expression level after PH.
In 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.
The residual NASH liver dysfunction after hepatectomy is attributed to a reduction in liver regeneration and cell proliferation. A larger residual volume is required to maintain liver functions in mice with NASH.
This study suggests that the resection volume is a more limiting factor in patients with NASH than in those with a normal liver. Regarding liver surgery, the risk of complications for patients diagnosed with NASH by liver biopsy should be determined before hepatectomy. Further studies are needed to clarify therapeutic agents for NASH using our novel NASH model.