Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.8
Peer-review started: October 13, 2017
First decision: November 7, 2017
Revised: November 20, 2017
Accepted: December 6, 2017
Article in press: December 6, 2017
Published online: January 27, 2018
To evaluate the liver regeneration capacity (LRC) after partial hepatectomy (PH) in experimental non-alcoholic steatohepatitis (NASH).
Fifty-four female rats were fed a high-fat, high-cholesterol diet (HFCD, 65% fat, 1% cholesterol) or standard diet (STD) for 16 wk. A 70% PH was performed and the animals were euthanised before PH or 2 or 5 d post-PH. LRC was evaluated using: The total number of Ki-67 positive hepatocytes in the caudate lobe, N(Ki-67, lobe) evaluated in a stereology-based design, the regenerated protein ratio (RPR), prothrombin-proconvertin ratio (PP), and mRNA expression of genes related to regeneration.
The HFCD NASH model showed significant steatosis with ballooning and inflammation, while no fibrosis was present. Mortality was similar in HFCD and STD animals following PH. HFCD groups were compared to respective STD groups and HFCD animals had a significantly elevated alanine transaminase at baseline (P < 0.001), as well as a significantly elevated bilirubin at day 2 after PH (P < 0.05). HFCD animals had a higher N(Ki-67, lobe) at baseline, (P < 0.0001), day 2 after PH (P = 0.06) and day 5 after PH (P < 0.025). We found no significant difference in RPR or PP neither 2 or 5 d post-PH. Expression of liver regeneration genes (e.g., hepatic growth factor) was higher at both day 2 and 5 post-PH in HFCD groups (P < 0.05).
NASH rats had a preserved LRC after hepatectomy when compared to STD rats. The methods and models of NASH are essential in understanding and evaluating LRC.
Core tip: Liver regeneration capacity has been studied in different animal models of non-alcoholic steatohepatitis. This study is the first to use a high fat high cholesterol model which mimic the pathogenesis of human non-alcoholic steatohepatitis better than previous animal models. Liver regeneration capacity was evaluated using: (1) The total number of Ki-67 positive hepatocytes in the caudate lobe, evaluated in a stereology based design; (2) the regenerated protein content to describe the regenerated liver mass; and (3) the plasma concentration of coagulation factors as a marker of liver function. We found a preserved liver regeneration capacity in rats with non-alcoholic steatohepatitis, adding important knowledge to the subject.