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Preserved liver regeneration capacity after partial hepatectomy in rats with non-alcoholic steatohepatitis
Authors:David Haldrup  Sara Heeb&#  ll  Karen Louise Thomsen  Kasper Jarlhelt Andersen  Michelle Meier  Frank Viborg Mortensen  Jens Randel Nyengaard  Stephen Hamilton-Dutoit  Henning Gr&#  nb&#  k
Abstract:AIM To evaluate the liver regeneration capacity(LRC) after partial hepatectomy(PH) in experimental non-alcoholic steatohepatitis(NASH).METHODS 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 postPH. 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 m RNA expression of genes related to regeneration.RESULTS 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).CONCLUSION 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.
Keywords:Rat   Non-alcoholic fatty liver   Non-alcoholic steatohepatitis   Liver regeneration   Hepatectomy   Ki-67   Gene expression
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