Does steatohepatitis impair liver regeneration? A study in a dietary model of non-alcoholic steatohepatitis in rats

Background: Impaired liver regeneration is a feature of alcoholic hepatitis, but the relative importance of alcohol, nutritional imbalance and inflammatory mediators in causing this effect is unclear. Nonalcoholic steatohepatitis (NASH) is a form of liver disease with similar morphology to alcoholic hepatitis, but the effect of this disorder on liver regeneration is unclear. We, therefore, examined the status of liver regeneration in a rat nutritional model of hepatic steatosis with inflammation, which is morphologically identical to NASH in humans. Methods: Male Wistar rats received a methionine-choline-deficient diet (MCDD) for 4 weeks before experiments and both isocaloric pair-fed and ad libitum-fed rats were used as controls. Following partial hepatectomy (68%), the extent of hepatic regeneration was determined 24 h later using [H-3]-thymidine incorporation and restitution of liver mass. Results: There was no significant difference of [3H]-thymidine incorporation in MCDD-fed, pair-fed and ad libitum-fed rats (80 +/- 27, 78 +/- 11 and 80 +/- 6.3 d.p.m./mu g DNA, respectively). Similarly, restituted liver masses in three groups of rats were not significantly different (17 +/- 3.8, 18 +/- 1.8 and 17 +/- 3.1% initial liver weight, respectively). Conclusions: The similarities in hepatic histology and cytochrome P450 2E1 induction between this nutritional model of hepatic steatohepatitis and alcoholic steatohepatitis imply that these two disorders share pathogenetic mechanisms. However, liver regeneration is not altered by NASH in rats, indicating that the nutritional and inflammatory changes that appear similar to those of alcoholic liver disease do not cause impairment of liver regeneration.