The objectives of this research were to investigate 1) if hepatic steatosis and nonalcoholic steatohepatitis (NASH) independently sensitize the liver to hepatotoxicity and 2) the mechanisms behind the increased sensitivity.Our study suggests that fatty hepatocytes fail to undergo compensatory cell division rendering the liver susceptible to progressive expansion of liver injury. In conclusion, impaired tissue repair response sensitizes the steatotic/steatohepatitic livers to hepatotoxicity.