The present disclosure provides co-cultures of a population of hepatocytes, at least one non-parenchymal cell population, and a population of hepatic stellate cells in vitro, methods of preparing the co-cultures, and methods of using the co-cultures for high throughput screening and evaluation of drug candidates. The hepatocytes co-culture system provides an in vitro model in which both cell viability and phenotype are maintained for extended periods relative to conventional monoculture.