AnimalModelsofFibrosisinNonalcoholic Steatohepatitis:DoTheyReflectHumanDisease

Abstract

Nonalcoholic steatohepatitis (NASH) is one of the most common chronic liver diseases in the world, yet no pharmacotherapies are available. The lack of translational animal models is a major barrier impeding elucidation of disease mechanisms and drug development. Multiple preclinical models of NASH have been proposed and can broadly be characterized as diet-induced, deficiency-induced, toxin-induced, genetically induced, oracombinationofthese.However,veryfewmodelsdevelopadvancedfibrosiswhilestillreflectinghumandiseaseetiologyorpathology,whichis problematicsincefibrosisstageisconsideredthebestprognosticmarkerinpatientsandanimportantendpointinclinicaltrialsofNASH.Whilemice andratspredominatetheNASHresearch,severalotherspecieshaveemergedaspromisingmodels.Thisreviewcriticallyevaluatesanimalmodels ofNASH,focusingontheirabilitytodevelopadvancedfibrosiswhilemaintainingtheirrelevancetothehumancondition