Published online Jan 7, 2021. doi: 10.3748/wjg.v27.i1.1
Peer-review started: September 3, 2020
First decision: October 17, 2020
Revised: November 1, 2020
Accepted: December 6, 2020
Article in press: December 6, 2020
Published online: January 7, 2021
Processing time: 114 Days and 18.8 Hours
Non-alcoholic fatty liver disease (NAFLD) is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome (MetS). Because alcohol consumption in NAFLD patients is common, there is a significant overlap in the pathogenesis of NAFLD and alcoholic liver disease (ALD). Indeed, MetS also significantly contributes to liver injury in ALD patients. This “syndrome of metabolic and alcoholic steatohepatitis” (SMASH) is thus expected to be a more prevalent presentation in liver patients, as the obesity epidemic continues. Several pre-clinical experimental models that couple alcohol consumption with NAFLD-inducing diet or genetic obesity have been developed to better understand the pathogenic mechanisms of SMASH. These models indicate that concomitant MetS and alcohol contribute to lipid dysregulation, oxidative stress, and the induction of innate immune response. There are significant limitations in the applicability of these models to human disease, such as the ability to induce advanced liver injury or replicate patterns in human food/alcohol consumption. Thus, there remains a need to develop models that accurately replicate patterns of obesogenic diet and alcohol consumption in SMASH patients.
Core Tip: Experimental animal and cell culture models have been developed to study the “syndrome of metabolic and alcoholic steatohepatitis” (SMASH), in which concomitant non-alcoholic fatty liver disease and alcoholic liver disease risk factors play a role in liver injury. These models demonstrate that obesity, metabolic syndrome, and alcohol consumption synergistically contribute to lipid dysregulation, oxidative stress, inflammation, and fibrogenesis. The pathogenesis of SMASH in these experimental models is dependent on obesogenic diet composition, alcohol consumption patterns, alcohol dosage, and genetic background.