Liver Organoid and Liver-On-A-Chip Platforms for Modeling Alcoholic Liver Disease: A Comparative Review.

Abstract

Alcoholic liver disease (ALD) encompasses a spectrum of progressive liver injuries caused by chronic alcohol consumption, including steatosis, hepatitis, fibrosis, and cirrhosis. The development of physiologically relevant preclinical models remains critical for elucidating the pathogenesis of ALD and evaluating therapeutic strategies. Recent advances in liver organoid and liver-on-a-chip (LOC) technologies offer complementary platforms for modeling distinct aspects of ALD. Organoids recapitulate liver tissue architecture with multicellular composition, enabling the study of chronic pathological processes such as lipid accumulation and early fibrogenesis. Conversely, LOC systems replicate dynamic microenvironments such as fluid flow and oxygen gradients, enabling studies of inflammation and vascular injury. In this review, the first comprehensive comparison of liver organoids and LOC systems specifically in the context of ALD is provided. Emerging liver organoid-on-a-chip (OoC) strategies and their potential to model the full spectrum of ALD pathology are also discussed. Finally, key technical challenges are identified, and future directions are proposed targeting patient-specific, multiorgan, and high-throughput platforms to advance ALD-related research and precision medicine.