Cell-to-Cell Communications in Alcohol-Associated Liver Disease

Natalia A. Osna, Akiko Eguchi, Ariel E. Feldstein, Hidekazu Tsukamoto, Raghubendra S. Dagur, Murali Ganesan, Moses New-Aaron, Madan Kumar Arumugam, Srinivas Chava, Marcelle Ribeiro, Gyongyi Szabo, Sebastian Mueller, Shijin Wang, Cheng Chen, Steven A. Weinman, Kusum K. Kharbanda

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations


This review covers some important new aspects of the alcohol-induced communications between liver parenchymal and non-parenchymal cells leading to liver injury development. The information exchange between various cell types may promote end-stage liver disease progression and involves multiple mechanisms, such as direct cell-to-cell interactions, extracellular vesicles (EVs) or chemokines, cytokines, and growth factors contained in extracellular fluids/cell culture supernatants. Here, we highlighted the role of EVs derived from alcohol-exposed hepatocytes (HCs) in activation of non-parenchymal cells, liver macrophages (LM), and hepatic stellate cells (HSC). The review also concentrates on EV-mediated crosstalk between liver parenchymal and non-parenchymal cells in the settings of HIV- and alcohol co-exposure. In addition, we overviewed the literature on the crosstalk between cell death pathways and inflammasome activation in alcohol-activated HCs and macrophages. Furthermore, we covered highly clinically relevant studies on the role of non-inflammatory factors, sinusoidal pressure (SP), and hepatic arterialization in alcohol-induced hepatic fibrogenesis. We strongly believe that the review will disclose major mechanisms of cell-to-cell communications pertained to alcohol-induced liver injury progression and will identify therapeutically important targets, which can be used for alcohol-associated liver disease (ALD) prevention.

Original languageEnglish (US)
Article number831004
JournalFrontiers in Physiology
StatePublished - Feb 21 2022


  • HIV
  • alcohol hepatitis
  • extracellular vesicles
  • fibrosis
  • liver stiffness
  • pyroptosis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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