Multiple factors/mechanisms are involved in ALD pathogenesis. Alcoholic liver injury can lead to a broad range of liver abnormalities. Alcohol is primarily metabolized in the hepatocyte leading to increased secretion of inflammatory mediators which, in turn, activate and/or influence the response of the nonparenchymal cells (NPCs) (hepatic stellate cells, Kupffer cells, and sinusoidal endothelial cells) and subsequently degree of liver injury. Liver also serves as immune organ and accommodates a wide variety of cells, including immune cells. The latter includes dendritic cells (DCs), natural killer (NK) cells, and lymphocytes that are present in normal livers. Selective recruitment and retention of certain immune populations occur during diverse liver diseases, and these cells play a critical role in development and resolution of liver inflammation, remodeling, and destruction. In addition, liver cells are known to actively participate in immune defense. One of the mechanisms which affects various liver cell types and affects disease progression is an impairment of methylation reactions. The various biological functions that are modulated by methylation reactions include proteasome functions, antigen presentation, interferon signaling, intracellular fat mobilization, cell signaling, apoptosis control, and epigenetic changes in hepatocytes. Hepatic stellate cell activation and TNFα expression in macrophages are other phenomena that appear to be affected by alterations in methylation reactions. In addition, inclusion of treatment modalities with betaine and SAM, two agents that can correct methylation defects to attenuate many ethanol-induced liver changes, will also be solicited.

We invite investigators to contribute original research articles as well as review articles that cover these aspects of ALD. Potential topics include, but are not limited to:

• Nonparenchymal cells in development and progression of ALD
• Modulation of fibrogenic gene expression
• HSC transdifferentiation, matrix remodeling, reversal of HSC to quiescent state
• Liver as immune organ: implications for alcohol-induced liver pathology
• The mechanisms of recruitment, trafficking, retention, and activity of immune cells to the liver
• The role of miRNA and other small RNAs in the regulation of gene expression in ALD
• Methylation defects in ALD: pathogenesis and treatment

Articles published in this special issue will not be subject to the journal's Article Processing Charges.

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