Nearly every individual chronically exposed to alcohol will develop fatty liver but only a minority progresses up to cirrhosis. Duration and amount of alcohol ingestion is the most important risk factor for the development of a progressive form of alcohol-dependent liver disease.

Female sex, obesity, non-sex-linked genetic factors and cigarette smoking are considered the risk factors and modulators of the host susceptibility to develop and progress ALD. Further, alcohol also synergistically interacts with other causative agents of liver damage such as hepatitis virus B or C and/or human immunodeficiency virus infection, nonalcoholic fatty liver disease, and disorders such as hemochromatosis to promote the progression of alcohol-related liver injury.

Liver damage by directly triggering inflammation, extracellular matrix (ECM) remodeling and fibrogenesis is caused by Acetaldehyde. Alcohol consumption also causes significant hypoxia of the perivenous hepatocytes ultimately resulting in damage.

The pancreas is involved in the metabolism of ethanol-producing metabolites and byproducts that injure the acinar cells and stimulation of stellate cells to produce and deposit ECM. Acetaldehyde and ROS cause microtubular dysfunction and actin cytoskeleton disruption, alteration in the intracellular redox state and destabilization of zymogen granules and lysosomes. FAAEs directly interact with cellular membranes, stimulate cholesteryl ester synthesis and free fatty acids release with consequent mitochondrial damage. They also induce activation of NF-κB and AP-1 transcription factors and alteration of intracellular calcium metabolism.

Alcohol or its components may cause (1) inflammation in the esophageal and gastric mucosa; (2) Sphincterial pressure modification and motility impairment; and (3) gastric acid output alteration. 

Ethanol stimulates ET-1 secretion and inhibits NO and PGE2 synthesis and secretion thus damaging the gastric mucosa and weakening its ability to repair.

Source: Rocco A, Compare D, Angrisani D, Sanduzzi Zamparelli M, Nardone G. Alcoholic disease: liver and beyond. World J Gastroenterol. 2014;20(40):14652-14659. doi:10.3748/wjg.v20.i40.14652