The alcoholic liver disease involves cascading events, initiating from alcoholic fatty liver, and then mostly via alcoholic steatohepatitis or alcoholic hepatitis progressing potentially to cirrhosis and hepatocellular carcinoma. 

Pathogenetic affairs are connected with the metabolism of ethanol and acetaldehyde as its first oxidation product generated via hepatic alcohol dehydrogenase (ADH) and the microsomal ethanol-oxidizing system (MEOS), which depends on cytochrome P450 2E1 (CYP 2E1), and is provoked by chronic alcohol use. MEOS provocation fastens the metabolism of ethanol to acetaldehyde that promotes organ injury including the liver. In association with CYP 2E1, it also produces many reactive oxygen species (ROS) such as ethoxy radical, hydroxyethyl radical, acetyl radical, singlet radical, superoxide radical, hydrogen peroxide, hydroxyl radical, alkoxyl radical, and peroxyl radicals, which in turn attacks hepatocytes, Kupffer cells, stellate cells, and liver sinusoidal endothelial cells, along with their signaling mediators like interleukins, interferons, and growth factors. These events trigger liver injury including fibrosis and cirrhosis in susceptible individuals with specific risk factors. 

Through CYP 2E1-dependent ROS, evidence suggests that alcohol generates lipid peroxides and modifies the intestinal microbiome, thus boosting the actions of endotoxins produced by intestinal bacteria. Lipid peroxides and endotoxins are primarily involved in alcoholic liver injury. 

Alcohol modifies SIRT1 (Sirtuin-1; derived from Silent mating type Information Regulation) and SIRT2, along with the innate and adapted immune systems, which explains the individual discrepancies of injury susceptibility. Metabolic pathways are also affected by circadian rhythms, characteristic conditions known from living organisms including plants. 

More literature is needed on a 5-hit working hypothesis, trying to describe key elements concerned with injury progression. 

However, many biochemical mechanisms are suggested for the initiation and perpetuation of liver injury, patients with an alcohol problem can benefit from permanent alcohol abstinence alone.

Source- Biomedicines 2018, 6(4), 106; https://doi.org/10.3390/biomedicines6040106