Alcohol and Liver Disease

Alcohol-induced disorders have become a serious health problem in the United States. About 7.1% of Americans older than 18 years meet the criteria for alcohol abuse. Alcohol provides damaging effects on most organs and systems in the body, especially the nervous and hepatogastrointestinal systems. Alcohol abuse is frequently associated with an accelerated progression of alcoholic liver disease (ALD), in which steatohepatitis progresses to liver fibrosis, followed by cirrhosis and an increased incidence of hepatocarcinoma.

High prevalence of ALD is linked to total alcohol intake (the risk sharply goes up when alcohol consumption increases from 25 to 100 g/day), the pattern of drinking (consuming more than 5 drinks/day over a long period of time and drinking without food), and gender of alcohol consumers (men are more resistant than women). However, alcohol-mediated liver damage is not entirely attributed to toxic effects of alcohol because only 10 to 15% of heavy drinkers actually develop ALD. In addition to alcohol-elicited toxic factors, the susceptibly to liver injury in heavy drinkers is based on multiple individual features, including genetic predisposition and comorbid conditions, such as viral hepatitis, diabetes, metabolic syndrome, etc.

The review articles presented in this issue, summarize the striking pathogenic features of ALD, which include the role of oxidative stress in induction of liver damage (reviewed by Defeng Wu and Arthur I. Cederbaum), alcohol-induced defects of methionine metabolism (reviewed by Kusum K. Kharbanda), and dysregulation of signaling pathways in parenchymal and nonparenchymal liver cells that provides the basis for altered immune responses (reviewed by Bharath Nath and Gyongyi Szabo). The main “driving force” of liver injury is based on the involvement of the secondary risk factors (“second hits”), which induce or speed up the progression of ALD in humans and in experimental models (reviewed by Hidekazu Tsukamoto, Keigo Machida, Alla Dynnyk, and Hasmik Mkrtchyan). One of the most clinically important examples of the “second hit” theory is the interactions between hepatitis C virus and alcohol, where alcohol consumption worsens the clinical course of hepatitis C by enhancing oxidative stress, viral replication, cytotoxicity, and impairment of immune functions (reviewed by Larry Siu, Julie Foont, and Jack R. Wands).

Several articles in this issue illustrate how the aforementioned mechanisms contribute to progression, clinical manifestations, and treatment of major ALD stages, which are steatosis, steatohepatitis (reviewed by Wing-Kin Syn, Vanessa Teaberry, Steve S. Choi, and Anna Mae Diehl), and liver fibrosis (reviewed by Francisco Javier Cubero, Raquel Urtasun, and Natalia Nieto). Finally, as a possible ALD outcome that affects mortality in alcoholic patients, liver cancer is also triggered by alcohol consumption (reviewed by Iain H. McKillop and Laura W. Schrum).

We believe that these “hot topic” reviews will be of great interest not only for clinicians, but also for all of those involved in alcohol research. The information provided in this issue, will further improve our understanding of modern molecular mechanisms of ALD pathobiology, along with their roles in the development of clinical manifestations of alcohol-induced liver damage and in reasonable therapeutic interventions.