Elsevier

Clinics in Liver Disease

Volume 16, Issue 4, November 2012, Pages 839-850
Clinics in Liver Disease

Liver Cancer and Alcohol

https://doi.org/10.1016/j.cld.2012.08.011Get rights and content

Introduction

Annually, HCC is diagnosed is approximately a half-million people worldwide, predominantly in Africa and Southeast Asia, where hepatitis B is widely prevelant.1, 2, 3 In the United States, approximately 7% of adults abuse alcohol, which is 5 times higher than the prevalence of hepatitis C.4 Based on the strong association of alcohol with cancer, an International Agency for Research on Cancer working group recently deemed alcoholic beverages “carcinogenic to humans,” being causally related to occurrence of malignant tumors of the oral cavity, pharynx, larynx, esophagus, liver, colorectum, and female breast.5, 6

Alcohol acts synergistically with pre-existing chronic liver disease, such as hepatitis C, hepatitis B, and fatty liver disease, as well as lifestyle choices, such as smoking and obesity, to further increase the risk of HCC in these disease states.

Alcohol promotes the generation of reactive oxygen species (ROS), which are highly reactive, oxygen-containing molecules that can damage cellular molecules, such as fats, proteins, or DNA. Alcohol metabolism in the liver leads to ROS production, induction of activity of cytochrome P450s, and reduction of antioxidants. ROS production and oxidative stress in hepatocytes play a crucial role in the development of alcoholic liver disease.7

This review attempts to analyze the epidemiology and pathogenesis of alcohol in HCC in both alcoholic liver disease and other chronic liver diseases where alcohol is a cofactor.

Section snippets

Data for Alcohol as Carcinogen

Chronic alcohol use of more than 80 g/d for longer than 10 years increases the risk for HCC by 5-fold.8 In a meta-analysis of alcohol drinking and cancer risk, increased trends in risk were observed for cancers of the liver (relative risk [RR] 1.86). Higher risks were found even for the lowest dose of alcohol (25 g/d) corresponding to approximately 2 drinks per day (Fig. 1).9

In an analysis of causes of 51,400 deaths from 1999 to 2006, in the United States, patients who died with a history of

Pathogenesis - alcohol as a carcinogen

The stomach absorbs 20% of alcohol, the rest absorbed by the duodenum and small intestine.46, 47 Alcohol dehydrogenase (ADH), located in the cytoplasm of hepatocytes, metabolizes the majority of alcohol.46, 47, 48, 49, 50, 51, 52 ADH-dependent alcohol metabolism results in oxidation of alcohol to acetaldehyde.46, 52 Acetaldehyde is further oxidized to acetate by the mitochondrial form of aldehyde dehydrogenase. The resulting acetate is then incorporated to form acetylcoenzyme A and oxidized in

Summary

Alcohol is a leading cause of liver cancer and alcohol abuse is 5 times more prevalent than chronic hepatitis C in the United States. Epidemiologic evidence supports that alcohol is an independent and strong risk factor for HCC. Quantification of the association is difficult, however, because cirrhosis and other liver conditions antedating the HCC diagnosis invariably lead to a substantial decrease in alcohol drinking. The annual incidence of HCC in patients with decompensated alcohol-induced

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