From Seminars in Liver Disease
Iain H. McKillop, Ph.D.; Laura W. Schrum, Ph.D.
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and contributes significantly to cancer-related morbidity and mortality. Chronic alcohol consumption has long been associated with progressive liver disease toward the development of hepatic cirrhosis and the subsequent increased risk for developing HCC. In assessing the role of alcohol during hepatic disease, and as a carcinogen, many of the deleterious effects of alcohol can be attributed to alcohol metabolism in hepatocytes. In addition to the direct effects of alcohol/alcohol metabolism on hepatocyte transformation, increasing evidence indicates that other intrahepatic and systemic effects of alcohol are likely to play an equally significant role in the process of hepatic tumorigenesis.
Introduction
Primary tumors of the liver represent the fifth most common type of cancer in the world and the third leading cause of cancer-related death.[1-3] Current estimates indicate that 500,000 to 1,000,000 new cases are diagnosed each year.[2-5] Of all primary tumors arising in the liver, ~80% are hepatocellular carcinomas (HCCs) that occur following transformation of cells of the hepatic parenchyma (hepatocytes).[1,6-8] Unlike many other common malignancies, HCC is unusual in that common familial patterns of development rarely exist. Rather, the incidence of HCC strongly correlates with exposure to one or more known risk factors, of which viral hepatitis infection, aflatoxin ingestion, and/or prolonged heavy alcohol consumption are the most common.[1,7,9-11] Each of these factors is considered significant for the development of underlying hepatic disease and progression to HCC, and in combination the effects are synergistic.[8,12-16]
The nature of these risk factors is such that distinct geographical patterns of HCC incidence exist.[2,3,6,16] The majority of HCC occur in countries located in Eastern Asia or sub-Saharan Africa. These countries exhibit the highest incidence of hepatitis B (HBV) and C (HCV) virus infection and risk of exposure to aflatoxins (naturally occurring mycotoxins from the Aspergillus species of fungi that typically colonize poorly stored grain, especially in regions of high humidity[16]). In these regions, the incidence of HCC is typically 20 to 50/100,000 and has been reported as high as 95.7/100,000 in regions of China.[3,4] In North America and Northern Europe, HCC has traditionally been considered a relatively rare cancer with an incidence rate of 1 to 2.5/100,000. Despite increases in HCC in the United States over the past two decades (due to increased HCV infection) alcohol-associated risk for HCC development is still considered the major risk factor.[9,17-20] In addition to the correlation with exposure to risk factors, demographic factors, such as age, sex, and ethnicity, have also been reported to influence susceptibility to HCC development.[2-4,7]
Regardless of the underlying etiology of HCC, the prognosis for those diagnosed is uniformly bleak; the annual number of estimated HCC-related deaths only marginally lagging behind that of new cases diagnosed.[4,7,21,22] At present, the best available treatments for HCC remain resection or ablation of the tumor mass or complete hepatic transplant.[22-28] However, the insidious nature of HCC coupled with the absence of reliable, early disease markers often leads to late detection, which, coupled with the underlying pathophysiology, limits the therapeutic options available.[15,22,24,29-31] Similarly, although complete liver transplant represents an alternative to resection, a lack of transplantable organs, underlying pathophysiology, and the incidence of metastases often limits this option.[27,30,32]
http://www.medscape.com/viewarticle/705411?src=mp&spon=17&uac=71630FV
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