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Liver Cancer (cont.)

Causes of Primary Liver Cancer

Most people who develop hepatoma have a liver that has already been damaged in some way, usually many years earlier. The most common risk factor in the United States is alcohol abuse; in the rest of the world, hepatitis B and hepatitis C are the risk factors responsible for most cases of hepatoma. Although these are preventable problems, the incidence of hepatoma is actually rising in many countries. In the United States, due in part to a large increase in hepatitis C infection several decades ago, the incidence has doubled to over 17,000 cases each year. Recent research has demonstrated that a large part of the increase in hepatoma is due to the rise in obesity and diabetes over the past few decades. Certain genetic diseases, such as hemochromatosis (a disease that results in abnormally high stored levels of iron), can also eventually result in the development of this tumor, as can aflatoxin, a food contaminant that is common in Africa and Southeast Asia.

Alcohol abuse: Those with a history of alcohol abuse have about a 15% lifetime chance of developing hepatoma, and it is frequently found unexpectedly at autopsy in alcoholics who die from other causes. The risk rises with increasing alcohol use but only up to a certain point; severe alcoholics will not live long enough to develop the cancer, and because of this, the risk actually rises after quitting drinking.

Hepatitis B: This DNA virus is the most common cause of hepatocellular cancer worldwide, responsible for most cases of hepatoma in geographic areas where it is a very common cancer (Asia and sub-Saharan Africa). Many people in these parts of the world get infected with the virus at a young age, and 15% are unable to clear the virus from their systems. This leads them to become "chronic carriers," which increases the risk of developing hepatoma 200 times higher than normal. Along with steady and repeated destruction of the liver cells, the virus transfers some of its DNA into the human liver cells, and this helps initiate the process of transforming to a cancer cell (carcinogenesis).

Hepatitis C: This is an RNA virus, causing millions of infections over the past few decades by contaminated needles or blood products before a screening test was developed. This infection is responsible now for about three-quarters of all hepatomas in Japan and Europe. After infection, there is a lifetime risk of 5% of developing hepatoma, at an average time of 28 years after infection.

Aflatoxin: This is a byproduct of a mold affecting spoiled stored food products such as grains and peanuts in parts of the world such as Africa, Thailand, and the Philippines. Aflatoxin binds to the DNA of live cells and causes mutations that lead to cancer. This was the first discovery of precisely how an environmental contaminant causes cancer to develop on the molecular level. There is no significant amount in any food for humans in the United States (although there has been contamination of feed for cattle that eventually showed up in small amounts in their milk).

NASH: Diabetes and obesity lead to the development of a condition known as fatty liver and non-alcoholic steatorrheic hepatitis (NASH). This causes the accumulation of fatty acids within the liver cells that eventually cause liver damage. Over a 10-year period, this more than triples the risk of hepatoma and makes it much more likely that the cancer will return after surgery.

What most of these processes have in common is that they lead to cirrhosis, which is a severe and irreversible scarring disease of the liver that leads to repeated cycles of cell death and regeneration, eventually allowing some of these cells to become cancerous. In the United States, about one-quarter of people with hepatoma have no risk factors at all, and no reason can be found.

Medically Reviewed by a Doctor on 2/19/2013

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