The study, reported in tomorrow's New England Journal of Medicine, followed almmost 11,900 Taiwanese men who had no initial signs of liver tumors.
When hepatitis B enters the body, fragments of the virus, called antigens, can be detected. If a person's blood has HBsAg antigens, they've been infected in the past with hepatitis B. If they have HBeAg fragments, the virus is still infecting their cells.
When the liver is infected with hepatitis, its cells undergo rapid turnover, dividing 100 to 1,000 times the normal rate to replace damaged tissue. This process may pave the way for cancerous gene mutations in the organ. It generally takes 20 to 30 years before the toll of hepatitis infection becomes cancer, says Dr. Bruce Bacon, a liver expert at St. Louis University.
Among the Taiwanese men, 111 developed hepatocellular carcinoma, the most common form of liver cancer, within about a decade.
In those with no hepatitis, there were 39 cases of liver cancer for every 100,000 person years. For those with HBsAg alone, that rose to 324 cases per 100,000 person years. However, for men with both HBsAg and HBeAg, the number jumped to 1,169 per 100,000 person years.
After accounting for other factors that increase the risk of liver cancer, including smoking, alcohol consumption and infection with hepatitis C, a history of hepatitis B infection upped the odds of cancer 9.6-fold and an active hepatitis B infection upped it 60-fold.
The researchers also conducted a smaller study in 130 men, and found hepatitis DNA was a strong predictor of liver cancer in men with HBsAG, but not HBeAg. However, they add, since DNA testing for the virus is expensive and requires special lab equipment, screening for HBeAg "may be a more practical way" of trying to estimate the risk of liver cancer.
Marc Ghany, of the National Institute of Diabetes and Digestive and Kidney Diseases, says the findings aren't surprising, since scientists have long known that hepatitis virus triggers liver cancer. However, the Taiwanese study is a smoking gun.
"Intuitively, we knew it, but there was not this sort of proof," says Ghany, co-author of an editorial accompanying the journal article.
Between 65 percent and 70 percent of people who contract hepatitis B have a form of the virus that spurs the production of HBeAg. The rest are infected with mutant strains that don't have that protein.
Yet, Ghany says, those people are still vulnerable to liver cancer if they have the mutant strains, which have become more prevalent and appear harder to treat.
An estimated 16,600 people in the United States will be diagnosed with liver cancer this year, and 14,100 will die of the disease, according to the American Cancer Society. Although relatively uncommon in the United States, liver cancer is one of the world's most prolific tumor killers.
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