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Among patients with chronic hepatitis B infection, risk of developing hepatocellular carcinoma (liver cancer) increases with increasing serum levels of hepatitis B virus DNA. These results were published in the Journal of the American Medical Association.

Hepatitis B is a virus that causes inflammation of the liver. It is spread through contact with body fluids and can be transmitted through blood, sexual contact, or from mother to infant during birth. While some individuals develop an acute infection and then recover, others develop a chronic infection. The probability of developing chronic hepatitis B is higher if the infection is acquired at a young age. Development of chronic hepatitis B increases a person’s risk for developing serious liver problems such as cirrhosis or hepatocellular carcinoma (HCC).[1]

Deoxyribonucleic acid (DNA) carries the genetic information of an organism. In patients with chronic hepatitis B, the amount hepatitis B virus DNA in the patient’s serum provides information about viral replication and the patient’s response to antiviral treatment. Suppression of viral DNA in the serum indicates a response to antiviral treatment.

In order to evaluate the relationship between the amount of viral DNA in a patient’s serum and the probability of developing HCC, researchers in Taiwan conducted a study among 3653 patients who were positive for hepatitis B virus and negative for hepatitis C virus (another type of hepatitis virus).[2] Study subjects were between the ages of 30 and 65 years. Because antiviral treatment for hepatitis B was not reimbursed by the national health insurance in Taiwan until fairly recently, none of the patients had received antiviral treatment.

During an average of 11 years of follow-up, researchers identified 164 new cases of HCC among study subjects. Patients with higher levels of hepatitis B virus DNA levels were more likely to develop HCC.

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  • Among patients with the lowest viral DNA levels, 1.3% of subjects developed HCC.
  • Among patients with the highest viral DNA levels, 15% developed HCC.

The relationship between viral DNA level and risk of HCC persisted after accounting for sex, age, smoking, alcohol consumption, HBeAg (a marker of hepatitis B virus replication), and serum level of alanine aminotransferase (elevated levels suggest liver damage). In fact, the relationship between viral DNA level and risk of liver cancer was particularly strong for patients who were negative for HBeAg and had normal serum levels of alanine aminotransferase.

The researchers conclude that patients with elevated serum levels of hepatitis B virus DNA are at increased risk of developing hepatocellular carcinoma. They recommend monitoring changes in serum hepatitis B virus DNA levels in patients with chronic hepatitis B. In addition, they recommend clinical trials to clarify the optimal treatment of patients who have elevated levels of hepatitis B virus DNA, but do not have evidence of liver damage or HBeAg.


[1] National Library of Medicine. Medical Encylopedia: Hepatitis B.(accessed January 6, 2006)

[2] Chen C-J, Yang H-I, Su J et al. Risk of Hepatocellular Carcinoma Across a Biological Gradient of Serum Hepatitis B Virus DNA Level. JAMA. 2006;295:65-73.