Chen C-J et al. (2006) Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 295: 65–73

Chronic hepatitis B virus (HBV) infection is a risk factor for developing hepatocellular carcinoma. The concentration of HBV DNA in the serum of infected patients (viral load) is used to guide antiviral therapy and can be measured by polymerase chain reaction. Chen and colleagues investigated whether serum HBV viral load could predict progression to hepatocellular carcinoma.

In this prospective cohort study, the incidence of hepatocellular carcinoma and the HBV viral load were assessed at baseline and in follow-up examinations (mean follow-up 11.4 years) in patients seropositive for the HBV surface antigen (n = 3,653). The investigators identified 164 hepatocellular carcinoma cases; the incidence rate per 100,000 patient-years increased from 108.3 in patients with undetectable viral load (<300 copies/ml) to 1,152.0 for patients with high viral load (>1 × 106 copies/ml). After adjusting for confounders such as liver cirrhosis and serum alanine aminotransferase level, the risk of hepatocellular carcinoma was significantly higher in those with high viral load at baseline than in those with low viral load (biological gradient P <0.001). The risk of developing hepatocellular carcinoma was greatest for patients who had persistently elevated HBV viral load.

The authors conclude that elevated HBV viral load is a major risk factor for the development of hepatocellular carcinoma; measurement of a patient's HBV viral load should be used to guide antiviral therapy. Future trials should compare different treatment strategies in patients with high levels of HBV DNA.