Impact of serial hepatitis B virus DNA on hepatocellular carcinoma development in patients with liver cirrhosis

Objectives: We investigated the pattern of serial HBV DNA levels in known cirrhosis patients and its impact on the development of hepatocellular carcinoma (HCC). Methods: We analyzed a retrospective case/control study based on 352 HCC patients associated with HBV between 2005 and 2007. Prior to HCC development, 49 cirrhosis patients were tested for HBV DNA levels more than once a year (median 4 times) during the follow-up period. Ninety-eight consecutive cirrhosis patients without HCC, matched for age, sex and HBe Ag status were included as controls. Eighty-three patients in both groups had undergone antiviral therapy. Results: In cirrhosis, the most common HBV DNA pattern was fluctuating (33.3%), followed by persistently high (≥10⁴ copies/ml, 23.8%). Compared to a persistently low pattern (<10⁴ copies/ml), the relative risks of HCC in patients with persistently high and fluctuating patterns were 2.650 and 1.475. At multivariate analysis, a persistently high pattern was an independent risk factor for HCC (hazard ratio 3.135). Patients with sustained HBV DNA suppression during antiviral therapy were less likely to develop HCC than those with viral breakthrough/nonresponse. Conclusions: This study showed that persistent suppression of HBV DNA is also important to prevent the development of HCC in known cirrhosis patients.