Defining virologic relapse in chronic hepatitis B

Different definitions of virologic relapse (VR) are being used. One way of defining VR is "reappearance of HBV DNA in the serum," while another definition is an "increase in HBV DNA level greater than 1 log in two determinations at least 4 weeks apart." The aim of this study was to see the effectiveness of these two definitions

Forty-five HBeAg-positive chronic hepatitis B patients with a virologic response [negative PCR (<12 IU/ml)] who had discontinued therapy were analyzed retrospectively for VR, HBeAg reversion and biochemical flare.

HBV DNA reappeared in the serum (≥12 IU/ml) of all 45 patients (100%). An increase in HBV DNA level greater than 1 log in two determinations at least 4 weeks apart was identified in 20 of 25 patients (80%). Biochemical flare and HBeAg reversion were observed in 18 (40%) and 14 (31%) patients, respectively. Peak off-therapy HBV DNA level was significantly associated with biochemical flare (r=0.758, P<0.001) and HBeAg reversion (r=0.645, P<0.001). Two patients with high initial off-therapy HBV DNA levels (≥4.0 log(10) IU/ml) were reassessed at 4 weeks, and both experienced a biochemical flare and HBeAg reversion. Two patients had an increase in HBV DNA level greater than 1 log at a very low level (1 log to 2 or 3 log), but did not experience biochemical flare or HBeAg reversion during follow-up.

Reappearance of HBV DNA was universal when sensitive HBV DNA assay was used. Waiting 4 weeks to confirm VR may be harmful for patients with a high HBV DNA level, and was ineffective to indicate re-therapy for patients with increase in HBV DNA at a very low level. There is a need for improved and standardized definitions of VR.