The profile and clinical significance of serum
hepatitis B surface antigen (
HBsAg) levels during long-term
nucleoside analogue (NA)
therapy in
chronic hepatitis B (CHB) is undetermined. From 1994 to 2002, 322 Chinese CHB patients were started on
lamivudine in our center. Patients were recruited if they were continuously treated with
lamivudine for at least 10 years and maintained favorable virologic responses throughout
therapy (HBV
DNA <2,000 IU/mL).
HBsAg and HBV
DNA levels were measured serially, and the predictability of
HBsAg kinetics in determining NA-related
HBsAg seroclearance was determined. Seventy patients were recruited, of which 43 (61.4%) were
hepatitis B e antigen (
HBeAg)-positive. Fifty-two (74.3%) patients had undetectable
viremia (HBV
DNA <20 IU/mL) during
therapy. Fifteen (21.4%) patients were followed up for 15 years. The median rate of
HBsAg reduction was 0.104 log IU/mL/year, with no significant difference found when comparing patients who were
HBeAg-positive versus
HBeAg-negative, were genotype B versus C, and had detectable versus undetectable
viremia during
therapy (all P > 0.05). Seven (10%) patients achieved
HBsAg seroclearance, and when compared with the remaining 63 patients, had significantly lower median baseline
HBsAg levels (P = 0.012) and a greater median rate of
HBsAg reduction (P < 0.001). Baseline
HBsAg levels and the rate of
HBsAg reduction achieved an area under the receiver operating characteristic curve of 0.860 (P = 0.004; 95% confidence interval [CI], 0.742-0.978) and 0.794 (P = 0.018; 95% CI, 0.608-0.979), respectively. Baseline
HBsAg <1,000 IU/mL and on-treatment reduction of
HBsAg >0.166 log IU/mL/year were optimal cutoff levels in predicting subsequent
HBsAg seroclearance (negative predictive values, 98.1% and 97.8%, respectively).
CONCLUSION: