Stringent cessation criterion results in better durability of lamivudine treatment: a prospective clinical study in hepatitis B e antigen‐positive chronic hepatitis B patients

Summary. The cessation criteria for lamivudine treatment vary in published articles and their results are contradictory, especially factors predicting relapse. To clarify these contradictions, this long‐term follow‐up study of 125 Chinese hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients was designed with stringent cessation criterion. All patients received lamivudine and achieved HBeAg seroconversion (group A, n = 82) or loss (group B, n = 43) with undetectable hepatitis B virus (HBV) DNA by PCR assay during the treatment. Lamivudine was withdrawn ≥6 months after HBeAg seroconversion/loss occurred. The median treatment durations were 24 (12–54) months and 36 (18–89) months in group A and group B, respectively. Patients were followed up for median 24 (2–84) months. The cumulative relapse (defined as serum HBV DNA ≥10⁴ copies/mL) rates in the two groups at months 12, 24, 36 and 48 were 23.4%vs 35.0%, 25.0%vs 37.7%, 25.0%vs 41.1% and 29.4%vs 41.1%, respectively (log‐rank test, P = 0.119). For patients whose total treatment duration ≥18 months in group A, the cumulative relapse rates at months 12, 24, 36 and 48 were 18.3%, 20.1%, 20.1% and 25.1%, which was significantly lower than those with a shorter duration (log‐rank test, P = 0.002). The mean age and median total duration were statistically different between relapsers and nonrelapsers in group A (33.9 ± 13.6 vs 23.1 ± 11.0 years, P < 0.001 and 24 vs 26 months, P = 0.003). Cox regression revealed that age was the only predictive factor for relapse (RR, 1.069; 95% CI, 1.032–1.106, P < 0.001). Patients aged <30 years relapsed less frequently in 5 years (12.3%vs 53.5%, P = 0.001). In conclusion, for patients who maintained HBeAg seroconversion for ≥6 months and total duration for ≥18 months, lamivudine withdrawal is a reasonable option. Prolonged treatment may be required for patients aged greater than 30 years to reduce relapse.