Clinical significance of hepatitis B e antigen level measurement during long-term lamivudine therapy in chronic hepatitis B patients with e antigen positive.

Aim: To determine the changes of quantitative hepatitis B e antigen (HBeAg) that predicts early detection of non-response or breakthrough to long-term lamivudine (LAM) therapy.

Methods: Among HBeAg positive chronic hepatitis B patients who failed to achieve HBeAg seroconversion within 12 mo, we retrospectively analyzed 220 patients who had received LAM more than 24 mo.

Results: The mean duration of LAM therapy was 36 (range, 24-72) mo. HBeAg seroconversion after the first 12 mo of LAM therapy was achieved in 53 (24.1%) patients. Viral breakthrough was observed in 105 (47.7%) patients. To find out whether the changing patterns of HBeAg levels can predict the outcome of LAM therapy, we analyzed the reduction rates of HBeAg levels during LAM therapy. Using the decrease more than 90% of pretreatment HBeAg levels, the sensitivity and specificity of response were 96.2% and 70.1%, respectively. Patients were divided into 3 groups according to the reduction patterns of the decrease of quantitative HBeAg: decrescendo, decrescendo-crescendo, no change or fluctuating groups. The optimal time to predict non-response or breakthrough was the first 9 mo of therapy. At 9 mo of therapy, 49 (92.5%) of 53 patients who had achieved HBeAg seroconversion were included in the decrescendo group. On the contrary, in the no change or fluctuating group, only four (7.5%) had achieved HBeAg seroconversion. Among patients who did not show the continuous decrease of HBeAg levels at 9 mo, 95.2% (negative predictive value) failed to achieve HBeAg seroconversion.

Conclusion: Almost all patients who failed to show a continuous decrease of HBeAg levels at 9 mo of LAM therapy were non-response or breakthrough. Therefore, monitoring changes of HBeAg levels during LAM therapy in HBeAg positive chronic hepatitis B may be valuable for identifying patients who are at high risk of non-response or breakthrough.