Abstract
Objective: To investigate the optimal treatment regimen for patients with HBeAg-positive chronic hepatitis B (CHB) after suboptimal response to 24 weeks of pegylated interferon (Peg-IFN) α-2a. Methods: A total of 188 patients with HBeAg-positive CHB who had suboptimal response to 24 weeks of Peg-IFN α-2a were randomly divided into entecavir group (n = 93) and telbivudine group (n = 95). The two groups received entecavir 0.5 mg/d and telbivudine 0.6 g/d, respectively, for 208 weeks. After 208 weeks of treatment, the following indices were assessed: HBeAg clearance rate and seroconversion rate, hepatitis B virus (HBV) DNA clearance rate (HBV DNA < 500 IU/ml), safety, and drug resistance rate. The data were subjected to intention-to-treat (ITT) analysis and per protocol (PP) analysis. Univariate and multivariate logistic regression analyses were performed for the drugs used and baseline characteristics in patients with or without HBeAg seroconversion, and stratification analysis was performed based on the baseline HBeAg level. Results: Six cases in the entecavir group and four cases in the telbivudine group did not complete the treatment. Sequential entecavir and telbivudine were well tolerated and safe for all patients. There was a significant difference in HBV DNA clearance rate at 52 weeks of treatment between the entecavir group and the telbivudine group (ITT analysis: 93.55% [87/93] vs 77.89% [74/95], χ (2) = 9.363, P = 0.002; PP analysis: 93.10% [81/87] vs 76.92% [70/91], χ (2) = 9.049, P = 0.003). The suppression rates of HBV DNA at 208 weeks of treatment were 95.70% (89/93) vs 92.63% (88/95) (ITT analysis) and 95.40% (83/87) vs 92.31% (84/91) (PP analysis). There was a significant difference in HBeAg seroconversion rate at 208 weeks of treatment between the entecavir group and the telbivudine group (ITT analysis: 38.71% [36/93] vs 62.11% [59/95], χ (2) = 10.290, P = 0.001; PP analysis: 41.38% [36/87] vs 64.84% [59/91], χ (2) = 9.833, P = 0.002). Univariate and multivariate logistic regression analyses suggested that sequential use of telbivudine, male sex, and the baseline level of HBeAg were significantly associated with HBeAg seroconversion at 208 weeks of treatment (P = 0.003, hazard ratio [HR] = 0.386; P = 0.009, HR = 0.303; P = 0.001, HR = 3.502). Conclusion: For patients with HBeAg-positive CHB after suboptimal response to 24 weeks of Peg-IFNα-2a, sequential use of telbivudine is the optimal treatment regimen according to the baseline level of HBeAg (baseline guidance). The incidence of HBeAg seroconversion during 208 weeks of sequential treatment can be significantly increased according to the HBeAg decline curve in early treatment (24 weeks) and 104 weeks (response guidance).