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Comparison of 208‐week sequential therapy with telbivudine and entecavir in HB eAg‐positive chronic hepatitis B patients with suboptimal responses to 24 weeks of Peg‐ IFN α‐2a therapy: An open‐labelled, randomized, controlled, “real‐life” trial
Author(s) -
Luo X. D.,
Chen X. F.,
Zhou Y.,
Chen X. P.
Publication year - 2017
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12790
Subject(s) - telbivudine , entecavir , medicine , gastroenterology , hbeag , adefovir , randomized controlled trial , hepatitis b , hepatitis b virus , chronic hepatitis , hbsag , immunology , lamivudine , virus
Summary The purpose of the study was to compare the efficacy and safety of 208‐week sequential therapy with telbivudine and entecavir in HB eAg‐positive chronic hepatitis B ( CHB ) patients with suboptimal responses to 24 weeks of Peg‐ IFN α‐2a therapy. This was an open‐label, randomized, controlled, “real‐life” trial. HB eAg‐positive CHB patients with serum HBV DNA ≥5.0 lg IU/mL and a < 1 lg IU/mL decline of HB sAg level from baseline who underwent at least 24 weeks of Peg‐ IFN α‐2a therapy were included. Enrolled patients were randomized to receive either telbivudine (600 mg/d, n = 95) or entecavir (0.5 mg/d, n = 95) for 208 consecutive weeks. Six patients were lost to follow‐up (4 patients in the telbivudine group and 2 in the entecavir group). Treatment was combined with adefovir when week 24 HBV DNA levels declined to <2 lg IU/mL versus baseline, when viral breakthrough occurred during treatment,or when HBV DNA remained detectable at 52 weeks ( HBV DNA ≥500 IU/mL). Responses and safety were assessed after 208 weeks of treatment. There were no significant differences among the baseline characteristics, including age, gender, and ALT , HBV DNA , HB sAg or HB eAg levels. After 208 weeks of treatment, there was no significant difference in the rates of undetectable HBV DNA ( HBV DNA <500 IU/mL) between the telbivudine group and the entecavir group (84/91,92.31% vs 88/93,94.62%, respectively, P = .525). More patients in the telbivudine group than the entecavir group achieved HB eAg clearance (74.73% vs 46.24%, respectively, P < .001) and HB eAg seroconversion (64.84% vs 38.71%, respectively, P < .001). Univariate analysis ( Enter , a = 0.05) of both groups showed that telbivudine, male gender and baseline HB eAg levels were significantly correlated with HB eAg seroconversion after 208 weeks of sequential therapy. Cox regression analysis ( Enter , a = 0.05) of the telbivudine group showed that the HB eAg seroconversion rate at 208 weeks was significantly correlated with gender (male) ( P = .006, HR =4.406), baseline HB eAg level ( P = .005, HR =0.433) and 24 w‐ HB eAg level reduction of more than 0.5 lg IU/ml from baseline ( P = .027, HR =0.487). All patients tolerated sequential telbivudine treatment; only slightly elevated creatine kinase levels were observed. Stratification analysis found that patients with baseline HB eAg levels less than 3 lg COI who switched to telbivudine may have had significantly improved HB eAg seroconversion rates. In conclusion, telbivudine promotes HB eAg seroconversion that merits investigation in HB eAg‐positive CHB patients with suboptimal responses to 24 weeks of Peg‐ IFN α‐2a therapy. We would suggest that patients with baseline HB eAg levels under 3 lg COI switch to telbivudine to achieve higher HB eAg seroconversion rates and use the early reductions in HB eAg levels (24 weeks) to guide treatment.