Entecavir to Telbivudine Switch Therapy in Entecavir-Treated Patients with Undetectable Hepatitis B Viral DNA

다국어 초록 (Multilingual Abstract)

Purpose: This study examined 2-year outcome of consecutive therapy using entecavir (ETV) followed by telbivudine (LdT) in subjects with undetectable hepatitis B virus (HBV) DNA level and normal alanine aminotransferase level after the initial 6 months of ETV treatment.
Materials and Methods: Sixty subjects were randomized to continue with ETV or switch to LdT. Significant difference in baseline characteristics was not found between the two groups. Persistent HBV DNA level of 20–60 IU/mL in three consecutive samples collected three months apart or singly measured HBV DNA level of >60 IU/mL was defined as virological rebound.
Results: During 96 weeks of follow-up, all subjects of the ETV-only group (n=30) resulted in undetectable HBV DNA level. On the other hand, 83.3% (n=25) of the LdT-switched group showed treatment success. Virological rebound time varied from week 24 to 84 after switching to LdT. HBV DNA level was 180 to 2940 IU/mL at rebound time. All subjects with virological rebound (n=5) showed drug-resistant mutation: three had mutation rtM204I, and two had mutation rtM204V. Consecutive treatment using ETV followed by LdT showed virological rebound in 16.7% of subjects during 96 weeks of follow-up. HBV DNA negativity during initial ETV therapy could not be achieved in patients who switched to LdT.
Conclusion: Consecutive treatment using ETV followed by lamivudine was ineffective for treating chronic hepatitis B. LdT was found as a more potent antiviral agent than lamivudine. However, this conclusion requires larger-scale, long-term prospective reviewsof the treatment effects of ETV-LdT switch therapy.

참고문헌 (Reference)

1 Lai CL, "Telbivudine versus lamivudine in patients with chronic hepatitis B" 357 : 2576-2588, 2007

2 Leemans WF, "Switching patients with lamivudine resistant chronic hepatitis B virus from tenofovir to adefovir results in less potent HBV-DNA suppression" 15 : 108-114, 2008

3 Shi M, "Sequential treatment with lamivudine and interferon-alpha monotherapies in hepatitis B e antigen-negative Chinese patients and its suppression of lamivudine-resistant mutations" 58 : 1031-1035, 2006

4 Niro GA, "Sequential treatment with lamivudine and alpha-interferon in anti-HBe-positive chronic hepatitis B patients: a pilot study" 39 : 857-863, 2007

5 Lee JM, "Rescue monotherapy in lamivudine-resistant hepatitis B e antigen-positive chronic hepatitis B: adefovir versus entecavir" 14 : 705-712, 2009

6 Fung J, "Randomized trial of lamivudine versus entecavir in entecavir-treated patients with undetectable hepatitis B virus DNA: outcome at 2Years" 53 : 1148-1153, 2011

7 Lampertico P, "Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients" 133 : 1445-1451, 2007

8 Lee HW, "Lamivudine maintenance beyond one year after HBeAg seroconversion is a major factor for sustained virologic response in HBeAgpositive chronic hepatitis B" 51 : 415-421, 2010

9 Lee WM, "Hepatitis B virus infection" 337 : 1733-1745, 1997

10 Yuen MF, "Hepatitis B virus DNA levels at week 4 of lamivudine treatment predict the 5-year ideal response" 46 : 1695-1703, 2007

11 Pol S, "First-line treatment of chronic hepatitis B with entecavir or tenofovir in ‘real-life’ settings: from clinical trials to clinical practice" 19 : 377-386, 2012

12 Yuen MF, "Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy" 34 (34): 785-791, 2001

13 Sherman M, "Entecavir for treatment of lamivudine-refractory, HBeAgpositive chronic hepatitis B" 130 : 2039-2049, 2006

14 Lui YY, "Cost-effectiveness analysis of roadmap models in chronic hepatitis B using tenofovir as the rescue therapy" 15 : 145-155, 2010

15 Zeuzem S, "Baseline characteristics and early on-treatment response predict the outcomes of 2 years of telbivudine treatment of chronic hepatitis B" 51 : 11-20, 2009

16 Seo YS, "Antiviral efficacy of adefovir dipivoxil versus lamivudine in patients with chronic hepatitis B sequentially treated with lamivudine and adefovir due to lamivudine resistance" 13 : 4072-4079, 2007

17 Fung J, "Adefovir dipivoxil monotherapy and combination therapy with lamivudine for the treatment of chronic hepatitis B in an Asian population" 12 : 41-46, 2007

18 Lai CL, "A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B" 129 : 528-536, 2005

19 Liaw YF, "2-year GLOBE trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B" 136 : 486-495, 2009