Yonsei Med J.  2017 May;58(3):552-556. 10.3349/ymj.2017.58.3.552.

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

• Kim DH
• Choi JW
• Seo JH
• Cho YS
• Won SY
• Park BK
• Jeon HH
• Shin SY
• Lee CK

• KMID: 2419112
• DOI: http://doi.org/10.3349/ymj.2017.58.3.552

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 reviews of the treatment effects of ETV-LdT switch therapy.

Keyword

Hepatitis B virus; entecavir; telbivudine

MeSH Terms

Adult
Alanine Transaminase/blood
Antiviral Agents/*therapeutic use
DNA, Viral/blood/genetics
Drug Resistance, Viral/genetics
Drug Substitution
Female
Follow-Up Studies
Guanine/*analogs & derivatives/therapeutic use
Hepatitis B virus/*drug effects/genetics/isolation & purification
Hepatitis B, Chronic/*drug therapy/*virology
Humans
Male
Middle Aged
Mutation
Polymerase Chain Reaction
Prospective Studies
Thymidine/*analogs & derivatives/therapeutic use
Treatment Outcome
Viral Load
Antiviral Agents
DNA, Viral
Guanine
Alanine Transaminase
Thymidine

Figure

• 

  Fig. 1 Study design and patient flow for both arms. A total of 60 patients with CHB were enrolled. Study population has been treated with 0.5 mg ETV for at least six months. A total of 60 patients were assigned randomly to ETV monotherapy continued group and LdT monotherapy switch group in 1:1 ratio. ETV, entecavir; HBV, hepatitis B virus; LdT, telbivudine; CHB, chronic hepatitis B; ALT, alanine aminotransferase; TDF, tenofovir.

• 

  Fig. 2 Detail of five patients in entecavir-telbivudine switching group with virological breakthrough. HBV, hepatitis B virus; TDF, tenofovir.

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