Clin Mol Hepatol.  2014 Sep;20(3):267-273. 10.3350/cmh.2014.20.3.267.

Long-term outcomes of two rescue therapies in lamivudine-refractory patients with chronic hepatitis B: combined lamivudine and adefovir, and 1-mg entecavir

• Ze E
• Baek EK
• Lee JJ
• Chung HW
• Ahn DG
• Cho HJ
• Kwon JC
• Kim HJ
• Lee H

• KMID: 2069763
• DOI: http://doi.org/10.3350/cmh.2014.20.3.267

Abstract

BACKGROUND/AIMS
Adefovir (ADV) and lamivudine (LAM) combination therapy (ADV+LAM) has been a useful option for patients with LAM-resistant (LAM-r) chronic hepatitis B (CHB). However, the long-term outcomes of LAM+ADV and 1-mg entecavir (ETV) rescue therapies have still been limited. The aim of this study was to determine the long-term outcomes of these two rescue therapies.
METHODS
Sixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36) or 1-mg ETV (n=24). We determined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV) DNA by PCR (lower limitation of detection, < 140 copies/mL), biochemical response (alanine aminotransferase < 40 IU/mL), and the incidence of hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough.
RESULTS
Baseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56 months (range, 14-100 months) in the ADV+LAM group and 42 months (range, 12-73 months) in the ETV group (P=0.036). The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%, respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough and resistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P=0.001).
CONCLUSIONS
Combination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppression and resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time.

Keyword

Chronic hepatitis B; Lamivudine; Adefovir; Entecavir; Resistance

MeSH Terms

Adenine/*analogs & derivatives/therapeutic use
Adult
Aged
Alanine Transaminase/blood
Antiviral Agents/*therapeutic use
DNA, Viral/blood
Drug Resistance, Viral/genetics
Drug Therapy, Combination
Female
Genotype
Guanine/*analogs & derivatives/therapeutic use
Hepatitis B e Antigens/blood
Hepatitis B virus/genetics
Hepatitis B, Chronic/*drug therapy/virology
Humans
Lamivudine/*therapeutic use
Male
Middle Aged
Organophosphonates/*therapeutic use
Retrospective Studies
Treatment Outcome
Adenine
Alanine Transaminase
Antiviral Agents
DNA, Viral
Hepatitis B e Antigens
Guanine
Lamivudine
Organophosphonates