European Journal of Gastroenterology & Hepatology:
July 2013 - Volume 25 - Issue 7 - p 814-819
doi: 10.1097/MEG.0b013e32835ee516
Original Articles: Hepatitis
替比夫定联合阿德福韦治疗慢性乙型肝炎患者
病毒学突破或基因型耐药，替比夫定
Telbivudine plus adefovir therapy for chronic hepatitis B patients with
virological breakthrough or genotypic resistance to telbivudine
Background/aim: There is very limited experience in the management of
telbivudine (LdT)-associated virological breakthrough (VBT) and resistance
in the treatment of chronic hepatitis B (CHB) patients, and the guideline
recommendations are primitively based on the general principles of rescue
therapy to nucleos(t)ide analog resistance. The aim of this study is to
determine the effect of the addition of adefovir (ADV) in hepatitis B e
antigen (HBeAg)-positive CHB patients with VBT or resistance to LdT.
Methods: Thirty-seven CHB patients with confirmed VBT and 31 patients with
genotypic resistance to LdT were enrolled and thereafter treated with a
combination of LdT and ADV for 12 months.
Results: Combination therapy was
safe and the majority of patients tolerated the therapy. LdT+ADV led to
rapid decreases in viral loads, and viral replications were persistently
suppressed, with 2.17 (VBT) and 2.31 (resistance) log10 copies/ml
reductions 12 months after rescue therapy, respectively. The rates
corresponding to virological and biochemical responses were similar between
the two groups at the end of observations (70.3 vs. 74.2% for virological
response, P=0.720; 64.0 vs. 65.5% for biochemical response, P=0.907). The
cumulative rates of serological responses were higher in patients with VBT
than in those with resistance (35.1 vs. 9.67% for HBeAg loss, P=0.014; 10.8
vs. 3.23% for HBeAg/anti-HBe seroconversion, P=0.233).
Conclusion: LdT and
ADV combination therapy led to significant decreases in serum hepatitis B
virus DNA levels and normalization of alanine aminotransferase levels in
patients with VBT or genotypic resistance to LdT. This rescue strategy was
also associated with a higher rate of HBeAg serological outcomes in
patients with confirmed LdT-related VBT.