随访期间，4例患者有持续未检测出的HBV DNA，而6例患者的HBV DNA水平短暂上升，但没有人有GR。结论：在临床实践中，VBT在接受NUCs治疗的患者中很常见，但是近40%的VBTs与抗病毒药物的耐药性无关。询问CHB患者的用药依从性和对VBT/GR的确认可以避免不必要地更换抗病毒药物。
吉林大学第一医院肝胆胰内科 李蓥 摘译
本文首次发表于[Hepatology. 2011;53(6):1854-1863.]
Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice
Abstract
BACKGROUND AND AIMS: Virological breakthrough (VBT) is the first manifestation of antiviral drug resistance during nucleos(t)ide analogue (NUC) treatment of chronic hepatitis B (CHB), but not all VBTs are due to drug resistance.This study sought to determine the incidence of VBT and genotypic resistance (GR) in patients with CHB who were receiving NUCs in clinical practice.
METHODS: Records of patients with CHB who were receiving NUCs were reviewed. All patients with VBT were tested for drug resistance mutations.
RESULTS: Of 148 patients included, 73% were men and mean age was 44.9 years. During a mean follow-up of 37.5 ± 20.1 months, 39 (26%) patients had at least 1 VBT. Of these 39 patients, 15 (38%) were not confirmed to have VBT on retesting, and 10 of these 15 had no evidence of GR. The cumulative probability of VBT, confirmed VBT, and GR at 5 years was 46.1%, 29.7%, and 33.9%, respectively. In multivariate analysis, failure to achieve undetectable hepatitis B virus (HBV) DNA was the only factor significantly associated with VBT. Among the 10 patients who had VBT but no confirmed VBT or GR and who were maintained on the same medications, serum HBV DNA decreased in all 10, and 9 had undetectable HBV DNA at a mean of 6.8 months after the VBT. Four patients had persistently undetectable HBV DNA, six had transient increase in HBV DNA during follow-up, and none had GR.
CONCLUSIONS: VBT was common in patients with CHB receiving NUCs in clinical practice, but nearly 40% of the VBTs were not related to antiviral drug resistance. Counseling of patients with CHB on medication adherence and confirmation of VBT and/or GR can avoid unnecessary changes in antiviral medications.
