富马酸替诺福韦二吡呋酯 vs. 恩曲他滨+富马酸替诺福韦二吡呋酯治疗拉米夫定耐药的慢性乙型肝炎患者的随机研究

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) is active against lamivudine-resistant hepatitis B virus (HBV) infection, but data to support its clinical efficacy in this setting are limited.

METHODS: In a prospective, double-blind, 96-week trial, patients were randomly assigned (1:1) to groups given TDF (300 mg, n=141) or a combination of emtricitabine (FTC, 200 mg; n=139) and TDF (300 mg, FTC+TDF). Patients were hepatitis B e antigen (HBeAg)-positive or HBeAg-negative, with levels of HBV DNA ≥3 log10 IU/mL and lamivudine resistance mutations (HBV polymerase or reverse transcriptase amino acid substitutions rtM204I/V±rtL180M by INNO-LiPA Multi-DR v3). The primary endpoint was proportion with HBV DNA <69 IU/mL (Roche COBAS Taqman assay).

RESULTS: Patient groups were well matched for demographic and disease characteristics, including region (60% from EU), HBV genotype (45% genotype D), HBeAg status (47% HBeAg-positive), and duration of lamivudine treatment (mean 3.8 y). At week 96 of treatment, 89.4% of patients in the TDF group and 86.3% in the FTC+TDF group had levels of HBV DNA <69 IU/mL (P=.43). HBeAg loss and seroconversion did not differ between groups; only 1 patient (0.7%) in the FTC+TDF group lost hepatitis B surface antigen. Treatment was well tolerated; confirmed renal events (creatinine increase of ≥0.5 mg/dL, creatinine clearance <50 mL/min, or level of PO4 <2 mg/dL) were generally mild and infrequent (<1%). Small reductions (<2%) in mean bone mineral density of hip and spine were detected by dual-energy X-ray absorptiometry in both groups. No TDF resistance developed through 96 weeks of treatment.

CONCLUSIONS: TDF alone is safe and effective for treatment of patients with lamivudine-resistant, chronic HBV infection.

结论：富马酸替诺福韦二吡呋酯单药治疗可有效应用于拉米夫定耐药的慢性乙型肝炎患者。