THE ANALYSIS OF EFFICACY OF TENOFOVIR BASED-RESCUE THERAPY IN CHRONIC HEPATITIS B PATIENTS ACCORDING TO GENOTYPIC RESISTANT MUTATION TO NUCLEOS(T)IDE ANALOGUES

초록

Background and Aims: Clinical data for the efficacy of TDF in ADF-R (resistance) and entecavir (ETV)-R is still limited. We aim to investigate the efficacy and its influencing factors of TDF rescue therapy according to genotypic resistant mutation to nucleos(t)ide analogues. Methods: This study included 152 patients who had documented genotypic resistance mutations to lamivudine (LAM), ADV or ETV and HBV DNA > 20 IU/mL before receiving TDF-based rescue therapy more than 12 months. Virologic response (VR) were defined as HBV DNA < 12 IU/mL. Results: Median duration of treatment was 20.9 months and 66 (43.4%) received TDF based combination therapy. Baseline mean HBV DNA was 3.11 ± 1.5 log10 IU/mL. The number of patients with LAM/ADV/ETV mutation are 125 (82%)/51 (34%)/32 (21%), respectively. The overall cumulative probability of achieving VR was 85.5% and 88.1% at 12 and 24months. There were 2 VBT (1 in TDF monotherapy and 1 in combination therapy) and no novel genotypic resistance mutation was not detected. There was no difference of VR between with or without mutation of LAM ( p = 0.07) or ETV ( p = 0.79), respectively. Interestingly, patients with ADV-R achieved significantly lower VR than without (72.5% vs. 96.0%, p < 0.01). The patients with A181T (91.3% vs. 77.7%, p < 0.01) or A181V (90.1% vs. 75.0%, p = 0.04) achieved lower VR than without. But, the presence of N236T ( p = 0.87) or A181T/V + N236T (0.75) did not decrease VR. Nevertheless, VR was not different between the TDF monotherapy and TDF combination therapy in patients with ADV-R ( p = 0.19). In multivariate analysis to detect influencing factors for VR, presence of ADV-R [OR 0.659, 95% CI: 0.440–0.987, p = 0.04] and higher baseline HBV DNA levels [OR 0.607, 95% CI: 0.420–0.878, p < 0.01] were significantly associated with decreased VR rate. In subgroup analysis for patients with ADV_R, there was no difference of VR between patients with respective mutation of ADV_R. Higher baseline HBV DNA levels [OR 0.42, 95% CI: 0.19–0.89, p < 0.01] was only significant factor for lower VR rate. Conclusions: TDF monotherapy provided a virologic response comparable to that of combination therapy in patients with documented genotypic resistant mutation to nucleos(t)ide analogues. However, TDF based therapy showed limited efficacy to ADV-R mutation compared to other mutation of nucleoside analogues, especially A181T/V. Further study is needed to evaluate long-term efficacy of TDF based therapy for CHB patients with ADV-R.