Lee Heon Ju, Kim Sang Jin, Kweon Young Oh, Park Soo Young, Heo Jeong, Woo Hyun Young, Hwang Jae Seok, Chung Woo Jin, Lee Chang Hyeong, Kim Byung Seok, Suh Jeong Ill, Tak Won Young, Jang Byoung Kuk
Department of Internal Medicine, Yeungnam University College of Medicine Daegu, South Korea.
Department of Internal Medicine, Keimyung University school of Medicine, Daegu, South Korea.
PLoS One. 2018 Jan 12;13(1):e0190581. doi: 10.1371/journal.pone.0190581. eCollection 2018.
The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear.
In this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96.
Patients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84-5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m2, p = 0.000).
Stable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function.
ClinicalTrials.gov NCT01732367.
对于拉米夫定（LAM）耐药的慢性乙型肝炎（CHB）患者且乙肝病毒（HBV）DNA检测不到，从LAM加阿德福韦酯（ADV）联合治疗转换为替诺福韦酯（TDF）单药治疗（稳定转换）的疗效尚不清楚。
在这项非劣效性试验中，LAM耐药的CHB患者在开始LAM+ADV联合治疗后血清HBV DNA检测不到（<20 IU/mL）超过6个月，被随机分组（1:2），要么继续联合治疗（LAM+ADV组，n = 58），要么转换为TDF单药治疗（TDF组，n = 111）。每12周进行血清生化检查和HBV DNA检测，随访96周。本研究的主要终点是第96周时病毒再激活患者的比例。
纳入本研究的CHB患者（n = 169）包括74例代偿期肝硬化患者。共有9例患者（LAM+ADV组4例，TDF组5例）退出研究。平均随访96周后，采用意向性分析，LAM+ADV组观察到的HBV再激活比例为6.8%（4/58），TDF组为4.5%（5/111）（差异为-2.3%；95%CI，-9.84 - 5.24%）。根据符合方案分析，两组均无受试者发生病毒再激活。未观察到严重不良反应。在治疗前后估计肾小球滤过率（eGFR）的亚组分析中，仅在有肝硬化的TDF组观察到eGFR下降（85.22对79.83 mL/min/1.73 m2，p = 0.000）。
对于LAM耐药的CHB患者且HBV DNA检测不到，与LAM+ADV联合治疗相比，稳定转换为TDF单药治疗在96周时产生非劣效结果。然而，肝硬化患者的TDF单药治疗需要密切关注肾功能。
ClinicalTrials.gov NCT01732367。
