Yuan Gui-Cai, Chen Ai-Zhen, Wang Wei-Xin, Yi Xu-Lan, Tu Long, Peng Fang, Qiu Zhi-Hong
Department of Infectious Diseases, Yichun University Second Affiliated Hospital, Yichun 336000, Jiangxi Province, China.
World J Clin Cases. 2023 Dec 6;11(34):8139-8146. doi: 10.12998/wjcc.v11.i34.8139.
Entecavir (ETV) is a potent and safe antiviral agent for patients with chronic hepatitis B (CHB); however, some patients may exhibit suboptimal response or resistance to ETV. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate.
To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV.
A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia [Hepatitis B virus (HBV) DNA ≥ 20 IU/mL] or partial virologic response (HBV DNA < 20 IU/mL, but detectable) were enrolled in the study. The patients were randomly assigned to either continue ETV (0.5 mg) daily or switch to TAF (25 mg) daily for 48 wk. The primary endpoint was the proportion of patients who achieved a virologic response (HBV DNA level < 20 IU/mL) at week 48. Secondary endpoints included changes in serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-HBe levels, and renal and bone safety parameters.
At week 48, the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group (93.3% 66.7%, = 0.012). The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group (-3.8 -2.4 Log10 IU/mL, < 0.001). The rates of ALT normalization, HBeAg loss, HBeAg seroconversion, and HBsAg loss were not found to significantly differ between the two groups. None of the patients developed genotypic resistance to ETV or TAF. Both drugs were well tolerated, with no serious adverse events or discontinuations caused by adverse events. No significant changes were observed in the estimated glomerular filtration rate, serum creatinine level, or urine protein-to-creatinine ratio in either group. The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group (-0.8% -2.1%, = 0.004; -0.6% -1.8%, = 0.007, respectively).
Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.
恩替卡韦（ETV）是一种用于慢性乙型肝炎（CHB）患者的强效且安全的抗病毒药物；然而，一些患者可能对ETV表现出欠佳的反应或耐药性。替诺福韦艾拉酚胺（TAF）是一种新型替诺福韦前体药物，与富马酸替诺福韦二吡呋酯相比，其药代动力学有所改善，肾脏和骨骼毒性降低。
评估在对ETV反应欠佳的CHB患者中从ETV转换为TAF的疗效和安全性。
总共60例接受ETV治疗至少12个月且有持续性或复发性病毒血症[乙型肝炎病毒（HBV）DNA≥20 IU/mL]或部分病毒学应答（HBV DNA<20 IU/mL，但可检测到）的CHB患者纳入本研究。患者被随机分配为继续每日服用ETV（0.5 mg）或转换为每日服用TAF（25 mg），持续48周。主要终点是在第48周达到病毒学应答（HBV DNA水平<20 IU/mL）的患者比例。次要终点包括血清丙氨酸氨基转移酶（ALT）、乙型肝炎表面抗原（HBsAg）、乙型肝炎e抗原（HBeAg）和抗-HBe水平的变化，以及肾脏和骨骼安全性参数。
在第48周时，TAF组达到病毒学应答的患者比例显著高于ETV组（93.3%对66.7%，P=0.012）。TAF组从基线开始的HBV DNA平均下降幅度也显著大于ETV组（-3.8对-2.4 Log10 IU/mL，P<0.001）。两组间ALT正常化率、HBeAg消失率、HBeAg血清学转换率和HBsAg消失率未发现有显著差异。没有患者对ETV或TAF产生基因型耐药。两种药物耐受性良好, 没有严重不良事件或因不良事件导致停药。两组的估计肾小球滤过率、血清肌酐水平或尿蛋白与肌酐比值均未观察到显著变化。TAF组腰椎和髋部的骨密度下降幅度显著低于ETV组（分别为-0.8%对-2.1%，P=0.004；-0.6%对-1.8%，P=0.007）。
对于对ETV反应欠佳的CHB患者，从ETV转换为TAF是有效且安全的，可能预防进一步的病毒耐药并降低肾脏和骨骼毒性。
