Nanfang Hospital, Southern Medical University, Guangzhou, China.
School of Medicine, Ruijin Hospital Affiliated to Jiaotong University, Shanghai, China.
J Gastroenterol Hepatol. 2022 Mar;37(3):471-479. doi: 10.1111/jgh.15757. Epub 2022 Jan 6.
Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B virus (HBV) infection for its high potency and a low rate of drug resistance. This study investigated the efficacy and safety of TDF in Chinese patients with chronic hepatitis B (CHB) infection after treatment failure with multiple nucleos(t)ide analogues (NAs).
Patients included were aged 18-65 years, with treatment failure with multiple NAs (serum HBV DNA > 200 IU/mL after more than two different NA treatments). The primary endpoint was proportion of patients with serum HBV DNA < 20 IU/mL at Week 144 of TDF monotherapy. Secondary endpoints and safety were also assessed.
Overall, 213 patients were enrolled. At Week 144, mean HBV DNA decreased significantly from baseline (4.4 vs 1.4 log IU/mL), with 77.0% patients (95% confidence interval: 71.1, 82.9) achieving serum HBV DNA < 20 IU/mL. Three (1.4%) patients experienced virological breakthrough during TDF monotherapy, without hepatitis flare. At Week 144, 15.3% and 4.7% patients (hepatitis B e antigen [HBeAg]-positive at baseline) experienced HBeAg loss and HBeAg seroconversion, respectively; 68.3% patients achieved normalized alanine aminotransferase levels. Overall, 58.7% patients experienced more than one adverse event (AE). Most common AEs were upper respiratory tract infection and blood creatine phosphokinase increase; 8.5% patients experienced study drug-related AEs; 9.4% patients experienced serious AEs (none were TDF-related). Among renal safety parameters, overall trend of mean serum phosphorous level remained stable, while mean estimated glomerular filtration rate increased slightly.
Tenofovir disoproxil fumarate monotherapy is efficacious in CHB patients with multiple NAs treatment failure with no new safety findings.
富马酸替诺福韦二吡呋酯（TDF）是慢性乙型肝炎病毒（HBV）感染的一线治疗药物，因为它具有高效力和低耐药率。本研究调查了 TDF 在多重核苷（酸）类似物（NA）治疗失败的慢性乙型肝炎（CHB）患者中的疗效和安全性。
纳入的患者年龄为 18-65 岁，多重 NA（两种以上不同 NA 治疗后血清 HBV DNA>200IU/mL）治疗失败。主要终点是 TDF 单药治疗 144 周时血清 HBV DNA<20IU/mL 的患者比例。还评估了次要终点和安全性。
共有 213 例患者入组。在 144 周时，HBV DNA 从基线显著下降（4.4 对 1.4log IU/mL），77.0%（95%置信区间：71.1，82.9）的患者达到血清 HBV DNA<20IU/mL。3（1.4%）例患者在 TDF 单药治疗期间发生病毒学突破，无肝炎发作。在 144 周时，15.3%和 4.7%（基线时 HBeAg 阳性）的患者分别发生 HBeAg 丢失和 HBeAg 血清学转换；68.3%的患者达到正常丙氨酸氨基转移酶水平。总体而言，58.7%的患者发生了超过一次不良事件（AE）。最常见的 AE 是上呼吸道感染和血肌酸磷酸激酶升高；8.5%的患者发生与研究药物相关的 AE；9.4%的患者发生严重 AE（均与 TDF 无关）。在肾安全参数方面，血清磷平均水平的总体趋势保持稳定，而估算肾小球滤过率略有增加。
TDF 单药治疗多重 NA 治疗失败的 CHB 患者有效，无新的安全性发现。
