State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
3rd Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Hepatol Int. 2019 May;13(3):260-269. doi: 10.1007/s12072-019-09943-6. Epub 2019 Apr 11.
Long-term treatment with tenofovir disoproxil fumarate (TDF) has demonstrated suppression of viral replication outside of China. This study aims to assess efficacy, resistance and safety of TDF for up to 240 weeks in Chinese patients with chronic hepatitis B virus (HBV) infection.
Patients (HBeAg-positive or HBeAg-negative) who were randomised to receive TDF 300 mg or adefovir dipivoxil (ADV) 10 mg once daily in the 48-week double-blind phase (N = 498) were eligible to enter the open-label TDF phase (TDF-TDF and ADV-TDF groups) for additional 192 weeks.
Overall, 457/512 (89.3%) randomised patients completed 240 weeks of treatment. Virological suppression was achieved in 84.5% and 87.9% in HBeAg-positive patients and 89.6% and 89.5% in HBeAg-negative patients in TDF-TDF and ADV-TDF groups, respectively, at week 240. The majority of patients from both groups had normalized alanine transaminase levels. More patients had HBeAg loss (41.7% vs. 36.4%) and HBeAg seroconversion (32.0% vs. 28.3%) in TDF-TDF than in ADV-TDF group, respectively. Only one HBeAg-positive patient in TDF-TDF group had HBsAg loss at week 240. No evidence of resistance to TDF was observed. The incidence of adverse events was similar in both groups (TDF-TDF, 56.4% vs. ADV-TDF, 51.6%). One patient had serum creatinine elevation ≥ 0.5 mg/dL above baseline, and three patients had confirmed grade 3/4 phosphorus abnormalities (< 2 mg/dL).
In Chinese patients with chronic HBV, long-term treatment with TDF showed sustained viral suppression without development of resistance up to 240 weeks. No new safety concerns were found with TDF in this patient population. Clinical Trial Registration ClinicalTrial.gov Identifier NCT01300234; GSK Clinical Study Register 114648.
在中国以外的地区，长期使用富马酸替诺福韦二吡呋酯（TDF）已证明能抑制病毒复制。本研究旨在评估 TDF 在中国慢性乙型肝炎病毒（HBV）感染患者中长达 240 周的疗效、耐药性和安全性。
在 48 周的双盲期（N=498）中，随机接受 TDF 300mg 或阿德福韦酯（ADV）10mg 每日一次治疗的患者（HBeAg 阳性或 HBeAg 阴性）有资格进入 TDF 开放标签期（TDF-TDF 和 ADV-TDF 组），再接受额外 192 周的治疗。
总体而言，512 名随机患者中有 457 名（89.3%）完成了 240 周的治疗。在第 240 周时，TDF-TDF 和 ADV-TDF 组的 HBeAg 阳性患者中分别有 84.5%和 87.9%、HBeAg 阴性患者中分别有 89.6%和 89.5%达到病毒学抑制。两组中大多数患者的丙氨酸氨基转移酶水平均恢复正常。与 ADV-TDF 组相比，TDF-TDF 组的 HBeAg 丢失（41.7%比 36.4%）和 HBeAg 血清学转换（32.0%比 28.3%）更为常见。TDF-TDF 组仅 1 例 HBeAg 阳性患者在第 240 周时 HBsAg 丢失。未观察到对 TDF 的耐药性。两组的不良反应发生率相似（TDF-TDF，56.4%比 ADV-TDF，51.6%）。1 例患者血清肌酐升高≥0.5mg/dL 基线以上，3 例患者出现确诊的 3/4 级磷异常（<2mg/dL）。
在慢性 HBV 感染的中国患者中，TDF 长期治疗可持续抑制病毒复制，240 周内未发生耐药。在该患者人群中，未发现 TDF 的新安全性问题。
临床试验注册ClinicalTrials.gov 标识符 NCT01300234；GSK 临床研究登记号 114648。
