Liu Yingxia, Zhang Ying, Yuan Jing, Zeng Wen, Zhang Guoliang, Yao Simin, Li Huijuan, Yang Min, Deng Yong, Zou Rongrong, Li Shaxi, Xiao Jia
State Key Discipline of Infectious Diseases, Department of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China.
Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, China.
Hepatol Res. 2015 Oct;45(10):E43-52. doi: 10.1111/hepr.12454. Epub 2015 Jan 6.
In this prospective study, we aimed to evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in Chinese chronic hepatitis B (CHB) patients after multiple nucleoside/nucleotide analog (NA) treatment failures.
A total of 115 Chinese CHB patients with suboptimal response to two or more NA treatments were included in this study. All patients were changed to TDF (300 mg/day, oral administration) antiviral treatment for at least 72 weeks. Hepatitis B virus (HBV) polymerase (P) gene mutation screening for each patient was performed. In addition, virological, biochemical responses and estimated glomerular filtration rate (eGFR) of each patient at weeks 12, 24, 48 and 72 of TDF treatment were evaluated.
Seventy-six out of 115 patients had drug-resistance mutations (R(+) ), including 27 with adefovir (ADV)-associated mutations (35.5%) and 49 with lamivudine (LMV)-associated mutations (64.5%). For all included patients, complete viral response (CVR) of HBV DNA (<100 IU/mL) was 57.4%, 69.6%, 74.8% and 86.1% at weeks 12, 24, 48 and 72 of TDF treatment, respectively. Alanine aminotransferase normalization and hepatitis B e-antigen seroclearance occurred in 77.3% and 23.2%, respectively, after 72-week TDF treatment. CVR at weeks 12, 24 and 48 was observed more commonly in patients with baseline HBV DNA of less than 10(6) IU/mL. There was no significant reduction of eGFR induced by the TDF treatment.
Seventy-two-week treatment with TDF in Chinese CHB patients with previously multiple NA treatment failures exhibited effective and safe outcomes, which were independent of baseline mutations conferring ADV or LMV resistance.
在这项前瞻性研究中，我们旨在评估富马酸替诺福韦二吡呋酯（TDF）对多次核苷/核苷酸类似物（NA）治疗失败的中国慢性乙型肝炎（CHB）患者的疗效和安全性。
本研究共纳入115例对两种或更多种NA治疗反应欠佳的中国CHB患者。所有患者均改用TDF（300毫克/天，口服）进行抗病毒治疗至少72周。对每位患者进行乙型肝炎病毒（HBV）聚合酶（P）基因突变筛查。此外，评估每位患者在TDF治疗第12、24、48和72周时的病毒学、生化反应以及估计肾小球滤过率（eGFR）。
115例患者中有76例发生耐药突变（R(+)），其中27例有与阿德福韦（ADV）相关的突变（35.5%），49例有与拉米夫定（LMV）相关的突变（64.5%）。对于所有纳入患者，TDF治疗第12、24、48和72周时，HBV DNA的完全病毒学应答（CVR，<100国际单位/毫升）分别为57.4%、69.6%、74.8%和86.1%。TDF治疗72周后，丙氨酸氨基转移酶正常化和乙肝e抗原血清学清除率分别为77.3%和23.2%。基线HBV DNA低于10⁶国际单位/毫升的患者在第12、24和48周时更常观察到CVR。TDF治疗未导致eGFR显著降低。
TDF对先前多次NA治疗失败的中国CHB患者进行72周治疗显示出有效且安全的结果，这与赋予ADV或LMV耐药性的基线突变无关。
