替比夫定在接受核苷酸类似物治疗的慢性乙型肝炎患者中的

StephenW

In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue

    Authors
    Authors and affiliations

    Lung-Yi MakSze-Hang LiuDesmond Yat-Hin YapWai-Kay SetoDanny Ka-Ho WongJames FungTak-Mao ChanChing-Lung LaiMan-Fung YuenEmail author

    Lung-Yi Mak
        1
    Sze-Hang Liu
        1
    Desmond Yat-Hin Yap
        1
    Wai-Kay Seto
        12
    Danny Ka-Ho Wong
        12
    James Fung
        12
    Tak-Mao Chan
        1
    Ching-Lung Lai
        12
    Man-Fung Yuen
        12Email author

    1.Department of MedicineThe University of Hong Kong, Queen Mary HospitalPokfulamHong Kong
    2.State Key Laboratory for Liver ResearchThe University of Hong KongPokfulamHong Kong

Original Article
First Online: 06 July 2019

    114 Downloads

Abstract
Aim

Renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Early observational clinical data suggested that telbivudine (LdT) might have renoprotective effects.
Methods

In this prospective study, consecutive CHB patients on combined lamivudine (LAM) + ADV/TDF were switched to LdT + ADV/TDF at recruitment and were followed up for 24 months. Estimated glomerular filtration rate (eGFR) was calculated with the modification of diet in renal disease equation. The effects of LdT on cell viability and expression of kidney injury or apoptotic biomarkers were investigated in cultured renal tubular epithelial cell line HK-2.
Results

Thirty-one patients (median age 55 years, 90.3% male) were recruited (54.8% TDF: 45.2% ADV). Serum HBV DNA was undetectable at all time points. Median eGFR was 70.2 (IQR 62.6–77.9) and 81.5 (IQR 63.6–99.1) mL/min/1.73 m2 at baseline and 24 months, respectively (p < 0.001). Downstaging of chronic kidney disease was observed in eight (25.8%) patients and was more common in ADV-treated compared to TDF-treated patients (7/8 vs. 1/17, p = 0.011; OR 16, 95% CI 1.643–155.766, p = 0.017). In vitro data showed that adding LdT to ADV or TDF was associated with improved cell viability and lower expression of injury and apoptotic biomarkers compared with ADV or TDF alone. Treatment was prematurely discontinued in four(12.9%) patients due to myalgia.
Conclusions

Clinical and in vitro data suggest that LdT has renoprotective effects in patients on long-term ADV/TDF treatment. LdT may be considered as an adjuvant therapy in this special group of patients with renal impairment (NCT03778567).
Keywords
HBV Antiviral Nephrotoxicity Tenofovir Nucleoside analogues

StephenW

替比夫定在接受核苷酸类似物治疗的慢性乙型肝炎患者中的体外和体内肾脏保护作用

s
作者和隶属关系

麦龙行刘德恒叶德谦叶伟凯濑户黄丹豪

麦龙义
1个
刘思恒
1个
叶德谦
1个
怀基濑户
12
黄家豪
12
冯国荣
12
陈德茂
1个
赖庆龙
12
袁文峰
12电子邮件作者

1.香港大学薄扶林玛丽医院香港大学
2.香港大学肝脏研究国家重点实验室香港薄扶林

来源文章
首次在线：2019年7月6日

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抽象
目标

在慢性乙型肝炎（CHB）患者中，阿德福韦酯（ADV）和替诺福韦酯（FDF）的肾毒性是一个重大问题。早期的观察性临床数据表明，替比夫定（LdT）可能具有肾脏保护作用。
方法

在这项前瞻性研究中，连续接受拉米夫定（LAM）+ ADV / TDF联合治疗的CHB患者在招募时改用LdT + ADV / TDF，并随访了24个月。估计饮食后计算肾小球滤过率（eGFR）。在培养的肾小管上皮细胞株HK-2中研究了LdT对细胞活力和肾损伤或凋亡生物标志物表达的影响。
结果

招募了31名患者（中位年龄55岁，男性90.3％）（54.8％TDF：45.2％ADV）。在所有时间点均未检测到血清HBV DNA。在基线和24个月时，eGFR中位数分别为70.2（IQR 62.6–77.9）和81.5（IQR 63.6–99.1）mL / min / 1.73 m2（p <0.001）。在八名（25.8％）的患者中观察到慢性肾脏疾病的降级，并且与TDF的患者相比，ADV的患者更常见（7/8 vs. 1/17，p = 0.011； OR 16，95％CI 1.643– 155.766，p ＝ 0.017）。体外数据显示，与单独使用ADV或TDF相比，向ADV或TDF中添加LdT与改善细胞活力以及降低损伤和凋亡生物标志物的表达有关。四名（12.9％）患者因肌痛而提前终止治疗。
结论

临床和体外数据表明，LdT对长期ADV / TDF治疗的患者具有肾脏保护作用。 LdT可以被视为这一特殊的肾功能不全患者的辅助治疗（NCT03778567）。
关键词
乙肝病毒抗病毒肾毒性替诺福韦核苷类似物