以前在LAM / ADV治疗中失败的慢性乙型肝炎患者的基于替诺福

StephenW

VIRAL HEPATITIS
Five-year efficacy and safety of tenofovir-based salvage therapy for patients with chronic hepatitis B who previously failed LAM/ADV therapy
Authors

    First published: 22 December 2016Full publication history
    DOI: 10.1111/liv.13331  View/save citation
    Cited by (CrossRef): 0 articles Check for updates

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    Funding Information

    Funding information

    Gilead Sciences donated tenofovir for the study.
    Handling Editor: Jürgen Rockstroh

Abstract
Background

Multidrug-resistant HBV continues to be an important clinical problem. The TDF-109 study demonstrated that TDF±LAM is an effective salvage therapy through 96 weeks for LAM-resistant patients who previously failed ADV add-on or switch therapy. We evaluated the 5-year efficacy and safety outcomes in patients receiving long-term TDF±LAM in the TDF-109 study.
Methods

A total of 59 patients completed the first phase of the TDF-109 study and 54/59 were rolled over into a long-term prospective open-label study of TDF±LAM 300 mg daily.
Results

Results are reported at the end of year 5 of treatment. At year 5, 75% (45/59) had achieved viral suppression by intent-to-treat analysis. Per-protocol assessment revealed 83% (45/54) were HBV DNA undetectable. Nine patients remained HBV DNA detectable, however 8/9 had very low HBV DNA levels (<264IU/mL) and did not meet virological criteria for virological breakthrough (VBT). One patient experienced VBT, but this was in the setting of documented non-compliance. The response was independent of baseline LAM therapy or mutations conferring ADV resistance. Four patients discontinued TDF, one patient was lost to follow-up and one died from hepatocellular carcinoma.
Conclusions

Long-term TDF treatment appears to be safe and effective in patients with prior failure of LAM and a suboptimal response to ADV therapy. These findings confirm that TDF has a high genetic barrier to resistance is active against multidrug-resistant HBV, and should be the preferred oral anti-HBV agent in CHB patients who fail treatment with LAM and ADV.

StephenW

病毒性肝炎
以前在LAM / ADV治疗中失败的慢性乙型肝炎患者的基于替诺福韦治疗的五年疗效和安全性
作者

    首次发布：2016年12月22日全面的出版历史
    DOI：10.1111 / liv.13331查看/保存引用
    引用（CrossRef）：0篇文章检查更新

    文章的评分为10分
    资金信息

    资金信息

    吉利德科学捐赠替诺福韦用于研究。
    处理编辑：JürgenRockstroh

抽象
背景

多重耐药HBV仍然是一个重要的临床问题。 TDF-109研究表明，TDF±LAM对于先前失败的ADV附加或开关疗法的LAM抗性患者，经过96周的有效补救疗法。我们评估了在TDF-109研究中接受长期TDF±LAM的患者的5年疗效和安全性结果。
方法

共有59名患者完成了TDF-109研究的第一期，54/59被卷入长期前瞻性开放标签研究TDF±LAM 300 mg每日。
结果

结果在治疗的第5年末报告。在第5年，75％（45/59）通过意向治疗分析实现了病毒抑制。根据方案评估显示83％（45/54）HBV DNA检测不到。 9名患者仍然检测到HBV DNA，但8/9的HBV DNA水平（<264IU / mL）非常低，并且不符合病毒学突破（VBT）的病毒学标准。一名患者经历了VBT，但这是在记录不合规的情况下。该反应与基线LAM治疗或赋予ADV抗性的突变无关。 4例患者停止TDF，1例患者失访，1例死于肝细胞癌。
结论

长期TDF治疗似乎在LAM先前失败的患者和对ADV治疗的次优反应中是安全有效的。这些发现证实，TDF具有高耐药性的基因屏障，对多重耐药性HBV有活性，并且应该是用LAM和ADV治疗失败的CHB患者中优选的口服抗HBV药物。