2019 EASL 信息速递 (Chinese) 王晖

StephenW

Hui Wang, MD, PhD
Ruijin Hospital Affiliated to Shanghai Jiaotong University       

2019 EASL 信息速递 (Chinese)
王晖
上海交通大学医学院附属瑞金医院

http://regist2.virology-educatio ... 9/8ACHA/13_Wang.pdf

lzqccxx

sw大神，麻烦解答一下，里面的数据，为什么恩替卡韦比TDF  患癌概率高了 10倍，这个数据看着，真不敢在吃恩替卡韦了！

StephenW

回复 lzqccxx 的帖子

谢谢你的问题. 医生和研究人员对这种差异也很感兴趣. 他们想了解是否真的存在显着差异，如果是，为什么会有差异. 因为差异是基于统计测量的，所以超出了我的理解力.

在香港的研究中我只能指出:
TDF研究人群更年轻，更多女性，更轻微的纤维化/肝硬化.

Editorial
January 2019 JAMA Oncol. 2019
"There remains a concern that the observed difference in HCC rates is due to residual confounding. This is a limitation of all observational studies, but Choi and colleagues5 used a robust analytic approach that included multiple subgroup analyses, the use of propensity scores and competing risks, as well as validation in a hospital-based cohort having data on disease severity and virologic responses. Remarkably, the association of ETV vs TDF and HCC risk was minimally changed by any of these adjustments. However, adherence to antiviral therapy and surveillance programs was not captured and may have influenced rates of HCC. Indeed, adherence of less than 90% to antiviral therapy in patients with CHB has been associated with a higher risk of HCC.10 Moreover, especially in countries where prior lamivudine exposure is prevalent, patients treated with ETV may be at increased risk of virologic breakthrough with time, and this, in turn, affects risk for HCC. Indeed, in the study by Choi and colleagues, there was a substantially higher rate of changing therapy in patients treated with ETV (12%) vs TDF (0.2%). Might reduced adherence and increasing rates of ETV resistance represent unmeasured confounders that contribute to the divergence in rates of HCC evident 2 years after initiation of therapy? Ideally, a randomized study design would help overcome these challenges and provide stronger evidence of the association between type of antiviral agent and HCC outcomes. As such a study seems unlikely, at least in the near term, we would advocate for additional observational cohorts with data on liver disease severity, virologic response, and adherence to surveillance to evaluate this important question."

社论
2019年1月JAMA Oncol。 2019
"仍然存在一种担忧，即观察到的HCC率差异是由于残留的混杂因素造成的。这是所有观察性研究的局限性，但Choi及其同事使用了一种强大的分析方法，包括多个亚组分析，倾向评分和竞争风险的使用，以及基于医院的队列中的验证，其中包含疾病严重程度和病毒学数据。响应。值得注意的是，ETV与TDF和HCC风险的关联在这些调整中几乎没有变化。然而，没有捕获抗病毒治疗和监测计划，可能会影响HCC的发病率。事实上，CHB患者对抗病毒治疗的依从性低于90％与HCC风险增加有关.10此外，特别是在拉米夫定暴露普遍存在的国家，接受ETV治疗的患者可能会增加病毒学突破的风险。随着时间的推移，这反过来会影响HCC的风险。事实上，在Choi及其同事的研究中，接受ETV治疗的患者（12％）与TDF（0.2％）相比，改变治疗的比率要高得多。可能降低依从性和增加ETV耐药率代表未测量的混杂因素，这些混杂因素导致治疗开始2年后HCC发生率明显不同？理想情况下，随机研究设计有助于克服这些挑战，并为抗病毒药物类型与HCC结局之间的关联提供更有力的证据。由于这样的研究似乎不太可能，至少在近期内，我们会提倡额外的观察性队列，其中包括肝病严重程度，病毒学应答和遵守监测的数据，以评估这一重要问题。"
       
。