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CGH：肝癌标志物进展——α-AFP

2013-03-18 Clin Gastroenterol Hepatol EGMN

甲胎蛋白肝细胞癌
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　　《临床胃肠病学与肝病学》杂志4月刊发表的一项研究显示，血清α-甲胎蛋白(AFP)水平随时间改变与丙型肝炎患者发生肝细胞癌(HCC)之间存在关联(doi:10.1016/j.cgh.2012.11.029)。 　　主要研究者、密歇根大学的Elliot Lee博士指出：“假如能在今后的研究中得到证实，那么我们的发现将有助于开发针对丙型肝炎患者的个体化风险评估工具。” 　　在这项被称

　　《临床胃肠病学与肝病学》杂志4月刊发表的一项研究显示，血清α-甲胎蛋白(AFP)水平随时间改变与丙型肝炎患者发生肝细胞癌(HCC)之间存在关联(doi:10.1016/j.cgh.2012.11.029)。

　　主要研究者、密歇根大学的Elliot Lee博士指出：“假如能在今后的研究中得到证实，那么我们的发现将有助于开发针对丙型肝炎患者的个体化风险评估工具。”

　　在这项被称为“首个显示出AFP随时间改变的模式与发生HCC独立相关的大规模研究”中，Lee博士及其同事对参与HALT-C试验的患者进行了观察。在这项试验中，对此前抗病毒治疗无应答的丙型肝炎患者被随机分组，接受Peg干扰素或安慰剂维持治疗。根据试验方案，患者在头3.5年内每3个月接受1次筛查，此后在自愿的基础上每6个月筛查1次，筛查方法是检测血清AFP水平。

　　研究者将发生HCC的患者与随访时间相同、未发生HCC的对照者按1:3比例配对，“以排除随访时间较长者的HCC累计发生几率更大并且AFP检测值更多所造成的偏倚”。967例丙型肝炎患者中有82例在研究期间发生HCC，AFP检测的中位次数为18次(范围：5~22次)。随后，研究者分析了发生HCC与3种AFP变化模式之间的关联。

　　研究者首先评估了AFP上升率，定义为[患者在研究结束前或发生HCC前(以先到达者为准)最后1次AFP检测值+AFP基线值(入组时检测)]/90天。仅校正基线危险因素的简单logistic回归分析结果显示，AFP上升率与发生HCC的比值比(OR)为1.178有关(P＜0.001)，受试者工作特征(AUROC)曲线下面积为0.69。

　　然后，研究者计算了AFP标准差，定义为每例患者的所有AFP检测值的标准差。结果在同样的简单logistic回归分析中，AFP标准差每增加1个单位，发生HCC的OR值为1.026(P＜0.001)，AUROC曲线下面积为0.76。

　　第三步，Lee博士等人观察了最近的AFP检测值。结果显示，发生HCC的OR值为1.012(P＜0.001)，AUROC曲线下面积也是0.76。

　　最后，研究者合并分析了标准差和AFP上升率，并结合基线年龄、血小板计数和吸烟史，建立了一个“历史”模型，其AUROC为0.81，从而成为了更好的HCC预测因素。

　　研究者称：“AFP上升率与发生HCC之间的关系一目了然，但是应该如何解释标准差与HCC的关联呢？其生物学基础尚不明确，我们猜测AFP波动可能反映了肝内损伤和再生的循环，而参与再生的多种生长因子可刺激肝癌发生。”

　　研究者承认该研究存在一些局限性：“从临床实践的角度看，这些指标只有在患者接受至少2年随访的情况下才有用，因为需要较长时间才能显示出变化模式。此外，该研究仅纳入丙型肝炎患者，而我们并不清楚上述相关性是否也存在于其他慢性肝病中。”

与肝癌相关的拓展阅读：


Background & Aims
Current screening algorithms for hepatocellular carcinoma (HCC) view each testing interval independently, without considering prior test results. We investigated whether measurements of α-fetoprotein (AFP), over time, can be used to identify patients most likely to develop HCC.
Methods
We performed a nested case-control study using data from subjects in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis trial; 82 patients with HCC were matched 1:3 to individuals without HCC (controls), using bootstrap methods to ensure similar follow-up times between groups. We assessed the independent association between development of HCC and the following: (1) most recent level of AFP, (2) standard deviation in level of AFP, and (3) rate of increase in AFP using a multiple logistic regression that included patient-specific risk factors such as age, platelet count, and smoking status.
Results
In bivariable analysis, all 3 AFP metrics were associated with HCC development; the most strongly associated was the standard deviation of AFP (odds ratio, 1.03 per unit increase in standard deviation; P < .001). Incorporating the standard deviation of AFP and rate of AFP increase, along with patient-specific risk factors, improved the prognostic accuracy to an area under the receiver-operating characteristic curve of 0.81, compared with 0.76 when only the most recent AFP level was used.
Conclusions
Patterns of AFP test results can more accurately identify patients with hepatitis C and advanced fibrosis or cirrhosis most likely to develop HCC, compared with most recent AFP test results.

    

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    2014-02-10 mxj1971619

    #AFP#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1633246, encodeId=ece61633246f6, content=<a href='/topic/show?id=08a220e6ce' target=_blank style='color:#2F92EE;'>#AFP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2076, encryptionId=08a220e6ce, topicName=AFP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c9b922043063, createdName=mxj1971619, createdTime=Mon Feb 10 13:01:00 CST 2014, time=2014-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2058340, encodeId=65372058340e3, content=<a href='/topic/show?id=f6ba4546d1' target=_blank style='color:#2F92EE;'>#CGH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4546, encryptionId=f6ba4546d1, topicName=CGH)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8994206, createdName=chendoc242, createdTime=Thu May 23 05:01:00 CST 2013, time=2013-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1840759, encodeId=d8091840e5992, content=<a href='/topic/show?id=18bf61953d3' target=_blank style='color:#2F92EE;'>#标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61953, encryptionId=18bf61953d3, topicName=标志物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Thu Nov 28 11:01:00 CST 2013, time=2013-11-28, status=1, ipAttribution=)]
    2013-05-23 chendoc242

    #CGH#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1633246, encodeId=ece61633246f6, content=<a href='/topic/show?id=08a220e6ce' target=_blank style='color:#2F92EE;'>#AFP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2076, encryptionId=08a220e6ce, topicName=AFP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c9b922043063, createdName=mxj1971619, createdTime=Mon Feb 10 13:01:00 CST 2014, time=2014-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2058340, encodeId=65372058340e3, content=<a href='/topic/show?id=f6ba4546d1' target=_blank style='color:#2F92EE;'>#CGH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4546, encryptionId=f6ba4546d1, topicName=CGH)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8994206, createdName=chendoc242, createdTime=Thu May 23 05:01:00 CST 2013, time=2013-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1840759, encodeId=d8091840e5992, content=<a href='/topic/show?id=18bf61953d3' target=_blank style='color:#2F92EE;'>#标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61953, encryptionId=18bf61953d3, topicName=标志物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Thu Nov 28 11:01:00 CST 2013, time=2013-11-28, status=1, ipAttribution=)]
    2013-11-28 hukaixun

    #标志物#

    0