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抗线粒体抗体阴性原发性胆汁性胆管炎(PBC)的预后较差

2016-02-01 MedSci MedSci原创

胆管炎抗线粒体抗体
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冰岛大学医学院Juliusson近日完成的一项研究表明，与抗线粒体抗体(AMA)阳性的原发性胆汁性胆管炎(PBC)患者相比，AMA阴性者的预后显著较差。 研究者们对71例AMA阴性PBC患者的病历资料进行回顾性分析，按照诊断年度，与71例AMA阳性患者相匹配，记录患者的疾病表现、实验室检测结果和临床终点，对患者的长期转归进行评估。 结果，AMA阴性PBC患者的女性比例为96%，诊断

冰岛大学医学院Juliusson近日完成的一项研究表明，与抗线粒体抗体(AMA)阳性的原发性胆汁性胆管炎(PBC)患者相比，AMA阴性者的预后显著较差。

研究者们对71例AMA阴性PBC患者的病历资料进行回顾性分析，按照诊断年度，与71例AMA阳性患者相匹配，记录患者的疾病表现、实验室检测结果和临床终点，对患者的长期转归进行评估。

结果，AMA阴性PBC患者的女性比例为96%，诊断时的中数年龄为55岁，随访时间为7.5年，相比较，AMA阳性对照组的女性比例为86%，中数年龄为56岁，随访时间为8.3年。AMA阴性和阳性患者发病时的平均总胆红素水平分别为0.7 mg/dL和0.6 mg/dL，碱性磷酸酶水平分别为570 U/L和341 U/L(P>0.05)，两组患者的年龄、血清IgM水平、ANA状态和随访时间均无显著性差异。

值得注意的是，与AMA阳性患者相比，AMA阴性患者无肝脏相关并发症(包括肝移植和死亡)的生存率显著较低(P=0.0182)。

研究者指出，尚不清楚导致AMA阴性PBC患者预后较差的原因，可能是真正的预后较差，也可能反映了AMA阴性病例的检出延迟。


研究结果显示，89%患者存在大胆管PSC、4.3%存在小胆管PSC、6.4%合并自身免疫性肝炎（AIH）。69%患者存在IBD，其中有79.5%是溃疡性结肠炎（UC）。所有研究对象中，5年、10年、20年和总体非肝移植生存率分别为80.7%、72%、66.3%和65.6%，中位非肝移植生存期为14.5年。 

10.9％的患者诊断为肝胆管恶性肿瘤，结直肠癌为11.2%。女性比男性患者非肝移植生存率稍高（女性和男性分别为69%和63.9%）、肝胆管恶性肿瘤发病率低一些（女性和男性分别为7.9％比12.5％）。小胆管疾病患者和AIH患者具有显著较好的非肝移植生存率和较低的肝胆恶性肿瘤发病率。整体来看，IBD对生存率和恶性肿瘤发生率的影响轻微，统计学差异并不显著。


除了新近相关的9种基因区域，研究者还观察到3个既往与该疾病相关的基因组区域中的强信号。在这12个基因区域中，6个也与IBD相关，在最近一项有关IBD的研究中，另外6个区域与IBD无相关性。

“通过使用免疫基因分型芯片，我们能够区分这些自身免疫病之间的基因关系，并且开始不仅能看到它们的基因相似性，还能看到它们的基因差异性。”Jimmy Liu博士说。“由于PSC是一种罕见病症，因此样本采集比其他自身免疫病更加困难。我们希望获得的更多样本，从而能够将更多基因区域与该疾病联系起来，这样识别可作为治疗靶点的基础通路将变得更容易。”

3个与PSC相关的基因区域位于T细胞变异的基础单一生物学系统内。已知控制该通路的一个基因（HDAC7）是免疫耐受的一种关键因素，新数据强烈建议探索影响HDAC7功能的药物作为将来PSC靶点的可能性。

APT：万古霉素或能治疗原发性硬化性胆管炎

回顾1959年的少量病例已经提示，抗生素能够改善PSC患者的肝脏疾病。最近，研究者推测，“细菌延生分子”能够激活PSC患者的炎症和肝纤维化。为了进一步调查抗生素的潜力治疗作用，Tabibian博士和其团队随机分配35例PSC患者接受万古霉素治疗（125 mg或250 mg，4次/日）或甲硝唑治疗（250 mg或500 mg，3次/日），疗程为4周。“万古霉素，特别是低剂量万古霉素显示出有前景的治疗结果，”Tabibian博士说。“低剂量万古霉素治疗患者能够达到研究的主要治疗终点，伴有碱性磷酸酶（alkaline phosphatase，ALK）的降低。两种药物的较高剂量组似乎并不比低剂量组好。”

本文报道，事实上，12周时，所有万古霉素治疗患者均有较低的ALK。低剂量组ALK下降了43%（P=0.03），高剂量组ALK下降了40%（P=0.02）。两个低剂量组患者的ALK恢复正常。

低剂量甲硝唑组患者的胆红素降低20%（P=0.03），低剂量万古霉素组患者胆红素降低33%（P=0.06）。两种药物的低剂量组患者均显示Mayo PSC风险评分显著降低（万古霉素：0.55，P=0.02；甲硝唑：0.16，P=0.03）。高剂量甲硝唑组患者的瘙痒症状改善显著。本研究中，6例患者因为不良结果中断治疗，其中4例接受的是甲硝唑治疗。Tabibian博士补充说，万古霉素的耐受性好，特别是与其他PSC治疗药物相比较，例如强的松和其他免疫抑制剂。

原始出处：

Juliusson G, Imam M, Björnsson ES, Talwalkar JA, Lindor KD.Long-term outcomes in antimitochondrial antibody negative primary biliary cirrhosis. Scand J Gastroenterol. 2016 Jan 18:1-8.

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    2016-10-08 jiyangfei

    #原发性#

    0

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    2016-02-21 liuyong2980

    #PBC#

    0

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    2016-10-17 hb2008ye

    #胆汁性#

    0

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    2016-02-03 zhty5337

    #原发性胆汁性胆管炎#

    0

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    2016-02-03 108807375_62823132

    #胆汁#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1846482, encodeId=7a311846482a5, content=<a href='/topic/show?id=d3a33e0306d' target=_blank style='color:#2F92EE;'>#原发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37030, encryptionId=d3a33e0306d, topicName=原发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8e4c53, createdName=jiyangfei, createdTime=Sat Oct 08 21:24:00 CST 2016, time=2016-10-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1877844, encodeId=053118e7844c2, content=<a href='/topic/show?id=e6a71381456' target=_blank style='color:#2F92EE;'>#PBC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13814, encryptionId=e6a71381456, topicName=PBC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=de89102, createdName=liuyong2980, createdTime=Sun Feb 21 23:24:00 CST 2016, time=2016-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809362, encodeId=01b11809362a1, content=<a href='/topic/show?id=5eba834e876' target=_blank style='color:#2F92EE;'>#胆汁性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83478, encryptionId=5eba834e876, topicName=胆汁性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Mon Oct 17 14:24:00 CST 2016, time=2016-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1379007, encodeId=345c13e90078b, content=<a href='/topic/show?id=8f633e1073d' target=_blank style='color:#2F92EE;'>#原发性胆汁性胆管炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37107, encryptionId=8f633e1073d, topicName=原发性胆汁性胆管炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec53439, createdName=zhty5337, createdTime=Wed Feb 03 00:24:00 CST 2016, time=2016-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1579151, encodeId=6b6915e9151a1, content=<a href='/topic/show?id=372b834e673' target=_blank style='color:#2F92EE;'>#胆汁#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83476, encryptionId=372b834e673, topicName=胆汁)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2a0616505872, createdName=108807375_62823132, createdTime=Wed Feb 03 00:24:00 CST 2016, time=2016-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1628261, encodeId=c57f162826155, content=<a href='/topic/show?id=9a4e83503e4' target=_blank style='color:#2F92EE;'>#胆管#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83503, encryptionId=9a4e83503e4, topicName=胆管)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Wed Feb 03 00:24:00 CST 2016, time=2016-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=62926, encodeId=4c8a62926f4, content=对临床有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e4e21675717, createdName=卡莲, createdTime=Tue Feb 02 20:43:00 CST 2016, time=2016-02-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=62683, encodeId=8b5762683bb, content=收藏, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=240a1683959, createdName=李继凯, createdTime=Tue Feb 02 00:59:00 CST 2016, time=2016-02-02, status=1, ipAttribution=)]
    2016-02-03 一叶知秋

    #胆管#

    0

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    2016-02-02 卡莲

    对临床有用

    0

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    2016-02-02 李继凯

    收藏

    0

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