脱γ-羧基(异常)凝血酶原与肝细胞癌

脱γ-羧基(异常)凝血酶原(DCP)是一新发现的肝细胞癌(HCC)标志物。1984年Liebman等报告约90％HCC患者血浆中含有DCP。此     

增强磁共振成像联合血清甲胎蛋白和脱-γ-羧基凝血酶原诊断肝细胞癌临床价值探讨

目的探讨钆塞酸二钠(Gd-EOB-DTPA)增强磁共振成像(MRI)联合血清甲胎蛋白(AFP)和脱-γ-羧基凝血酶原(PIVKA-Ⅱ)诊断肝细胞癌(HCC)的临床价值。方法 2015年12月～2017年9月收治的82例肝病患者,经组织病理学诊断HCC组56例,非HCC组26例。罗氏cobas~? e 601型全自动电化学发光免疫分析系统检测血清AFP,采用LUMIPULSE G1200全自动免疫分析仪酶化学发光法检测血清PIVKA-Ⅱ。全部患者接受MRI检查。采用受试者工作特征曲线(ROC)下面积(AUC)判断各检查诊断的灵敏度、特异度和正确率。结果 HCC患者血清AFP和PIVKA-Ⅱ水平分别为34.5(4.5,594.9) ng/ml和63.5(25.0,2082.0) Mau/ml,显著高于非HCC组[分别为3.4(2.2,11.6) ng/ml和23.0(18.8,28.0) Mau/ml,P0.01];血清AFP、PIVKA-Ⅱ和Gd-EOB-DTPA增强MRI检查单独诊断HCC的ROC曲线下面积分别为0.763、0.815和0.907;在单项诊断HCC时,血清AFP和PIVKA-Ⅱ的最佳临床诊断截断点分别为14.4ng/ml和40.5 Mau/ml,其诊断HCC的灵敏度、特异度和准确率分别为64.3%、84.6%、67.4%和62.5%、100.0%、74.4%,Gd-EOB-DTPA增强MRI单独诊断HCC的灵敏度、特异度和准确率分别为92.9%、88.5%、91.5%,以Gd-EOB-DTPA增强MRI诊断的效能最高;采用联合试验Ⅰ诊断HCC,其灵敏度为98.2%,特异度为61.5%,准确率为86.6%,采用联合试验Ⅱ诊断HCC的灵敏度为50.0%,特异度为100.0%,准确率为50.0%。联合试验提高了诊断的特异度,但降低了灵敏度。结论应用血清AFP和PIVKA-Ⅱ检测联合Gd-EOB-DTPA增强MRI检查可提高诊断HCC的效能,综合应用三者联合诊断可以提高诊断HCC的正确性。     

降低AFP诊断阈值并联合检测DCP显著提高肝细胞癌的诊断率

目的评价甲胎蛋白(AFP)和脱-γ-羧基凝血酶原(DCP)联合检测对肝细胞癌(HCC)的诊断效能。方法选取临床诊断为HCC的患者75例和非HCC患者53例为研究对象,同时检测血清AFP和DCP浓度,分别绘制AFP、DCP和二者联合检测时的ROC曲线,计算最佳诊断阈值并评价其诊断效能。结果 AFP及DCP诊断HCC的ROC曲线下面积分别为0.789和0.882;当AFP诊断阈值降为22.6 ng/mL时,诊断效能最佳(灵敏度为66.7%、特异性为88.7%);DCP诊断HCC的最适阈值为39.0 mAU/mL,灵敏度为72.0%、特异性为94.3%;二者联合检测诊断HCC的灵敏度为77.3%、特异性为90.6%。结论 DCP对于HCC的鉴别诊断具有重要价值,降低AFP诊断阈值并联合DCP检测可显著提高对HCC的诊断率。     

γ-谷氨酰转肽酶和甲胎蛋白表达的相关性及其在肝细胞癌诊断中的价值

目的旨在分析γ-谷氨酰转肽酶(GGT)和甲胎蛋白(AFP)表达的相关性,同时从二者相关性的角度再次评价GGT在肝细胞癌(HCC)诊断中的准确性及价值。方法研究纳入2003年1月到2009年6月在卫生部中日友好医院住院治疗的HCC和肝硬化患者472例,分析GGT和AFP的相关性,诊断界值的确定主要依据受试者工作特征(ROC)曲线、曲线下面积(AUC)、敏感性和特异性,诊断价值以敏感性、特异性和正确指数来表示。统计学分析采用SPSS 17.0软件包。对于符合正态分布的计量资料,采用独立样本的t检验;对于偏态分布的计量资料,采用独立样本的非参数检验(Mann-Whitney U-test);对于计数资料,根据不同的条件分别采用Pearson卡方检验、连续校正卡方检验和Fisher精确检验。结果 472例患者中,包括HCC患者224例,肝硬化患者248例。GGT水平在2组患者中分别为113(58~254)U/L和38(22~72)U/L;AFP表达在2组中分别为429.5(15.7~1210.0)ng/ml和5.7(3.4~18.2)ng/ml;2组比较差异均存在统计学意义(Z=-11.037、-10.157,P均0.001)。GGT和AFP的相关性分析显示相关系数r=0.449,P0.001,GGT和AFP的AUC分别是0.784和0.788。GGT界值取60 U/L,AFP的界值取20 ng/ml,二者诊断的敏感性、特异性、正确指数分别为74.1%、70.2%、0.443和71.8%、77.6%、0.494。联合诊断的敏感性、特异性、正确指数分别为90.7%、58.7%和0.494。结论 GGT是HCC的生物标志物之一,其水平和AFP的表达存在明显的相关性,联合GGT可能不能明显增加AFP诊断HCC的准确性。     

γ-干扰素联合抗结核药物治疗肺结核临床疗效的Meta分析

目的:系统评价γ-干扰素(IFN-γ)联合抗结核药物治疗肺结核的临床疗效和安全性,为IFN-γ在肺结核临床治疗中的应用提供依据。方法:检索PubMed、Embase、中国生物医学文献数据库、中国知网、万方数据库,纳入自建库以来至2022年3月1日公开发表的IFN-γ联合抗结核药物治疗肺结核的临床随机对照试验(RCT)研究。根据Cochrane手册,应用Review Manager 5.4 软件对纳入文献进行质量评价。应用STATA 12.0 软件对IFN-γ联合抗结核药物治疗组(观察组)和单纯抗结核药物治疗组(对照组)肺结核患者治疗2~3个月及6~9个月后痰菌阴转率、病灶吸收率、空洞闭合率及两组不良反应发生率,以及治疗后外周血CD4⁺T细胞、CD8⁺T细胞百分比的差异进行评价。结果:共纳入18篇文献,共计1341例患者。Meta分析结果显示,与对照组比较,观察组患者治疗2~3个月和6~9个月后,痰菌阴转率RR(95%CI)值分别为1.40(1.26~1.56)和1.41(1.12~1.76);病灶吸收率RR(95%CI)值分别为1.43(1.09~1.88)和2.84(1.65~5.00);空洞闭合率RR(95%CI)值分别为2.07(1.47~2.92)和1.56(1.28~1.91),均显著高于对照组(P值均<0.05)。此外,与对照组比较,治疗后观察组外周血CD4⁺T细胞百分比升高更明显、CD8⁺T细胞百分比降低更明显(P值均<0.05), 加权均数差(WMD;95%CI)分别为5.18(2.53~7.84)和-3.16(-6.08~-0.23)。与对照组比较,观察组不良反应发生率RR(95%CI)值为1.06(0.70~1.60),其中,肝功能异常发生率、皮肤过敏反应发生率、胃肠道不良反应发生率RR(95%CI)值分别为1.02(0.95~1.11)、1.03(0.95~1.11)和1.01(0.93~1.11),差异均无统计学意义(P值均>0.05)。结论:IFN-γ联合抗结核药物治疗肺结核,可以促进患者病灶吸收、痰菌阴转率,且能改善肺结核患者的免疫指标。     

血清甲胎蛋白和高尔基体糖蛋白73联合检测对肝细胞癌的早期诊断价值

目的探讨血清甲胎蛋白(AFP)和高尔基体糖蛋白73(GP73)联合检测对肝细胞癌(HCC)的诊断价值,为早期诊断和鉴别诊断HCC提供依据。方法收集2012年6月-2013年5月住院患者标本共408例,其中HCC患者142例(HCC组),慢性肝炎患者156例(慢性肝炎组),肝硬化患者110例(肝硬化组)。分别采用电化学发光法和酶联免疫吸附试验(ELISA)双抗体夹心法测定3组患者的血清AFP和GP73的浓度,检测结果组间比较采用方差分析,率的比较采用χ2检验。并使用MedCalc统计学软件计算2项指标联合检测对HCC诊断的敏感度和特异度。结果 HCC组血清AFP和GP73的浓度显著高于肝硬化组和慢性肝炎组,差异具有统计学意义(P0.05);肝硬化组血清AFP和GP73的浓度显著高于慢性肝炎组,其差异亦有统计学意义(P0.05)。二者联合检测肝细胞癌的敏感度为95.8%,特异度为98.6%,较单项检测差异具有统计学意义(P0.05)。结论血清AFP和GP73联合检测对HCC具有较高的诊断价值和临床意义,可作为HCC早期的诊断和鉴别诊断指标,值得在临床上推广。     

血清高尔基体蛋白73诊断肝细胞癌价值探讨

目的评价血清高尔基体蛋白73（GP73）在肝细胞癌（HCC）诊断中的价值。方法选择400例HCC、100例肝硬化（LC）、100例慢性乙型肝炎（CHB）患者和200例健康对照者（HC）,分别采用ELISA和电化学发光法检测血清GP73和甲胎蛋白（AFP）水平;采用受试者工作特征曲线下面积（ AUROC）评估两者对HCC的诊断效能。结果 HCC、CHB和LC患者血清GP73水平分别为243.6±163.1ng/ml、85.6±35.3ng/ml和81.9±36.4ng/ml,均显著高于健康对照组（78.2±33.9ng/ml,P〈0.05）,但在CHB和LC组及HC三组间无统计学差异;GP73和AFP的最佳诊断临界值分别为150.7ng/ml和19.7ng/ml,GP73的AUROC为0.846,灵敏性为69.2%,特异度为90.5%,均显著优于AFP（AUROC为0.828,灵敏性为57.6%,特异度为88.1%,P〈0.05）;GP73与AFP两者联合检测可以进一步提高对HCC的诊断准确性（AUROC为0.887,灵敏性为73.5%,特异度为88.0%）;在AFP阴性与阳性的两组HCC患者中,GP73灵敏性和特异度无显著性差异。结论血清GP73对HCC的诊断效能高于AFP,两者联合检测可以进一步提高诊断效能。     

GALAD模型在诊断HBV相关肝细胞癌中的价值探讨

目的探讨GALAD模型在HBV相关肝细胞癌中的诊断价值。方法回顾性分析204例HBV感染住院患者,根据诊断分为HCC组及对照组,比较AFP、AFP-L3%、异常凝血酶原(DCP)、三项联合及GALAD模型诊断HCC的受试者工作曲线(ROC)下面积(AUC)、敏感性、特异性差异。结果HCC组中AFP、AFP-L3%、DCP及GALAD模型Z值水平均高于对照组,AFP、AFP-L3%、DCP单项、三者联合及GALAD模型诊断的AUC分别为0.760、0.742、0.865、0.887,0.937,GALAD模型AUC与三项标志物及其联合的AUC两两比较,差异均有统计学意义(P<0.05)。GALAD模型诊断的敏感性为83.82%,高于AFP、AFP-L3、DCP单项,与三项并联相当,特异性为86.03%。结论GALAD模型在HBV相关HCC诊断中显示了良好的效能,优于AFP、AFP-L3%、DCP及三项联合诊断,具有一定临床参考价值。     

外周血中性粒细胞与淋巴细胞比值联合甲胎蛋白对HBV相关肝细胞癌的诊断价值

目的 探讨外周血中性粒细胞与淋巴细胞比值(NLR)联合甲胎蛋白(AFP)对HBV相关肝细胞癌(HBV-HCC)的诊断价值.方法 回顾性纳入2019年1月至2020年6月南京医科大学附属江宁医院住院治疗的HBV-HCC患者64例(HBV-HCC组)和慢性乙型肝炎(CHB)患者132例(CHB组).收集患者年龄、性别、肝硬...     

磁共振成像评价肝动脉灌注化疗栓塞术治疗肝细胞癌疗效的价值

肝细胞癌(HCC)病情进展迅速,大多数患者就诊时已为较晚期或合并肝硬化,失去了外科手术治疗的机会,因此介入治疗成为肝癌目前非外科手术治疗的丰要手段.目前介入治疗比较常用的方法之一为肝动脉灌注化疗栓塞术(transcatheter anerial chemoembolization,TACE).由于TACE后仪有部分肿瘤组织完全坏死而不能一次性杀火肿瘤细胞,肿瘤易复发,故通常需要多次重复治疗.准确评价手术疗效并早期诊断肿瘤复发对进一步采取相应的治疗措施、提高患者生存率具有重要意义.现对目前磁共振成像(MRI)评价原发性肝癌TACE的疗效作一综述.     

Protein induced by vitamin K absence or antagonist-Ⅱ versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis

Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.     

应用血清PIVKA-II诊断肝细胞癌研究进展*

原发性肝癌（PLC）是我国最常见的恶性肿瘤之一,而早期诊断是对肝癌治疗能否获益的关键。维生素K缺乏或拮抗剂II诱导的蛋白（PIVKA-II）是近年来获得研究者广泛关注的一种新型肿瘤标志物,比甲胎蛋白诊断敏感性高。本文介绍了其在肝癌发病机制研究和临床应用方面的价值。     

基于2018年版肝脏影像报告数据系统对比分析CT和MRI诊断肝细胞癌的效能

目的 比较CT和MRI按照2018年版肝脏影像报告数据系统(LI-RADS)诊断肝细胞癌(HCC)的效能.方法 2017年9月～2020年7月四川省肿瘤医院诊治的有HCC高危因素的72例患者(HCC 53例、非HCC恶性肿瘤10例、良性病变9例),接受CT和MRI检查.根据2018年版LI-RADS定义的影像学征象和分...     

CT灌注成像在AFP阴性及增强CT表现不典型的HCC诊断中的价值

目的探讨CT灌注成像在AFP阴性及增强CT表现不典型的肝细胞癌（HCC）诊断及鉴别诊断中的应用价值。方法从2011年9月至2013年9月收治的HCC患者中随机选择14例进行研究,均予以64层螺旋CT灌注成像扫描。结果 HCC组病灶的平均通过时间（MTT）为（8.6±4.8）s,血管表面通透性（PS）为（28.8±19）mL·100 mL^-1·min^-1,较之非病灶区的（14.5±8.1）s和（59.1±26）mL·100 mL^-1·min^-1,均呈现出显著减少的情况;HCC组病灶的肝动脉灌注分数（HAF）为0.432±0.197,较之非病灶区的0.105±0.113,则呈现出显著增加的情况（均P〈0.05）。HCC组病灶的肝血容量（HBV）（30±20）mL/100 mL和肝血流量（HBF）（232±170）mL·100 mL^-1·min^-1较之非病灶区（25±16）mL/100 mL、（175±76）mL·100 mL^-1·min^-1差异均无统计学意义（均P〉0.05）。在HBF方面,肝血管瘤组病灶与HCC组病灶之间存在显著差异。肝局灶性结节增生与非结节区的各灌注参数大小基本一致,但肝局灶性结节增生的HAF小于非结节区。HCC组病灶灌注参数合患者血清AFP之间不存在明显的相关性,PS（r=-0.1022,P=0.7520）;HAF（r=-0.3138,P=0.2964）;MTT（r=0.0416,P=0.8926）;HBV（r=-0.2170,P=0.4765）;HBF（r=-0.2152,P=-0.4801）。结论 CT灌注成像在AFP阴性及增强CT表现不典型的HCC诊断及鉴别诊断中具有重要的应用价值。     

PIVKA-II:一种新型乙型肝炎相关肝癌诊断标记物研究进展

目的 病毒性肝炎,尤其是乙型肝炎病毒(HBV)感染是肝细胞癌(HCC)的主要致病因素。因缺乏早期症状,大部分HCC患者确诊时已为中晚期,因此预后不良。早诊断、早治疗是肝癌诊治的重要环节,现有的监测方法似乎不能显著提高肝癌的检出率。研究证实,维生素K缺失或拮抗剂-II诱导的蛋白质(PIVKA-II)有利于肝癌的早期诊断,本文对此进行了文献复习和综述。     

Pearls and pitfalls in magnetic resonance imaging of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the most common primary hepatic malignancy, which usually arises in cirrhotic liver. When the typical enhancement pattern, consisting of late arterial hyperenhancement followed by washout, is present in nodules larger than 1 cm, HCC can be confidently diagnosed without the need for tissue biopsy. Nevertheless, HCC can display an atypical enhancement pattern, either as iso or hypovascular lesion, or hypervascular lesion without washout. Not only the enhancement pattern of HCC could be atypical, but also a variety of histological types of HCC, such as steatotic, scirrhous, fibrolamellar, or combined hepatocellular-cholangiocellular carcinoma could raise diagnostic dilemmas. In addition, distinct morphological types of HCC or different growth pattern can occur. Awareness of these atypical and rare HCC presentations on magnetic resonance imaging is important for accurate differentiation from other focal liver lesions and timely diagnosis, which allows optimal treatment of patients.     

Performance of protein induced by vitamin K absence or antagonist-II assessed by chemiluminescence enzyme immunoassay for hepatocellular carcinoma detection: a meta-analysis

Objectives: In the setting of surveillance for hepatocellular carcinoma (HCC) detection, the use of serum biomarkers in addition to ultrasonography (US) is still a matter of debate. Hence, we performed a meta-analysis to evaluate the diagnostic accuracy of protein induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha-fetoprotein (AFP) alone or in combination for HCC detection in patients at risk of tumor development.

Materials and methods: We performed a systematic search in PubMed and Scopus database for original articles published in English from 2011 to 2017, investigating the accuracy of PIVKA-II alone or in combination with AFP (reported as area under the curve [AUC]) for HCC detection among patients at risk of tumor development. Furthermore, we focused on studies in which serum PIVKA-II was assessed by highly sensitive chemiluminescence immunoassay (CLEIA).

Results: A total of 11 studies (873 patients with HCC and 1244 patients with advanced liver disease/cirrhosis) were included in the meta-analysis. The weighted summary AUC (sAUC) of PIVKA-II and AFP for the discrimination between patients with HCC and those without was 0.791 (0.746–0.837) and 0.767 (0.732–0.803), respectively. The combination of PIVKA-II?+?AFP results in a sAUC of 0.859 (0.837–0.882). The performance for HCC detection of PIVKA-II?+?AFP was significantly superior to each biomarker used alone (ΔsAUC?=?0.068, p?=?.032 and ΔsAUC?=?0.092, p?Conclusion: In clinical practice, the use of PIVKA-II?+?AFP in addition to US examination may improve the effectiveness of surveillance among patients at risk for HCC development.