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。     

血清异常凝血酶原Ⅱ对HBV相关肝细胞癌的诊断价值

目的研究血清AFP、维生素K缺乏或拮抗剂Ⅱ诱导蛋白(PIVKA-Ⅱ)单独或联合使用对HBV相关肝细胞癌(HCC)的临床诊断价值。方法选取2016年2月-2017年6月于徐州医科大学附属医院感染科实验室进行血清学检测的HBV相关HCC患者200例(其中手术治疗的患者80例)、乙型肝炎肝硬化患者143例、重度慢性乙型肝炎患者65例、慢性乙型肝炎肝衰竭患者42例,比较4组患者的AFP、PIVKA-Ⅱ水平。符合正态分布的计量资料多组间比较采用方差分析;不符合正态分布的计量资料多组间比较采用Krsukal-Wallis H检验,进一步两两比较采用Mann-Whitney U检验。计数资料组间比较采用χ~2检验。采用二元logistic进行逐步回归分析得出2项指标联合预测因子的新变量,利用受试者工作特征曲线计算AFP、PIVKA-Ⅱ单独或联合诊断HBV相关HCC的曲线下面积(AUC),AUC的比较采用De Long检验。结果 HBV相关HCC患者的AFP、PIVKA-Ⅱ水平高于其他3组,差异均有统计学意义(Z值分别为-9.432、-6.369、-2.158、-13.202、-9.609、-7.584,P值均0.05)。重度慢性乙型肝炎组及慢性乙型肝炎肝衰竭组的PIVKA-Ⅱ水平明显高于乙型肝炎肝硬化组(Z值分别为-2.977、-2.308,P值均0.05)。HBV相关HCC患者在手术治疗后5~7 d内的AFP、PIVKA-Ⅱ水平显著低于术前(Z值分别为-96.892、-76.997,P值均0.05)。PIVKA-Ⅱ检测HBV相关HCC的敏感度、特异度分别为84.0%、86.4%,AFP检测的敏感度、特异度分别为81.5%、50.4%;AFP、PIVKA-Ⅱ及AFP联合PIVKA-Ⅱ检测HBV相关HCC的AUC分别为0.757、0.905、0.912,PIVKA-Ⅱ与AFP的AUC比较,差异有统计学意义(Z=6.048,P0.001);二者联合对HBV相关HCC的临床诊断价值最高,明显高于AFP单独诊断价值(Z=7.814,P0.001)。结论血清PIVKA-Ⅱ水平对HBV相关HCC的诊断价值优于AFP,二者联合检测能提高HCC的检出率,降低误诊率。     

GPC3、GP73在肝细胞癌临床诊断中的价值

目的评价磷酯酰肌醇蛋白聚糖3(GPC3)、高尔基体蛋白73(GP73)的高表达对肝细胞癌(HCC)诊断价值。方法对39例HCC、31例肝硬化患者,基线时收集外周血及肝组织,采用ELISA法检测血清GPC3、GP73的表达量,实时定量逆转录PCR法(qRT-PCR)检测外周血单个核细胞(PBMC)及肝组织中GPC3 mRNA和GP73 mRNA的相对表达量;ROC曲线分析诊断的灵敏度、特异度等指标。结果 HCC组GPC3、GP73测量值显著高于肝硬化组(P0.001);GPC3诊断HCC的截断值9.3μg/L,ROC曲线下面积(AUC)=0.956,灵敏度为89.74%,特异度为96.77%,阳性预测值为97.2%,阴性预测值为88.2%,阳性似然比(+LR)27.82,阴性似然比(-LR)0.11;GP73诊断HCC的截断值77.68 ng/mL,AUC=0.937,灵敏度为92.31%,特异度为83.87%,阳性预测值为87.8%,阴性预测值为89.7%,+LR:5.72,-LR:0.092。结论 GPC3、GP73在HCC患者中表达明显增高,且灵敏度显著优于常规AFP,GPC3、GP73的特异度与常规AFP相近,因此GPC3、GP73有望成为一种新的较好、可靠的HCC无创诊断指标。     

时间-强度曲线对肝脏占位性病变的诊断价值

目的探讨超声造影(CEUS)及时间-强度曲线(TIC)对甲胎蛋白(AFP)阴性肝细胞癌(HCC)、AFP阳性HCC和肝血管瘤的诊断价值。方法选取2012年10月至2013年10月临床确诊的24例AFP阴性HCC、48例AFP阳性HCC和76例肝血管瘤患者,对3组病灶分别进行常规超声、CEUS和TIC分析,采用χ2检验比较3组的CEUS表现,采用方差分析,比较3组的TIC指标。结果 AFP阴性HCC与血管瘤的动脉期和实质期有统计学差异(χ2=39.4,P=0.001;χ2=78.9,P=0.001),AFP阳性HCC与血管瘤的动脉期和实质期差异有统计学意义(χ2=50.6,P=0.001;χ2=89.7,P=0.001),AFP阴性HCC、AFP阳性HCC动脉期和实质期差异无统计学意义(χ2=0.036,P=0.85;χ2=0.22,P=0.643);AFP阴性HCC、AFP阳性HCC和肝血管瘤峰值时间(TP)分别是(27.52±4.11)、(28.28±4.09)和(50.42±5.32)s,峰值强度(peak)分别是(49.52±4.31)%、(50.20±4.37)%和(47.83±4.29)%,ROC曲线下面积(AUC)分别是(1527.20±80.37)%s、(1725.08±78.46)%s和(1613.44±76.37)%s,平均通过时间(MTT)分别是(78.71±3.26)、(79.21±3.32)和(79.86±3.10)s,3组间TP差异有统计学意义(F=568.63,P=0.001),3组间peak值、AUC和MTT差异均无统计学意义(F=0.245、0.645、0.860,P值均0.05)。其中AFP阴性HCC与血管瘤组间TP差异有统计学意义(P=0.001),AFP阳性HCC与血管瘤组间TP差异有统计学意义(P=0.001),AFP阴性HCC与AFP阳性HCC组间差异无统计学意义(P0.05)。结论 CEUS表现和TP可鉴别诊断AFP阴性HCC(或AFP阳性HCC)和肝血管瘤,两者联合可提高肝脏良恶性病灶诊断价值,同时提高AFP阴性HCC的检出率。     

肝细胞癌患者GGT和甲胎蛋白的表达水平及相关性分析

目的探讨GGT和甲胎蛋白(AFP)在肝细胞癌(HCC)患者组织中的表达水平及相关性,评价其在HCC临床诊断中的应用价值。方法选择2011年12月-2014年12月在榆林市星元医院就诊的HCC患者84例和肝硬化患者76例,分析不同组别AFP和GGT表达水平的差异和相关性,并依据敏感性、特异性、约登指数、受试者工作特征曲线(ROC)和曲线下面积(AUC)确定诊断界值点。两组间比较采用独立样本t检验或Mann-Whitney U检验。相关性比较采用Spearman秩相关分析。结果 HCC组患者AFP和GGT的表达水平均高于肝硬化组,差异有统计学意义(Z值分别为-8.993、-7.647,P值均0.05)。HCC组和肝硬化组患者AFP和GGT的表达水平均存在正相关关系(rs值分别为0.531、0.416,P值均0.05);所有受试者AFP水平和GGT的表达存在正相关关系(rs=0.701,P0.05)。AFP和GGT对HCC的诊断准确性一般。AFP取界值为100 ng/ml时,其约登指数最大为0.519;GGT取界值为150 U/L时,约登指数最大为0.494。AFP和GGT联合诊断能够增加灵敏度、降低特异度,但是没有明显改变AFP诊断HCC的约登指数。结论 GGT和AFP的表达水平存在明显的正相关关系,但是AFP和GGT联合检测并没有显著改善HCC诊断的准确性。     

高尔基体蛋白73和透明质酸对HBV相关慢性肝病进展的诊断价值

目的探讨高尔基体蛋白73(GP73)与透明质酸(HA)在HBV相关慢性肝病进展中的临床应用价值。方法收集2016年12月-2017年4月就诊于青岛大学附属医院的患者142例,其中伴有肝硬化的肝细胞癌(HCC)36例(HCC组),乙型肝炎肝硬化66例(肝硬化组),慢性乙型肝炎(CHB)40例(CHB组)。另选取同一时期健康体检者30例作为对照。ELISA法检测血清中GP73浓度,化学发光法检测HA浓度。正态分布的计量资料多组间比较单因素方差分析;非正态分布的计量资料多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Mann-Whitney U检验。曲线分析比较GP73和HA单独或联合应用的临床诊断价值。受试者工作特征曲线下面积(AUC)比较采用Z检验,性别比、敏感度及特异度比较采用χ~2检验。结果 CHB组、肝硬化组及HCC组患者血清GP73和HA水平均高于对照组(P值均0.05)。肝硬化组、HCC组患者GP73和HA水平均明显高于CHB组(U值分别为677、637、291、193,P值均0.05)。肝硬化组内比较,失代偿期患者GP73与HA水平均显著高于代偿期患者(U值分别为171、212,P值均0.05)。对于CHB患者,GP73与HA联合检测的AUC及敏感度均高于GP73单独检测(0.950 vs 0.790,Z=2.32,P0.05;91.70%vs 72.20%,χ~2=5.14,P0.05)。预测肝硬化时GP73的诊断敏感度高于HA(87.90%vs 69.70%,χ~2=6.05,P0.05);二者联合应用较HA单独应用特异度降低(62.30%vs 86.80%,χ~2=14.60,P0.05),敏感度提高(93.90%vs69.70%,χ~2=11.80,P0.05)。诊断失代偿期肝硬化时GP73、HA联合应用敏感度高于HA单独应用(83.80%vs 67.60%,χ~2=4.17,P0.05)。GP73、HA和AFP诊断HCC的AUC分别为0.549、0.525、0.807,GP73与HA对HCC的诊断价值不如AFP(Z值分别为3.49、3.80,P值均0.05)。结论 GP73和HA均可作为监测HBV相关慢性肝病进展的辅助指标,联合应用对诊断肝硬化及肝硬化代偿情况具有重要的临床应用价值。     

血清铁蛋白测定对肝细胞癌的临床意义

本文研究血清铁蛋白作为肝细胞癌(HCC)一项新诊断指标的临床意义,并与AFP比较。作者前已报导铁蛋白浓度在AFP不高的HCC患者往往增高。采用放射免疫测定药盒测定空腹血清铁蛋白,计肝炎24例,肝硬化150例,HCC 132例,肝转移癌37例,正常人35例,并用放免法测定AFP。同时测定血清铁与SGOT、SGPT。以上病例均根据症状、体征、化验、B超、CT与动脉造影等诊断,HCC并经手术或尸解证实。结果:1.血清铁蛋白值:正常男性:59±11 ng/ml,女性27±6ng/ml(均值土标准差)。肝炎患者的最高值为969±326 ng/ml,与SGOT、SGPT值平行;肝硬化为169±14ng/ml;HCC为423±37ng/ml;肝转     

血清异常凝血酶原复合物、甲胎蛋白、铁蛋白检测对HBV相关肝细胞癌的辅助诊断意义

目的探讨血清异常凝血酶原复合物(PIVKA-Ⅱ)、甲胎蛋白(AFP)、铁蛋白(FER)单项及联合检测在HBV相关肝细胞癌(HCC)辅助诊断中的意义。方法收集2016年6月-2017年2月于天津市第二人民医院住院的40例HBV相关HCC、41例乙型肝炎肝硬化、44例慢性乙型肝炎患者及36例健康体检者的血清,并检测PIVKA-Ⅱ、AFP、FER水平,分别分析三者单独及联合检测诊断HBV相关HCC的受试者工作曲线下面积(AUC)、敏感度和特异度。非正态分布的计量资料组间比较采用非参数KruskalWallis H检验,进一步两两比较采用Mann-Whitney U检验。采用二元logistic进行逐步回归分析产生三项指标联合预测概率的新变量pre。结果血清AFP及PIVKA-Ⅱ水平在乙型肝炎肝硬化、慢性乙型肝炎、HBV相关HCC及健康对照组间的差异均具有统计学意义(χ~2值分别为51.446、59.613,P值均0.001)。AFP水平在HBV相关HCC组显著高于乙型肝炎肝硬化组、慢性乙型肝炎组及健康对照组(Z值分别为-4.609、-6.026、-6.031,P值均0.001),乙型肝炎肝硬化AFP水平也明显高于对照组(Z=-2.30,P=0.021);PIVKA-Ⅱ水平在HBV相关HCC组显著高于乙型肝炎肝硬化组、慢性乙型肝炎组及健康对照组(Z值分别为-6.080、-6.595、-5.608,P值均0.001),慢性乙型肝炎组PIVKA-Ⅱ水平也明显高于对照组(Z=-2.153,P=0.031);FER水平在HBV相关HCC患者组显著高于慢性乙型肝炎患者(Z=-2.177,P=0.029)。单项指标检测诊断HBV相关HCC时,AFP的敏感度最高(79.49%),但FER的特异度最高(94.28%);双项目检测方案中,AFP/PIVKA-Ⅱ方案的敏感度最高(89.74%),FER+AFP和FER+PIVKA-Ⅱ方案特异度较高(97.14%);三项目检测时,FER/AFP/PIVKA-Ⅱ方案的敏感度较高(92.31%),FER+AFP+PIVKA-Ⅱ特异度较高(97.14%)。结论 PIVKA-Ⅱ、AFP、FER三项联合检测可提高单独检测的敏感度及特异度。血清PIVKA-Ⅱ和AFP对HCC诊断具有较高的临床应用价值,单项即可很好辅助诊断,二者联合未提高诊断率。     

血清KLF5异常对良、恶性肝病诊断与鉴别诊断的临床价值

目的定量检测血液中锌指蛋白转录因子家族成员Krüppel样因子5(Krüppel-like factor 5,KLF5)的表达水平,分析对良、恶性、慢性肝病患者的诊断与鉴别诊断价值。方法经医院伦理委员会同意收集住院慢性肝炎(CH)患者40例、肝硬化(LC)患者40例、肝细胞癌(HCC)患者80例血液,以及健康体检正常人(NC)40份血清作为正常对照,以酶联免疫吸附分析(ELISA)定量测定血清KLF5水平,分析其临床病理学特征,并与血清AFP浓度比较,以评价对良、恶性肝病的诊断与鉴别诊断价值;经生物数据库资料分析KLF5的组织来源,并分析不同HCC细胞株中KLF5表达状态。结果在NC、CH、LC和HCC组患者血清中均可检出KLF5和AFP表达,显示血清KLF5和AFP浓度,在HCC组均显著高于LC组、CH组和NC组(P0.001);如以血清KLF5800 ng/ml和AFP25 ng/ml为上界,其阳性率在HCC组分别为90.0%和68.8%,两者联检达93.8%;LC组为12.5%和32.5%;CH组为0和25.0%;NC组均未见阳性;诊断HCC受试者工作曲线(ROC)下面积,KLF5为0.88,优于AFP的0.76(P0.001);KLF5和AFP诊断HCC灵敏度为90.0%和68.8%,特异度为85.1%和69.4%,准确度为88.4%和69.8%,阳性预测值为87.7%和54.8%,阴性预测值为88.1%和75.9%;生物信息库资料证明HCC组织中KLF5高表达,不同HCC细胞株中均见KLF5异常表达。结论 KLF5为新的标志物,外周血中异常水平分析有助于HCC诊断及良、恶性肝病的鉴别诊断。     

基于PIVKA-Ⅱ、AFP和AFP-L3不同组合模式的肝细胞癌筛查策略探讨

目的探讨血清PIVKA-Ⅱ、AFP和AFP异质体(AFP-L3)的优化组合对肝细胞癌(HCC)筛查诊断的敏感度和特异度。方法收集2017年1月-2018年7月东部战区总医院全军肝病中心118例HCC患者和76例肝炎肝硬化住院患者的血清,分别检测PIVKA-Ⅱ、AFP和AFP-L3水平。比较各指标及其不同组合对HCC筛查的敏感度和特异度。偏态分布的计量资料2组间比较采用Mann-Whitney U检验;计数资料2组间比较采用χ2检验。分析PIVKA-Ⅱ、AFP及AFP-L3筛查HCC的效能,计算敏感度及特异度,并绘制受试者工作特征曲线(ROC曲线)。结果 HCC组PIVKA-Ⅱ、AFP水平均显著高于肝炎肝硬化组(Z值分别为7. 80、3. 80,P值均0. 001)。HCC组中PIVKA-Ⅱ、AFP、AFP-L3阳性比例均高于肝炎肝硬化组(χ2值分别为153. 36、83. 97、168. 82,P值均0. 001)。PIVKA-Ⅱ和AFP阳性率在HCC组差异无统计学意义(68. 6%vs 67. 8%,χ2=0. 02,P 0. 05),但在肝炎肝硬化组的差异有统计学意义(14. 5%vs 51. 3%,χ2=23. 37,P 0. 001)。PIVKA-Ⅱ和AFP-L3阳性率在HCC组差异有统计学意义(68. 6%vs 35. 6%,χ2=25. 83,P 0. 001),但在肝炎肝硬化组差异无统计学意义(14. 5%vs 9. 2%,χ2=1. 01,P 0. 05)。AFP和AFP-L3阳性率在HCC组差异有统计学意义(67. 8%vs 35. 6%,χ2=24. 50,P 0. 001),在肝炎肝硬化组差异也有统计学意义(51. 3%vs 9. 2%,χ2=31. 92,P 0. 001)。PIVKA-Ⅱ筛查HCC的ROC曲线下面积为0. 832,显著高于AFP的0. 662 (P 0. 01)和AFP-L3的0. 656(P 0. 01)。以PIVKA-Ⅱ 40 m AU/ml、AFP 10 ng/ml和AFP-L3 10%作为各自提示HCC可能的阳性界值,在ROC曲线中,PIVKA-Ⅱ和AFP的敏感度均为67. 8%,高于AFP-L3的55%。PIVKA-Ⅱ的特异度为85. 5%,高于AFP的48. 7%和AFP-L3的60%。PIVKA-Ⅱ、AFP和AFP-L3均阳性时,对HCC的筛查敏感度仅为29. 7%,但特异度提高至98. 7%。PIVKA-Ⅱ+AFP联合筛查HCC的敏感度为55. 9%,特异度为90. 8%。PIVKA-Ⅱ+AFP-L3联合筛查HCC的敏感度为30. 5%,特异度为98. 7%; AFP+AFP-L3联合筛查HCC的敏感度为34. 7%,特异度为93. 4%。结论在除外抗凝剂和胆汁淤积等因素影响的前提下,血清PIVKA-Ⅱ单项升高对HCC的筛查价值显著优于AFP或AFP-L3单项升高。PIVKA-Ⅱ或AFP任一指标升高可显著提高对HCC的筛查敏感度,PIVKA-Ⅱ、AFP和AFP-L3三者或两两同时升高可显著提高对HCC的筛查特异度。     

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。     

血清生长分化因子15和甲胎蛋白联合检测对HBV相关肝细胞癌的诊断价值

目的探讨血清生长分化因子15(GDF15)和AFP联合检测对诊断HBV感染相关肝细胞癌(HCC)的临床价值。方法选取2019年3月1日-2019年9月1日在武汉大学人民医院诊治的患者和健康体检者共225例,其中HBV感染导致的HCC患者(HCC组)97例,慢性乙型肝炎患者(CHB组)41例,健康体检者(NC组)87例,分别测定三组人群的GDF15和AFP水平。计量资料采用单样本Kolmogorov-Smirnov法检验各组数据是否符合正态性,正态分布资料多组间比较采用方差分析,进一步两两比较采用LSD-t检验;非正态分布资料多组间比较采用Kruskal-Wallis H检验,两两比较采用Mann-Whitney U检验。计数资料采用χ2检验。采用二元logistic回归分析得到GDF15和AFP联合的回归模型,并绘制GDF15和AFP单独或联合检测的ROC曲线,计算曲线下面积及灵敏度、特异度和约登指数。结果HCC组、CHB组和NC组的GDF15和AFP水平差异均有统计学意义(χ2值分别为53.77、119.12,P值均<0.01);HCC组GDF15水平明显高于CHB组和NC组(P值均<0.01);HCC组和CHB组AFP水平均显著高于NC组,且HCC组AFP水平显著高于CHB组,差异均有统计学意义(P值均<0.01)。ROC曲线分析显示,GDF15、AFP及二者联合诊断HCC的曲线下面积、灵敏度和特异度分别为0.752、74.0%和68.3%,0.660、45.8%和85.4%,0.816、88.4%和68.5%。结论GDF15和AFP联合检测可以提高HBV相关HCC的诊断性能,具有较高的临床价值。     

Elevation of endoglin (CD105) concentrations in serum of patients with liver cirrhosis and carcinoma

OBJECTIVE: Liver cirrhosis is considered as a premalignant state, as about 80% of hepatocellular carcinoma (HCC) is associated with liver cirrhosis. Although alpha-fetoprotein (AFP) has a high negative predictive value, its sensitivity for detecting HCC is poor. The aim of this study was to evaluate circulating endoglin (CD105) in the serum of patients with liver cirrhosis and at high risk for HCC. METHODS: CD105 and AFP serum concentrations were measured in 70 healthy and 94 nonliver-diseased controls and 130 patients with chronic liver diseases and HCC, respectively. RESULTS: Fifty-seven liver cirrhotic patients, 45 patients with liver cirrhosis plus HCC, 19 liver fibrosis patients and nine patients with HCC only were studied. Serum CD105 is significantly elevated in liver cirrhotic patients compared with healthy (P<0.0001) and nonliver-diseased controls (P<0.0001). Patients with liver cirrhosis and HCC show the highest CD105 concentrations being significantly elevated in comparison to liver cirrhosis (P=0.0006) and HCC only (P=0.0134). A stronger positive correlation exists between CD105 and AFP in the patient group suffering from liver cirrhosis and HCC (r=0.479, P=0.0015) than the obtained correlation between both markers in the group of patients diagnosed with liver cirrhosis alone (r=0.358, P=0.0073). The logistic regression model identified CD105 as an independent marker (P=0.0077, odds ratio 1.3). CONCLUSION: CD105 has the potential to be a novel complementary biomarker that has some important bearing on the risk assessment for development of HCC in cirrhotic patients.     

Assessment of KL-6 as a tumor marker in patients with hepatocellular carcinoma

AIM: To investigate the clinical significance of KL-6 as a tumor marker of HCC in two different ethnic groups with chronic liver disease consecutively encountered at outpatient clinics. METHODS: Serum KL-6 was measured by the sandwich enzyme immunoassay method using the KL-6 antibody (Ab) as both the capture and tracer Ab according to the manufacturer's instructions (Eisai, Tokyo, Japan). Assessment of alpha fetoprotein (AFP) and protein induced vitamin K deficiency or absence (PIVKA-Ⅱ) was performed in both groups using commercially available kits. RESULTS: A significantly higher mean serum KL-6 (556±467 U/L) was found in HCC in comparison with non-HCC groups either with (391±176 U/L; P<0.001) or without (361±161 U/L; P<0.001) liver cirrhosis (LC). Serum KL-6 level did not correlate with either AFP or PIVKA-Ⅱ serU/Levels. Using receiver operating curve analysis for KL-6 as a predictor for HCC showed that the area under the curve was 0.574 (95%CI = 0.50-0.64) and the KL-6 level that gave the best sensitivity (61%) was found to be 334 U/L but according to the manufacturer's instructions; a cut-off point of 500 U/L was used that showed the highest specificity (80%) in comparison with AFP and PIVKA-Ⅱ (78% vs 72% respectively). Combining the values of the three markers improved specificity of AFP for HCC diagnosis from 78% for AFP alone; 93% for AFP plus PIVKA-Ⅱ to 99% for both plus KL-6 value (P<0.001). Mean serum alkaline phosphatase level was significantly higher in KL-6 positive (564±475) in comparison with KL-6 negative (505±469) HCC patients (P = 0.021), but such a difference was not found among non-HCC corresponding groups. CONCLUSION: KL-6 is suggested as a tumor for HCC. Its positivity may reflect HCC-associated cholestasis and/ or local tumor invasion.     

Alpha-L-fucosidase as a serum marker of hepatocellular carcinoma in Thailand

To evaluate the role of serum alpha-L-fucosidase (AFU) in the diagnosis of hepatocellular carcinoma (HCC), we simultaneously studied both AFU activity and alpha-fetoprotein (AFP) level in 60 patients with HCC, 60 patients with cirrhosis and chronic hepatitis each, 30 patients with other liver tumors and 60 healthy subjects. Serum AFU activity in patients with HCC (1,418.62 +/- 575.76 nmol/ml/hr) was significantly higher than that found in cirrhosis (831.25 +/- 261.13 nmol/ml/hr), chronic hepatitis (717.71 +/- 205.86 nmol/ ml/hr) or other tumors (706.68 +/- 197.67 nmol/ml/hr) and in controls (504.18 +/- 121.88 nmol/ml/hr, p < 0.05). With 870 nmol/ml/hr (mean value of controls plus 3 standard deviations) considered as the cut-off point, AFU was more sensitive (81.7 vs 39.1%) but less specific (70.7 vs 99.3%) than AFP at a level of > 400 ng/ml as a tumor marker of HCC. With both markers combined, the sensitivity was improved to as much as 82.6%. AFU activity in HCC patients was correlated to tumor size (r = 0.3529, p = 0.006) but not associated with tumor staging classified by Okuda's criteria (p = 0.1). The AFU activity in the viral hepatitis group (hepatitis B or C) was also significantly higher than in the non-viral group (p = 0.0005). We conclude AFU to be a useful marker, in conjunction with AFP and ultrasonography, for detecting HCC, particularly in patients with underlying viral hepatitis and cirrhosis.     

Hepatocellular carcinoma progression in hepatitis B virus-related cirrhosis patients receiving nucleoside (acid) analogs therapy: A retrospective cross-sectional study

BACKGROUNDAntiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma (HCC). Furthermore, there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog (NA) therapy.AIMThe study aim was to clarify risk factors and the diagnostic value of alpha-fetoprotein (AFP) for HCC progression in NA-treated hepatitis B virus (HBV)-related cirrhosis patients.METHODSIn this retrospective cross-sectional study, we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital. The patients were divided into two groups, 145 who did not progress to HCC (No-HCC group), and 121 who progressed to HCC during NA treatment (HCC group). The logistic regression analysis was used to analyze the risk factors of HCC progression. The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic (ROC) curve analysis.RESULTSUnivariate analysis showed that age ≥ 60 years (P = 0.001), hepatitis B and alcoholic etiology (P = 0.007), smoking history (P < 0.001), family history of HBV-related HCC (P = 0.002), lamivudine resistance (P = 0.011), HBV DNA negative (P = 0.023), aspartate aminotransferase > 80 U/L (P = 0.002), gamma-glutamyl transpeptidase > 120 U/L (P = 0.001), alkaline phosphatase > 250 U/L (P = 0.001), fasting blood glucose (FBG) ≥ 6.16 (mmol/L) (P = 0.001) and Child-Pugh class C (P = 0.005) were correlated with HCC progression. In multivariate analysis, age ≥ 60 years [hazard ratio (HR) = 3.089, 95% confidence interval (CI): 1.437-6.631, P = 0.004], smoking history (HR = 4.001, 95%CI: 1.836-8.716, P < 0.01), family history of HBV-related HCC (HR = 6.763, 95%CI: 1.253-36.499, P < 0.05), lamivudine resistance (HR = 2.949, 95%CI: 1.207-7.208, P = 0.018), HBV DNA negative (HR = 0.026, 95%CI: 0.007-0.139, P < 0.01), FBG ≥ 6.16 mmol/L (HR = 7.219, 95%CI: 3.716-14.024, P < 0.01) were independent risk factors of HCC progression. ROC of AFP for diagnosis of HCC was 0.746 (95%CI: 0.674-0.818). A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609, and specificity of 0.818 for diagnosing HCC.CONCLUSIONAge ≥ 60 years, smoking history, family history of HCC, lamivudine resistance, HBV DNA negative, FBG ≥ 6.16 mmol/L were risk factors of HCC progression. Serum AFP had limited diagnostic value for HCC.     

循环血单核细胞GPC-3mRNA和甲胎蛋白对肝癌诊断与转移监测的潜在价值

目的分析肝癌患者外周血单核细胞中磷脂酰肌醇蛋白多糖(GPC)-3 mRNA表达及甲胎蛋白(AFP)对肝癌诊断与转移监测的价值。方法收集住院肝病患者外周血,分离单核细胞,制备总RNA,经逆转录合成GPC-3cDNA,以荧光定量PCR扩增并分析其对肝癌诊断与转移监测的价值。结果外周血单核细胞中GPC-3 mRNA阳性仅见肝癌患者,55例肝癌患者中39例阳性(70.9%);肝硬化、肝炎、转移性肝癌、非肝肿瘤患者及正常对照组中未检出阳性(χ2=26.773,P<0.001)。外周血单核细胞GPC-3 mRNA阳性表达与HBsAg阳性(χ2=14.601,P<0.001)、肝癌的TNM分期(χ2=15.252,P<0.001)、门静脉癌栓(χ2=45.658,P<0.001)及伴肝外转移显著相关(χ2=22.273,P<0.001),与瘤体直径、数目、AFP浓度及分化程度间无明显相关;与血AFP可互补诊断,提高肝癌诊断阳性率(90.9%)。结论循环血单核细胞GPC-3 mRNA分析,有助于肝癌诊断和肝外转移监测,对AFP阴性肝癌具互补诊断价值。     

Serum alpha-fetoprotein levels and liver histology in patients with chronic hepatitis C

Objective: The clinical and morphological significance of a raised alpha-fetoprotein (AFP) level in patients with chronic hepatitis C is undefined. We sought to determine the relation between serum AFP level and liver histology in this population.
Methods: We reviewed the clinical and histological records of 200 consecutively evaluated patients with chronic hepatitis C whose serum AFP levels were recorded. Two groups were studied: group I = 125/200 (62%) patients with normal AFP, < 10 ng/ml; and group II = 75/200 (38%) patients with raised AFP, > 10 ng/ml. The groups were compared according to age, gender, duration of disease, histology, and history of alcohol abuse.
Results: There was no significant difference in serum AFP based on age, gender, alcohol consumption, or disease duration. Significant histological differences were observed: cirrhosis was present in 57 (45%) patients in group I versus 51 (68%) in group II (   p < 0.001  ). Hepatocellular carcinoma was more frequent in group II (14/75 [19%]) than in group I (1/125 [1%]) (   p < 0.001  ). Ten of 77 (13%) noncirrhotic patients and 51/108 (47%) cirrhotic patients had a raised AFP (   p < 0.002  ; relative risk, 3.262; confidence interval [C.I.], 1.912–5.564). A derived AFP level of 17.8 ng/ml maximized specificity for predicting histological outcome: one of 76 (1.3%), 29/108 (26.8%), and 14/15 (93.3%) patients were noncirrhotic, cirrhotic, or had HCC, respectively. This derived AFP value is 35% sensitive and 98.6% specific for cirrhosis, with a positive predictive value of 97.7%.
Conclusions: A serum AFP level >17.8 ng/ml strongly suggests the diagnosis of cirrhosis in a population of patients with chronic hepatitis C.     

Diagnostic accuracy of des‐gamma‐carboxy prothrombin for hepatocellular carcinoma in a French cohort using the Lumipulse® G600 analyzer

The increasing incidence of hepatocellular carcinoma (HCC) in Western countries requests reliable tumour markers for preclinical diagnosis. We evaluated the diagnostic accuracy of des‐gamma‐carboxy prothrombin (DCP), in comparison with alpha‐fetoprotein (AFP) in a French cohort using a new analyser. One hundred and sixty‐two patients with virus‐related cirrhosis (46 HCC patients and 116 controls) were recruited in this retrospective proof‐of‐concept study. DCP was measured on new Lumipulse^® G600 analyzer and AFP on usual Cobas e602 analyzer in serum samples that were collected at the time of HCC diagnosis for HCC patients or during follow‐up for controls. DCP and AFP levels were higher in HCC patients. The area under receiver operating characteristic curve was larger for DCP than for AFP (0.89 vs 0.77, P=.03). At the cut‐off value of 128 mAU/mL, sensitivity and specificity for DCP were 74% and 92%. At the cut‐off value of 20 μg/L, sensitivity and specificity for AFP were 63% and 82%. NRI_>0 for the association of “AFP+DCP” were 101%, P<.0001, and 23%, P=.03, compared to “AFP” or “DCP” alone, respectively. We conclude that DCP outperformed AFP for the detection of HCC.     

A Decrease in AFP Level Related to Administration of Interferon in Patients with Chronic Hepatitis C and a High Level of AFP

It is known that there is a very high incidence of hepatocellular carcinoma (HCC) among patients with type C chronic hepatitis and cirrhosis, and α -fetoprotein (AFP) has been widely used as a diagnostic marker for HCC. However, there are some patients showing continuous high AFP values but no evidence of HCC, and some studies have defined such patients as a high-risk group for HCC. In vitro study has shown that interferon (IFN) inhibits cell proliferation and enhances apoptosis as well as specific cytotoxic T lymphocytes against HCC, resulting in direct anticancer actions. In this study, we investigated the effect of IFN on AFP changes in chronic hepatitis C patients. Of 40 patients with chronic hepatitis C in whom diagnostic imaging confirmed the absence of HCC, 24 patients showed high pretreatment AFP values (high AFP group: AFP level > 10 ng/dl; mean ± SD, 46.3 ± 41.5 ng/dl) and 16 showed low pretreatment AFP values (low AFP group: pretreatment AFP level ≤ 10 ng/dl; mean ± SD, 5.3 ± 2.2 ng/dl). Pretreatment clinical parameters were statistically evaluated in relation to the AFP value. In the high AFP group, the platelet count, albumin level, and prothrombin (%) were significantly lower (P = 0.047, P = 0.0002, and P = 0.044, respectively), suggesting that AFP value increases with advancing liver disease. Subsequently 27 patients were administered IFN (IFN group), and the remaining 13 patients were administered Stronger Neo-minophagen C (SNMC), a glycyrrhizin preparation (SNMC group), as a control group receiving liver-protective therapy. Alanine aminotransferase was reduced in both the IFN and the SNMC group (mean, 132.56 to 60.07 mg/ml [P < 0001] and 147.85 to 56.23 mg/ml [P = 0.0240], respectively). AFP was significantly reduced in the IFN group (mean, 30.03 to 12.65 ng/ml; P = 0.0034), but there was no significant change in AFP in the SNMC group (mean, 29.70 to 39.17 ng/ml). AFP is useful for diagnosing HCC; however, some patients show a persistently high AFP level in the absence of HCC, and these patients have been described as a high-risk group for HCC. In this study, we found that IFN therapy but not SNMC universally reduced the AFP baseline. Since AFP is a significant predictor for HCC, therapeutic strategies for hepatitis C, e.g., long-term low-dose IFN treatment, may reduce hepatocarcinogenesis.