AFP-L3和AFP mRNA联合检测在肝癌治疗疗效观察和预后中的作用

目的探讨甲胎蛋白(AFP)异质体(AFP-L3)和AFP mRNA联合检测在肝癌(HCC)治疗疗效观察和预后中的作用。方法联合检测AFP-L3、AFPmRNA在HCC患者中表达情况。结果 HCC患者的AFP mRNA(368.65±5.28)和AFP-L3(195.84±3.31)蛋白表达量均明显高于肝硬化组和肝良性病变组(t=23.32、30.15、30.21、25.46,均P<0.01)。另外,HCC患者的AFP阳性率(69.35%)和AFP-L3阳性率(79.03%)明显高于肝硬化组和肝良性病变组(χ2=5.78、10.98、14.52、26.23,均P<0.05)。62例HCC患者中,术后AFP转阴48例,其中AFP-L3仍为阳性18例,其1、2、3年生存率分别为72.22%(13/18)、44.44%(8/18)、22.22%(4/18);另外30例患者AFP和AFP-L3均为阴性,其1、2、3年生存率分别为80.00%(24/30)、53.33%(16/30)、50.00%(15/30);AFP和AFP-L3均转阴者的3年生存率明显高于AFP转阴而AFP-L3未阴者(χ2=3.98,P<0.05)。结论测定患者AFP mRNA和AFP-L3蛋白水平可以鉴定良、恶性肝病,对于HCC的早期诊断及预后判断有重要的临床意义。     

甲胎蛋白和甲胎蛋白异质体比率（AFP-L3%）对HBV相关早期肝细胞癌的诊断效能分析

目的 探讨甲胎蛋白（AFP）、AFP异质体L3(AFP-L3)在HBV相关早期肝细胞癌（HCC）中的诊断效能及最佳截断值。方法 纳入2019年1月—2022年7月在中山大学附属第三医院就诊的首次诊断且尚未治疗的HBV相关HCC患者（HCC组）共1 080例（其中中国肝癌分期Ⅰa～Ⅱa期肝癌620例）,346例慢性乙型肝炎患者（CHB组）和293例HBV相关肝硬化患者（LC组）为对照组,分析AFP和AFP-L3%筛查HBV相关早期HCC的诊断效能,包括灵敏度、特异度、受试者工作特征曲线下面积（AUC）等。偏态分布的计量资料两组间比较采用Mann-Whitney U检验,多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Bonferroni法。结果 HCC组AFP、AFP-L3%水平显著高于CHB组和LC组（H分别为542.479、418.974,P值均<0.001）。在早期HCC中,AFP和AFP-L3%最佳截断值分别为8.7 ng/mL和5%,AFP单用时AUC最高,为0.816,灵敏度和特异度分别为66.9%、85.1%;联合使用AFP-L3%与单用AFP的...     

甲胎蛋白异质体在原发性肝癌临床诊断中的应用

目的 通过临床大样本数据回顾性分析血清甲胎蛋白（AFP）和甲胎蛋白异质体（AFP-L3）诊断原发性肝癌（PLC）的价值。方法 2015年1月～2015年12月东方肝胆外科医院诊治的PLC患者7097例,同期诊治的肝硬化（LC）患者122例。采用化学发光法检测血清AFP水平,采用凝集素捕获微量离心柱法检测AFP-L3,将AFP-L3/AFP比值大于10%定义为AFP-L3阳性。结果 7097例PLC患者血清AFP水平为61.7（5.4,1226.0）μg/L,显著高于122例LC患者的3.6（2.5,10.95） μg/L（P<0.05）,AFP-L3阳性率为8.2（-,26.1）%,而在肝硬化患者未检出AFP-L3阳性（P<0.05）;以血清AFP≥20 μg/L或/和AFP-L3≥10%任一阳性为截断点,诊断PLC的准确度为63.1%,优于AFP（60.3%）和AFP-L3（47.9%）单独诊断的结果;AFP-L3阳性率随着AFP水平的升高而升高;血清AFP阴性的PLC和AFP阳性的LC患者AFP-L3阳性率分别为39.6%和7.7%,显著低于血清AFP阳性PLC患者的73.7%（P<0.05）;在2103例具有病理学诊断的PLC患者,1976例肝细胞癌（HCC）患者血清AFP水平为50.8（4.8,1015.0） μg/L,6例混合型肝癌患者血清AFP水平为74.9（4.55,39248.3） μg/L,AFP-L3阳性率分别为5.3（-,24.6）%和8.4（-,18.8）%,均显著高于121例肝内胆管细胞癌患者【2.8（2.2,5.15） μg/L,P<0.05】和【-（-,-）%,P<0.05】。结论 大样本的结果显示PLC患者血清AFP和AFP-L3存在较高的阳性率,其诊断效能较好。     

血清甲胎蛋白异质体对肝细胞癌的诊断意义

目的探讨甲胎蛋白异质体（AFP-L3）对肝细胞癌的诊断意义。方法采用电化学发光法和亲和吸附离心管法检测135例肝细胞癌和116例慢性肝炎和肝硬化患者血清AFP和AFP-L3。结果肝细胞癌患者血清AFP和AFP-L3阳性率明显高于良性肝病患者,差别有统计学意义（P〈0.001）;血清AFP-L3阳性与肿瘤大小无相关性（P〉0.05）。结论甲胎蛋白异质体在肝细胞癌的诊断中具有重要的价值。     

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。     

糖捕获法对肝病的鉴别诊断

目的:探讨采用糖捕获法检测甲胎蛋白异质体AFP-L3在鉴别良恶性肝病中的作用.方法:收集甲胎蛋白阳性肝病标本,应用装有耦联了小扁豆凝集素(LCA)的离心柱进行糖捕获分离甲胎蛋白异质体.采用化学发光法检测AFP和AFP-L3,并计算AFP-L3在AFP中的含量比例(AFP-L3%),分析AFP-L3%升高者与良恶性肝病的关系.结果:肝细胞癌患者血清中AFP-L3%显著高于于良性肝病患者(P<0.001),以AFP-L3%≥10%作为诊断指标,在已经确诊的肝癌患者中灵敏度为85%,肝炎和肝硬化特异度达到91.5%,急性肝炎阳性率54%,重型肝炎阳性率80%.AFP-L3%鉴别慢性肝病和肝癌,ROC曲线线下面积达到0.867.结论:糖捕获法检测甲胎蛋白异质体AFP-L3对良恶性肝病鉴别诊断具有重要临床意义,但不适合作为急性肝病和重型肝炎的肝癌早期鉴别检测.     

高尔基体蛋白73定量测定对肝细胞癌的诊断价值

目的：探讨血清高尔基体蛋白（GP73）检测用于肝细胞癌（HCC）辅助诊断的可行性。方法选择HCC患者145例（ HCC组）、肝炎与肝硬化患者128例（良性肝病组）、其他消化系统恶性肿瘤患者87例（肿瘤对照组）及健康体检者99例（健康对照组）,应用ELISA方法测定血清GP73,化学发光法测定甲胎蛋白（AFP）,计算二者单独检测与联合检测诊断HCC的敏感度和特异度。对HCC患者进行手术切除治疗,比较治疗前后血清GP73的变化情况。结果 HCC组血清GP73水平明显高于良性肝病组、肿瘤对照组和健康对照组（ P均＜0．01）。单项检测GP73的敏感度和特异度分别为71．0％、85．4％,AFP分别为46．2％、80．3％;联合检测GP73和AFP的敏感度和特异度分别为82．8％、78．3％。 HCC治疗后GP73水平较治疗前显著降低（P＜0．01）。结论 GP73对HCC有较好的诊断性能,可作为恶性肝病的独立指标与AFP互补应用于临床。     

转化生长因子-β1和AFP联检对肝癌诊断价值的研究

目的分析转化生长因子（TGF）-β1和甲胎蛋白（AFP）异常对肝癌（HCC）的诊断和鉴别价值。方法收集慢性肝病患者外周血，以酶联免疫吸附试验法（ELISA）测定慢性肝病、非肝肿瘤患者和正常对照者的血TGF—β1和AFP水平，分析两者在HCC早期诊断和鉴别方面的临床价值。结果HCC患者血TGF—β1呈异常表达水平，显著高于正常组、肝硬化、慢性肝炎和非肝肿瘤组。如以血TGF—β1浓度〉1．2μg／L、AFP浓度〉50μg／L为界，肝癌诊断的灵敏度分别为88．4％和63．7％，特异性分别为89．2％和75．7％。TGF—β1与血AFP浓度、肿块大小均无相关，两者联合检测可提高HCC诊断阳性率。结论血TGF—β1和AFP分析有助于肝癌的诊断和鉴别。     

肝细胞癌患者循环肿瘤细胞检测阳性率与射频消融治疗后短期疗效的相关性

目的探讨肝细胞癌(HCC)患者循环肿瘤细胞(CTC)的检出率与其他血清肿瘤标志物及射频消融治疗后短期疗效的相关性。方法选择37例HCC并进行射频消融治疗的患者,术前均进行CTC检测,并搜集患者临床特征、血清甲胎蛋白(AFP)、甲胎蛋白异质体(AFP-L3)的水平。术后1、3个月分别进行肝脏增强CT/MRI的检查,依据mRECIST标准评价患者的短期疗效,并应用Fisher精确检验法统计术前外周血CTC的检出率及其与AFP、AFP-L3肿瘤标志物水平、射频消融治疗后短期疗效的关系。结果术前CTC阳性患者为8例(21.6%)。其中巴塞罗那(BCLC)分期为0~A期20例,CTC检测阳性者7例(35%),BCLC分期为B~C期17例,CTC检测阳性者1例(5.9%),不同BCLC分期患者CTC阳性率有统计学差异(P=0.048)。经过射频消融治疗后,21例在1个月和3个月时进行疗效评价达完全缓解(CR),16例为部分缓解(PR)或在3个月内疾病进展。3个月内复查达到CR的21例有3例(14.3%)CTC检测阳性。疗后达PR或3个月内进展的16例中5例(31.3%)CTC阳性。两组无统计学差异(P=0.254)。8例CTC阳性的患者中有1例AFP400 ng/ml、5例AFP-L31;CTC阴性的29例患者中有8例表现为AFP400 ng/ml、4例表现为AFP-L31,两组AFP水平无统计学差异(P=0.649)、AFP-L3水平有明显差异(P=0.012)。结论初诊为中晚期HCC患者的CTC检测阳性率无显著提高,随AFP-L3水平升高CTC阳性率增高,但对于AFP而言该趋势不明显。     

甲胎蛋白异质体对诊断肝细胞癌的相关价值研究

目的评价甲胎蛋白异质体(AFP-L3)对于原发性肝癌(PHC)的诊断价值。方法收集本院2013年1月至2013年7月住院及门诊患者185例,包括PHC患者61例(PHC组)、肝硬化患者66例(肝硬化组)、慢性活动性肝炎患者58例(慢性肝炎组)。选择同期健康体检者60例为对照组。AFP-L3采用亲和吸附离心管分离血清,AFP和AFP-L3水平采用化学发光法检测,以AFP-L3≥10%为阳性诊断标准,计算AFP-L3的百分含量。结果 PHC组、肝硬化组、慢性肝炎组、对照组患者血清AFP-L3阳性率分别为78.02%、69.8%、78.26%、0%。PHC组患者AFP-L3水平与肝硬化组比较,差异无统计学意义(P=0.062)。PHC组患者AFP-L3水平与对照组比较,差异有统计学意义(P=0.031)。结论AFP-L3是国际公认的对PHC鉴别诊断的有用指标,但本研究显示其在良性肝病特别是肝硬化与PHC差别不明显,因此仍应与AFP及影像学联合检测更有利于PHC的诊断。     

定期随访对发现早期肝癌的重要性

目的评价随访对发现早期肝癌的重要性。方法 2004年1月至2009年6月于我院门诊检出早期肝癌患者共32人（其中直径≤3cm小肝癌患者20人）。分为随访检出组（筛查组）与非随访检出组（对照组）,比较早期肝癌检出率。早期肝癌组与中晚期肝癌组生存率比较。AFP-L3异质体、肝脏CT、MR对早期肝癌的诊断价值。结果 1.随访筛查组占所有早期肝癌患者75%,对照组占所有早期肝癌患者25%,二者差异有统计学意义（P〈0.01）;2.早期肝癌组较中晚期肝癌组其1年、2年、3年生存率高,二者差异有统计学意义（P〈0.01）;3.肝脏CT、肝脏MR与肝脏B超相比其对早期肝癌的检出率明显提高,二者之间差异有统计学意义（P〈0.01）。肝脏CT与肝脏MR相比其对早期肝癌的检出率无明显差异（P〉0.05）;4.AFP-L3对早期肝癌的阳性诊断率高;5.抗病毒治疗组与未抗病毒治疗组比较,其肝癌发病年龄晚,二者比较差异有统计学意义（P〈0.05）。结论定期随访工作至关重要,其对发现早期肝癌有极大意义,抗病毒治疗可延缓肝癌的发生时间。     

Lens culinaris agglutinin-reactive alpha-fetoprotein as a prognostic marker in patients with hepatocellular carcinoma undergoing transcatheter arterial chemoembolization

Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) is known to be a useful marker for the diagnosis of hepatocellular carcinoma (HCC). Recent studies have shown that positive AFP-L3 results after treatment predicts tumor recurrence and poor clinical outcome. This study was to evaluate the role of pretreatment AFP-L3 as a prognostic marker for response to transcatheter arterial chemoembolization (TACE) and survival in patients with HCC. Forty-six patients with HCC who underwent TACE were analyzed. Agglutinin-reactive AFP was measured by lectin-affinity electrophoresis coupled with antibody-affinity blotting. Agglutinin-reactive AFP results larger than 24.4% were considered to be positive. Agglutinin-reactive AFP fractions were positive in 32 patients. Agglutinin-reactive AFP-positive patients had poorer performance status, larger tumors, frequent portal vein thrombosis, and higher levels of serum AFP. The partial response rate to TACE was lower in AFP-L3-positive patients than in AFP-L3-negative ones (37.5% vs. 78.6%, p = 0.01). Tumor size and AFP-L3 were two independent predictive factors for response to TACE. The 2-year survival rate was lower in AFP-L3-positive patients than in AFP-L3-negative ones (21.2% vs. 78.6%, p = 0.01). Child-Pugh class, AFP-L3, the presence of portal vein thrombosis, and response to TACE were independent prognostic factors for survival. In conclusion, pretreatment status of AFP-L3 could be considered a useful marker for predicting clinical outcome in patients with HCC who underwent TACE.     

高尔基蛋白73、甲胎蛋白异质体3、甲胎蛋白和α-L-岩藻糖苷酶在肝脏疾病中的诊断价值

目的比较高尔基蛋白73(GP73)、甲胎蛋白异质体3(AFP-L3)、甲胎蛋白(AFP)和α-L-岩藻糖苷酶(AFU)在不同肝脏疾病患者中的意义及其单项或联合检测诊断肝癌的价值。方法对2013年1-12月收治的272例肝癌患者、203例肝硬化患者、248例慢性肝炎患者及210例健康体检者血清中的GP73、AFP-L3、AFP和AFU水平进行检测。非正态分布的数据多组间比较采用Kruskal-Wallis H检验,组间两两比较采用Mann-Whitney U检验,率的比较用卡方检验。ROC曲线绘制分别以健康人组和非肝癌组(健康体检、慢性肝炎、肝硬化)为对照。联合指标先进行Logistic拟合后再做ROC曲线。结果 GP73水平肝硬化组[177.0(116.0,247.0)ng/ml]较肝癌组[141.0(83.3,218.8)ng/ml])和慢性肝炎组[151.0(83.0,235.3)ng/ml]高(U=22 116.5、21 052.0,P均0.05);AFP-L3和AFP在肝癌组中的水平[11.3(4.3,21.2)%,78.4(7.1,2455.8)ng/ml]明显高于肝硬化组[6.0(4.0,8.0)%,10.0(3.8,49.5)ng/ml]和慢性肝炎组[7.0(5.0,9.0)%,18.8(4.4,79.6)ng/ml](P均0.05)。以健康人血清样本为对照绘制的诊断肝癌的ROC曲线,GP73、AFP-L3、AFP和AFU的ROC曲线下面积(AUC)分别为0.827、0.817、0.901和0.680。由此可知在鉴别健康人和肝癌患者方面,前3者比AFU有较高的准确性。以非肝癌患者血清样本为对照绘制的诊断肝癌的ROC曲线,4个指标对应的AUC分别为0.573、0.734、0.753和0.552,可见AFP-L3和AFP对于诊断肝癌有一定的准确性,其敏感性和特异性达到最大时的cut off值依次为8.55%(56.6%,84.9%),49.88 ng/ml(57.7%,80.9%)。结论 GP73的上升与肝损伤及长期纤维化有关,其在诊断肝脏疾病中有较好的敏感性,AFP-L3和AFP在诊断肝癌方面特异性较好,AFP-L3和AFP两者联合应用可提高肝癌的诊断敏感性至62.1%。     

Clinical utility of simultaneous measurement of serum high-sensitivity des-gamma-carboxy prothrombin and Lens culinaris agglutinin A-reactive alpha-fetoprotein in patients with small hepatocellular carcinoma

OBJECTIVE: To evaluate the diagnostic efficacy of simultaneous measurements of high-sensitivity des-gamma-carboxy prothrombin (H-DCP) and Lens culinaris agglutinin A-reactive alpha-fetoprotein (AFP-L3) in small hepatocellular carcinoma (HCC). METHODS: Sixty-one patients with small HCCs < or = 2 cm in diameter and 134 controls (chronic hepatitis: 59 cases; cirrhosis: 75 cases) were examined. H-DCP was measured by electrochemiluminescence immunoassay (cut-off 40 mAU/ml (milli-arbitrary units/ml) and AFP-L3% (percentage of AFP-L3/total AFP) by lectin-affinity electrophoresis coupled with the antibody-affinity blotting method (cut-off 10%). Fifty-six patients were histologically diagnosed and the remaining five patients were diagnosed clinically. RESULTS: Of 61 patients, 27 (44.3%) were positive for H-DCP and 14 (23.0%) were positive for AFP-L3. There was no correlation between H-DCP and AFP-L3%. Nineteen patients (31.1%) had positive H-DCP alone. Six patients (9.8%) had positive AFP-L3 alone, and in eight patients (13.1%) both markers were positive. In combination assay, 33 of 61 patients (54.1%) were positive for either marker; specificity and accuracy were 97.8% and 84.1%, respectively. There was a tendency for the AFP-L3% to be elevated in patients with moderately or poorly differentiated HCC (P= 0.0564) and multiple HCC nodules (P= 0.0316), while the H-DCP showed no elevation related to the tumour type. CONCLUSION: The detection rate of small HCC was improved by combination assay with H-DCP and AFP-L3%. Our results indicate that the markers are complementary and useful for the diagnosis and evaluation of small HCC when measured simultaneously.     

Usefulness of measurement of lens culinaris agglutinin-reactive fraction of α-fetoprotein as a marker of prognosis and recurrence of small hepatocellular carcinoma

OBJECTIVE: Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3%) is a recently described marker of hepatocellular carcinoma (HCC), and its usefulness has been demonstrated in many studies. We evaluated the usefulness of serial measurement of AFP-L3% as a marker of prognosis and recurrence after treatment of small HCC. METHODS: AFP-L3% was measured before and after initial treatment in 60 patients with small HCC (maximum diameter < or = 2 cm). AFP-L3% was taken as the ratio of AFP-L3 to total AFP and multiplied by 100%, and levels > or = 10% were considered positive. Outcomes and recurrence were compared between patients AFP-L3%-negative after initial treatment (Group A, n = 43) and patients who were AFP-L3%-positive after initial treatment (Group B, n = 17). RESULTS: Before treatment, AFP-L3% was positive in 14 (23.3%) of the 60 patients. The cumulative survival rate of Group A was significantly longer (p = 0.0091) than that of Group B. The recurrence rate was significantly higher in Group B (p = 0.0104) than in Group A. When recurrence was limited to intrahepatic metastasis, the recurrence rate was significantly higher in Group B (p = 0.0064). However, the recurrence rate of multicentric occurrence did not differ significantly between Groups A and B. CONCLUSIONS: Measurement of AFP-L3% after treatment may be useful for understanding prognosis and recurrence of HCC.     

Relationship between Lens culinaris agglutinin-reactive alpha-fetoprotein and pathologic features of hepatocellular carcinoma.

AIM: We investigated pathological features of Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) in order to seek a pathological basis of poor prognosis of HCC patients with elevated AFP-L3. METHODS: A total of 111 patients with HCC < or =5 cm in diameter who underwent hepatic resection were studied. Serum AFP-L3 concentration was measured within a month prior to surgery by lectin-affinity electrophoresis coupled with antibody-affinity blotting, and expressed as AFP-L3 percentage of total AFP. AFP-L3 of 10% or higher was judged to be positive. Pathologic features of resected HCC specimens were evaluated and classified concerning growth pattern (expansive or infiltrative growth), capsule formation, capsule infiltration, septal formation, portal vein invasion, hepatic vein invasion, bile duct invasion, and intrahepatic metastasis. These macroscopic and microscopic findings were compared between AFP-L3-positive and negative HCC specimens. RESULTS: Thirty-three (29.7%) were positive for AFP-L3. The prevalence of HCC with infiltrative growth, with capsule infiltration, with septum formation, with portal vein invasion, and with hepatic vein invasion was significantly higher in AFP-L3-positive group (P=0.0121, 0.0290, 0.0442, 0.0314, and 0.0433, respectively). These pathologic features reportedly indicate the progression of the tumor. CONCLUSIONS: AFP-L3-positive HCC had several pathologic features of progressed state of HCC, which accounted for the AFP-L3 as an indicator of poor prognosis of HCC.     

血清高尔基蛋白73、甲胎蛋白异质体3、甲胎蛋白和α-L-岩藻糖苷酶水平诊断原发性肝癌的效能分析*

目的 探讨应用血清高尔基蛋白体73（GP73）、甲胎蛋白异质体3（AFP-L3）、AFP和α-L-岩藻糖苷酶（AFU）水平诊断原发性肝癌（PLC）患者的效能。方法 2015年1月~2017年3月我院诊治的PLC患者261例,乙型肝炎肝硬化患者201例,慢性乙型肝炎患者238例和体检健康人200例,采用酶联免疫吸附试验法检测血清GP73水平,采用亲和吸附离心管法检测血清AFP-L3,采用全自动化学发光仪检测血清AFP,采用商用试剂盒检测血清AFU水平。绘制血清GP73、AFP-L3、AFP和AFU诊断PLC的ROC曲线,确定截断点（cut-off-value）,计算ROC曲线下面积（AUC）,判断它们的诊断效能。结果 肝癌组血清GP73水平显著低于慢性肝炎组和肝硬化组,差异有统计学意义（P<0.05）,血清AFP-L3显著高于其他3组,差异有统计学意义（P<0.05）,血清AFU水平显著高于健康人和肝硬化组,但低于慢性肝炎组,差异有统计学意义（P<0.05）;以非肝癌人群为对照,血清GP73、AFP-L3、AFP和AFU诊断肝癌的ROC曲线下面积分别为0.564（95%CI：0.485~0.636）、0.724（95%CI：0.555~0.786）、0.745（95%CI：0.654~0.806）和0.571（95%CI：0.385~0.536）,血清AFP-L3联合AFP诊断肝癌的截断点分别为8.25%和49.25 ng/ml,其灵敏度（Se）为55.5%,特异度（Sp）为85.0%,正确性（Ac）为80.1%,显著高于血清AFP-L3诊断的55.5%、85.0%和76.4%或AFP诊断的57.1%、82.7%和75.2%（P<0.05）;在261例肝癌患者中,血清AFP<9.6 ng/ml者71例（27.2%),其中PG73>106.5 ng/ml者30例（42.3%）,提示GP73对AFP阴性肝癌有一定的诊断价值;在201例肝硬化患者中,血清AFP<9.6 ng/ml者98例（48.8%）,其中PG73>106.5 ng/ml者52例（53.1%）,提示血清GP73水平容易受到肝硬化的影响。结论 应用血清AFP联合AFP-L3检测能够提高诊断肝癌的效能,但它们的灵敏度都还不够高,影响因素较多。临床医生需结合病史、影像学检查和动态血清学检测才能做出更为科学的结论。     

Clinicopathologic features of patients with intrahepatic cholangiocarcinoma who are seropositive for alpha-fetoprotein-L3 and those with combined hepatocellular and cholangiocarcinoma

BACKGROUND: Some patients who are seropositive for lectin-reactive alpha-fetoprotein (AFP-L3) have intrahepatic cholangiocarcinoma (ICC). There have been no studies regarding the features of ICC patients seropositive for AFP-L3. Thus, the purpose of the present paper was to compare the features of ICC patients from the viewpoint of two different tumor markers, AFP-L3 and carbohydrate antigen (CA) 19-9. METHODS: The ICC patients who underwent hepatectomy (n = 51) were divided into three groups, and their clinicopathologic features were compared: (i) group A, seropositive for AFP-L3 >or= 15%; (ii) group B, seropositive for CA 19-9 >or= 37 U/mL; and (iii) group C, seronegative for both AFP-L3 and CA 19-9. The features of combined hepatocellular and cholangiocarcinoma (n = 11) were also studied. RESULTS: Group A had a higher positivity rate for hepatitis viruses than group B (60%vs 20%, P < 0.05). More patients in group A were misdiagnosed as having hepatocellular carcinoma (HCC) at surgery (70%vs 5.7%, P < 0.001) who also had chronic liver disease (80%vs 25.7%, P < 0.01) than in group B. Seven, 10 and 11 of the 11 patients with combined hepatocellular and cholangiocarcinoma were seropositive for AFP-L3, CA 19-9 and hepatitis viruses, respectively. Ten were diagnosed as having HCC at surgery and nine had chronic liver disease. CONCLUSIONS: Patients with ICC seropositive for AFP-L3 and those with combined hepatocellular and cholangiocarcinoma have features close to HCC. The present study has, for the first time, identified a subgroup of ICC patients, seropositive for AFP-L3, having features close to HCC that are very different from those of the classical ICC patients seropositive for CA 19-9.