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。     

血清寡糖链检测对HBV相关肝细胞癌的诊断价值

目的评价寡糖链检测(G-Test)试剂盒(荧光毛细管电泳法)辅助诊断HBV相关肝细胞癌(HCC)的临床价值。方法收集2017年8月-2018年6月就诊于北京佑安医院的患者血清样本310例,其中HBV相关HCC(HCC组)170例,乙型肝炎肝硬化(肝硬化组)50例,慢性乙型肝炎(肝炎组)85例,其他脏器恶性肿瘤(其他恶性肿瘤组)5例。检测血清寡糖链组分的相对浓度,计算并分析G-Test试剂盒在临床诊断中的灵敏度、特异度、总符合率和阳性预测值、阴性预测值,并与血清AFP进行方法学比较。非正态计量资料多组间比较采用Kruskal-Wallis H检验,进一步两两比较使用Dunn’s多重比较,计数资料两组间比较采用χ2检验。利用受试者工作特征曲线(ROC曲线)对诊断效能进行分析,利用logistic回归建立G-Test与AFP联合诊断模型,受试者工作特征曲线下面积(AUC)的比较采用Z检验。结果HCC组患者G值[6.46(5.73~7.07)]明显高于肝炎组[3.38(2.85~4.18)]及肝硬化组[3.99(3.13~5.21)]患者(H值分别为107.9、104.2,P值均<0.001)。HCC组患者AFP的水平明显高于肝炎组患者[0.77(0.45~1.77)log10 ng/ml vs 0.58(0.41~0.89)log10 ng/ml,H=33.65,P=0.025]。G-Test的灵敏度83.53%,特异度为74.29%,总体符合率为79.36%,阳性预测值79.78%,阴性预测值78.79%。G-Test与AFP单独诊断的AUC分别为0.846与0.611,G-Test的AUC明显高于AFP(Z=5.795,P<0.001),G-Test联合AFP诊断的AUC为0.870,明显优于G-Test(Z=2.523,P=0.012)与AFP(Z=6.943,P<0.001)单独诊断效能。HCC早期与中晚期组间G-Test检出率均高于AFP>400 ng/ml检出率(χ2值分别为26.441、38.379,P值均<0.001)。AFP分别以<20、<200、<400 ng/ml为阴性临界值,G-Test在AFP阴性的HCC患者中检出率分别为86.24%、85.93%、85.31%。结论G-Test的灵敏度和特异度较好,具有辅助诊断HCC的临床应用价值,联合AFP诊断效能更好。     

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。     

血清Talin-1在原发性肝细胞癌早期诊断中的作用

目的研究原发性肝细胞癌(hepatoce lloular carcinoma,HCC)患者血清中的踝蛋白1(Talin-1),并与传统的生物学标志物甲胎蛋白(alpha-fetoprotein,AFP)相比,探讨其在HCC早期诊断中的作用。方法采用酶联免疫吸附实验(enzyme linked immunosorbent assay,ELISA)分别检测120例血清样本中的Talin-1,包括HCC血清40例、肝硬化(liver cirrhosis,LC)血清40例、健康对照组血清40例。结果用ROC曲线创建一个Talin-1相对于AFP的诊断预测模型。HCC组Talin-1血清中的表达水平高于其他组(P0.05)。在HCC的诊断中,Talin-1诊断的准确性明显高于AFP相关的敏感性、特异性。结论 Talin-1在HCC的早期诊断中可能是一个潜在的标志物,并具有比传统的生物学标志物AFP更高的敏感性和特异性。     

肝硬化病人肝细胞增生与肝细胞癌风险

新近有报告认为肝细胞高度增生为肝细胞癌 (ＨＣＣ)发生的风险因素。本研究的目的旨在评估将肝细胞增生与临床和人口统计学特点综合考虑时 ,肝细胞增生是否为ＨＣＣ发生的独立风险因素。方法　回顾性研究 97例 1 988年至 1 994年肝活检证实为肝硬化而肝功能良好 (ＣｈｉｌｄＡ级和Ｂ级 )的病人的临床、组织学以及血液学特点。进行肝活检时均作了腹部超声检查 ,除明确系囊肿外 ,凡有任何肝内局部肿块者均被除外。所有这些病人均被列入ＨＣＣ早期诊断监督计划 ,并每隔 6个月对其进行腹部超声、血清ＡＦＰ和体格检查随访检查。ＨＣＣ诊断根据腹…     

超声造影鉴别肝硬化增生结节与肝细胞癌的价值探讨

目的：探讨超声造影在肝硬化增生结节和肝细胞癌（HCC）鉴别诊断中的应用价值。方法采用Sono Vue实时灰阶超声造影检查27个HCC和30个肝硬化增生结节,造影时记录并观察其动脉相、门脉相和实质相的动态造影变化及时间-强度曲线（TIC）的变化。结果 HCC病灶在CEUS的增强模式主要表现为快进快出（81.5%,22/27）和快进慢出（18.5%,5/27）,DN则呈多样化表现;HCC组超声造影后开始增强时间（11.48＆#177;2.87）s、增强达峰时间（23.27＆#177;7.75）s及峰值强度（PI）减半时间（84.85＆#177;21.93）s显著快于DN组（15.62＆#177;3.43）s、（37.89＆#177;14.99）s和（114.32＆#177;37.75）s,（P＆lt;0.05）,HCC组超声造影后PI（36.07＆#177;9.65）显著高于DN组（26.44＆#177;6.58）,（P＆lt;0.05）。结论 CEUS在HCC与DN的鉴别诊断中具有重要的临床应用价值。     

超声造影对肝细胞癌与肝转移癌的鉴别诊断价值分析

目的 研究超声造影(CEUS)检查肝转移癌(LM)与肝细胞癌(HCC)的表现特征和鉴别诊断价值。方法 2016年～2019年就诊于我院的肝脏占位患者117例,常规行CEUS检查,分析比较HCC与LM病灶在增强模式、开始增强时间、达峰时间和减退时间等方面的异同。结果 在77例HCC 患者中,有79个病灶,在40例LM患者中,有41个病灶;HCC病灶呈I型 增强为2.5%,II型为26.6%,III型为70.9%,而LM病灶分别为36.6%、9.8%和53.7%,差异显著(P＜0.05);HCC病灶增强达峰时间和减退时间分别为(29.16±7.87)s和(51.89±22.80)s,与LM病灶的【(25.98±5.30)s和(37.49±10.68)s,P＜0.05 】。结论 HCC与LM病灶在CEUS表现有一定的差异,对鉴别诊断具有很大的价值。     

一项用于早期诊断肝细胞癌的大规模多中心的血清代谢标志物研究

【据《Hepatology》2018年2月报道】题：一项用于早期诊断肝细胞癌的大规模多中心的血清代谢标志物研究（作者Luo P等）肝细胞癌是世界上第三大致死性癌症,由于缺乏有效的早期诊断的标志物,导致尚无满意的治疗方法。来自中国科学院大连化学物理研究所的Luo等报道了肝癌诊断的代谢标志物的鉴定与验证研究。从中国多个研究中心纳入1448例研究对象,包括健康对照人群、慢性乙型肝炎人群、肝硬化人群和肝癌人群。     

Assessment of the correlation between serum prolidase and alpha-fetoprotein levels in patients with hepatocellular carcinoma

AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 ± 10.1), 31 cirrhosis patients(mean age of59.3 ± 6.3) and 33 healthy volunteers(mean age of51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein(AFP) values with HCC clinicopathological features, such as tumor size,number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion(diameters; ≤ 3 cm, 3-5 cmand ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer(BCLC)criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alphafetoprotein levels were kept at-80 ℃ until use.Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay.RESULTS: In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number,presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls(P 0.001). Prolidase levels were significantly associated with tumor size and number(P 0.001, P = 0.002,respectively). Prolidase levels also differed in patients in terms of BCLC staging classification(P 0.001).Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis(P 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately(P = 0.032,P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation(r = 0.616; P 0.001) between prolidase and AFP values in terms of tumor size, number and BCLC staging classification,whereas the presence of macrovascular invasion did not show a positive association with serum prolidase and AFP levels.CONCLUSION: Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.     

肝硬化患者肝细胞癌的预防和治疗

肝硬化患者肝细胞癌的预防主要在于如何降低相关危险因素,尤其是对HBV、HCV相关性肝硬化的预防。HBV、HCV疫苗的应用是预防的关键,抗病毒药物预防有助于减少HBV、HCV的复制,降低HCC的发生率。HCC的根治治疗主要包括手术切除和肝移植,对于不能行根治的患者选用适当的非手术切除的多种介入疗法;其他治疗如辅以免疫治疗、分子靶向治疗也有助于改善肝细胞癌患者的预后。     

AFP阴性肝癌的肿瘤标志物诊断的研究进展

甲胎蛋白(alpha-fetoprotein,AFP)是肝细胞癌(hepatocellular carcinoma,HCC)的主要标志物,测定血清AFP水平是目前诊断HCC的主要手段.约1/3的HCC患者血清AFP水平正常,即所谓的AFP阴性肝癌,这部分患者的诊断是目前肝癌诊断中需解决的关键问题.多年来,人们一直在寻找能弥补AFP不足的肝癌标志物,以提高HCC的诊断水平.本文综述了有关AFP阴性肝癌的肿瘤标志物诊断研究进展,主要内容包括传统肝癌标志物对AFP阴性肝癌的诊断价值,新肝癌标志物对AFP阴性肝癌的诊断价值,以及对AFP阴性HCC具有潜在诊断价值的生物标志物.     

Surveillance and diagnosis of hepatocellular carcinoma in patients with cirrhosis

Early identification of hepatocellular carcinoma (HCC) is more frequent because of surveillance programs for HCC worldwide. The optimal strategy of surveillance in cirrhosis is a current topical issue. In terms of diagnosis, recent advances in non-invasive imaging technology, including various techniques of harmonic ultrasound, new ultrasound contrast agents, multi-slice helical computed tomography and rapid high quality magnetic resonance, have all improved the accuracy of diagnosis. Consequently the role of liver biopsy in diagnosis of HCC has declined. The imaging diagnosis relies on the hallmark of arterial hypervascularity with portal venous washout. However, with recent advances in genomics and proteomics a great number of potential serum and tissue markers have been identified and are being developed as new candidate markers for both diagnosis and prognosis of hepatocellular carcinoma, and may increase the need for liver biopsy.     

循环microRNA早期诊断肝细胞癌研究现状及方法学探讨

肝细胞癌（HCC）是发病率和死亡率很高的恶性肿瘤,对高危人群的筛查和监测十分重要。定期检查肝脏超声和血清AFP是目前主要的筛查手段,但灵敏度和准确性仍不尽如人意。microRNA与HCC的发生、转移、复发等病理过程密切相关,相关研究也方兴未艾。循环microRNA是HCC血清学标志物中的重要成员,在HCC诊断和筛查方面具有广阔的应用前景。选择合适的microRNA和确定高效的诊断方法是相关研究的重点,更多高质量的研究还在持续进行中。     

肝癌患者血清microRNA-21水平变化

目的：分析不同肝病患者血清microRNA-21（miR-21）水平,以探讨miR-21对肝细胞癌（HCC）的诊断价值。方法以实时定量逆转录PCR法检测正常人、慢性乙型肝炎（CHB）、肝硬化和HCC患者（各组均为25例）血清miR-21水平,分析miR-21水平与HCC临床病理学特征的关系。结果正常人、CHB和肝硬化患者血清miR-21相对水平分别为（1.1±1.7）、（2.3±2.6）和（2.8±2.5）,而HCC患者为（22.6±4.4）,显著高于前三组（P〈0.001）;HCC患者术后1w和1m血清miR-21相对水平分别为（18.4±3.5）和（3.1±2.7）,均较术前显著降低（P＜0.001）;HCC患者血清miR-21水平与肿瘤大小、癌栓以及HBV感染相关,与肿瘤分化程度、数目和血清AFP水平无相关性。结论 miR-21在HCC患者血清中显著升高,可能作为HCC早期诊断的潜在标志。     

肝硬化并肝细胞癌的端粒酶活性和氧化应激研究

为阐明端粒酶活性和氧化应激在肝细胞癌（HCC）合并肝硬化及肝硬化患者组织中的表达，相互关系及意义，采用TRAP－ELLISA方法测定了21例HCC合并肝硬化（下称HCC组）和23例肝硬化（下称肝硬化组）患者组织中的端粒酶活性，并用生化法测定其组织中的丙二醛（MDA），谷胱甘肽－S转移酶（GST）和总抗氧化能力（T－AOC）。结果显示，HCC组端粒酶阳性18例，阴性3例；肝硬化组阳性3例，阴性20例，两者差别有显著意义（P＜0．001）；MDA，GST和T－AOC在两组中的表达均有显著差异（P均＜0．001），端粒酶活性和MDA含量呈正相关（P＜0．05）。认为从肝硬化到肝癌的过程与机体抗氧化系统功能失调密切相关；端粒酶激活是HCC癌变的早期事件；氧化应激对端粒酶激活可能起重要作用。     

Chemoprevention of hepatocellular carcinoma in patients with hepatitis C virus related cirrhosis

Interferon(IFN) therapy has been reported to decrease the risk of hepatocellular carcinoma(HCC) and improve survival by preventing liver-related deaths in patients with chronic hepatitis C virus(HCV) infection, while the role of IFN therapy on the natural history of hepatitis C related cirrhosis is still under debate. The ideal goal of therapy is to prevent the progression into end-stage disease. The use of IFN in patients with HCV compensated cirrhosis reduces the negative clinical evolution independently of the type of laboratoristic and virological response. In our experience, IFN therapy in HCV compensated cirrhosis is barely useful in prevention of HCC, as cirrhosis itself represents a risk of cancer.Some authors noted that IFN treatment reduces the risk of HCC independently of the virological response. It would probably be interesting to evaluate the efficacy of weekly low-dose pegylated(PEG)-IFN therapy in patients with HCV cirrhosis and to assess potential benefits of long-term PEG-IFN plus Ribavirin treatment.     

Current state and clinical outcome in Turkish patients with hepatocellular carcinoma

AIM To investigate clinical, etiological, and prognostic features in patients with hepatocellular carcinoma.METHODS Patients with hepatocellular carcinoma who were followed-up from 2001 to 2011 were included in the study. The diagnosis was established by histopathological and/or radiological criteria. We retrospectively reviewed clinical and laboratory data, etiology of primary liver disease, imaging characteristics and treatments. ChildPugh and Barcelona Clinic Liver Cancer stage was determined at initial diagnosis. Kaplan-Meier survival analysis was done to find out treatment effect on survival. Risk factors for vascular invasion and overall survival were investigated by multivariate Cox regression analyses. RESULTS Five hundred and forty-five patients with hepatocellular carcinoma were included in the study. Viral hepatitis was prevalent and 68 patients either had normal liver or were non-cirrhotic. Overall median survival was 16(13-19) mo. Presence of extrahepatic metastasis was associated with larger tumor size(OR = 3.19, 95%CI: 1.14-10.6). Independent predictor variables of vascular invasion were AFP(OR = 2.95, 95%CI: 1.38-6.31), total tumor diameter(OR = 3.14, 95%CI: 1.01-9.77), and hepatitis B infection( OR = 5.37, 95 % CI : 1.23-23.39). Liver functional reserve, tumor size/extension, AFP level and primary treatment modality were independent predictors of overall survival. Transarterial chemoembolization(HR = 0.38, 95%CI: 0.28-0.51) and radioembolization(HR = 0.36, 95%CI: 0.18-0.74) provided a comparable survival benefit in the real life setting. Surgical treatments as resection and transplantation were found to be associated with the best survival compared with loco-regional treatments(log-rank, P 0.001).CONCLUSION Baseline liver function, oncologic features including AFP level and primary treatment modality determines overall survival in patients with hepatocellular carcinoma.