Glypican-3 and alphafetoprotein as diagnostic tests for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumor. It is usually asymptomatic in the early stages and tends to be intravascularly and intrabiliary invasive. Therefore, most patients present with incurable disease at the time of detection and early diagnosis of HCC is critical for a good prognosis.The imaging-based diagnosis of small tumors is relatively inaccurate, as cirrhotic and dysplastic nodules mimic HCC radiologically. The availability of a suitable serological marker to distinguish between HCC and benign liver lesions would, therefore, be very useful for early diagnosis. The only serological marker currently widely used for the diagnosis of HCC is alphafetoprotein (AFP). However, the sensitivity of this marker is limited (41-65%). Given the high heterogeneity of HCC, it is currently thought that an optimal serological test for HCC will be based on the simultaneous measurement of two or three highly specific serological markers.Several laboratories have recently reported that glypican-3 (GPC3), a membrane-bound proteoglycan, is expressed by a large proportion of HCCs, but is undetectable in normal hepatocytes and non-malignant liver disease. Furthermore, various studies demonstrated that GPC3 could be used as a serological test for the diagnosis of patients with HCC. Although the specificity of the test was very high in the context of a population with chronic liver disease, the sensitivity was limited (within the same range as AFP). Interestingly, in most cases, elevated GPC3 values did not correlate with elevated AFP values. As a consequence, the serological level of at least one of the two markers was elevated in a large majority of HCC patients. These results suggest that the sensitivity of the diagnostic test can be significantly improved without compromising specificity with the simultaneous measurement of both GPC3 and AFP.     

Comparing the diagnostic value of serum oligosaccharide chain (G-test) and alpha-fetoprotein for hepatitis B virus-related liver cancer

ObjectivesThe study compared the diagnostic efficiency of serum oligosaccharide chain (G-test) and alpha-fetoprotein (AFP) for hepatitis B-related hepatocellular carcinoma (HCC).MethodsSerum samples from 100 patients (divided into five groups of 20 each, namely the hepatitis, liver cirrhosis, liver cancer, health, and interference groups) who were admitted to the Second Affiliated Hospital of Nanchang University from October 2019 to January 2020 were collected, and the levels of G-test and AFP were determined. The sensitivity and specificity of the two indicators were compared, and the receiver operating characteristic curve of the subjects was drawn to evaluate the diagnostic values of G-test and AFP for HCC.ResultsThe diagnostic ability of G-test (area under the curve [AUC]: 0.88 ± 0.05) was better than that of AFP (AUC: 0.76 ± 0.05). When G-test and AFP were combined for detection, the AUC was larger than that of either indicator. The G-test was superior to AFP in the differential diagnosis of early HCC and cirrhosis. A combination of the two indicators (AUC: 0.769 ± 0.05) significantly improved the diagnostic rate for early HCC, indicating that G-test and AFP complemented each other.ConclusionG-test was better than AFP for screening HCC in patients with chronic hepatitis B and cirrhosis. The combination of the two further improved the diagnostic rate of hepatitis B-related liver cancer. The G-test improves the screening rate of early HCC in patients with cirrhosis. Therefore, these markers are of great clinical significance and can improve the sensitivity of HCC detection and reduce missed diagnosis rates.     

Recurrent hepatocellular carcinoma: usefulness of ultrasonography compared with computed tomography and AFP assay.

Follow-up studies using monitoring with alpha1-feto protein (AFP), ultrasonography (US), and computed tomography (CT) were carried out in 75 patients who had prior partial hepatectomy for hepatocellular carcinoma (HCC). Recurrence in the remaining liver was confirmed in 31 patients (41.3%) during the 4 month to 3 years 7 month period. Ultrasonography detected recurrence in 29 cases (sensitivity: 93.5%), CT in 26 (83.9%), and AFP assay in 12 (38.7%). In 4 patients, ultrasonography detected four recurrent nodules that CT missed. In 1 patient, two subphrenic nodules were detected with CT but not with ultrasonography. The specificity of US, CT, and AFP assay was 90.9%, 95.5%, and 93.2% respectively. Frequent follow-up study with ultrasonography in combination with CT and AFP assay should be recommended for the early detection of recurrent HCC. Ultrasonography is mandatory for the follow-up of patients with a prior hepatectomy for HCC.     

Characterization of SCCA-IgM as a biomarker of liver disease in an Asian cohort of patients

Viral hepatitis infection is a major global issue and a leading cause of liver disease and associated deaths. Over time, patients infected with hepatitis B (HBV) or C virus (HCV) develop cirrhosis and, eventually, hepatocellular carcinoma (HCC). For this reason, they need to be constantly monitored. Current Asian guidelines recommend the determination of serum alpha-fetoprotein (AFP) together with liver ultrasounds every six months to detect HCC nodules. However, both methods have several limitations, and other biomarkers have been studied for monitoring cirrhosis, including SCCA-IgM, an immune-complex formed by Squamous Cell Carcinoma Antigen and IgM. To date, SCCA-IgM has been validated as a novel biomarker for liver diseases only in European populations. The aim of our study was to analyze SCCA-IgM as a biomarker to monitor cirrhosis evolution in an Asian cohort of patients and to compare its performance to that of AFP. We analyzed the concentration of AFP and SCCA-IgM in serum samples obtained from a group of Asian adult patients with cirrhosis or HCC and a control group of patients admitted for gastrointestinal disorders. In untreated patients and similarly to AFP, SCCA-IgM levels were significantly higher in patients with cirrhosis compared to those with HCC. In addition, SCCA-IgM, but not AFP serological levels, were significantly lower in HCC patients who were treated with surgical resection compared to those who received a different therapy.     

人肝癌组织和外周血中甲胎蛋白基因片段扩增及临床应用

目的 研究外周血肝癌发生相关甲胎蛋白(AFP)基因在肝癌早期诊断和鉴别诊断中的价值。方法：从肝癌组织和肝病患者外周血中制备总RNA，经随机引物和逆转录酶作用合成cDNA，再以逆转录巢式聚合酶链反应(RT—PCR)扩增AFP基因，并分析其临床价值。结果 RT—巢式PCR扩增的AFP基因片段为159bp，与原设计一致；在20份肝癌及其癌周和远癌组织中，AFP基因阳性率分别为100％、65％和0％；肝癌患者外周血AFP基因检出率为53．7％，明显高于肝硬化、急、慢性肝炎和肝外肿瘤组患者(P＜0．01)；在Ⅰ、Ⅱ和Ⅲ期肝癌中AFP基因阳性率分别为33．3％、26．3％和71．8％；伴肝外转移者全数阳性；AFP＜50ng/ml肝癌AFP基因阳性率为50％，且与肝癌大小无关。结论 外周血AFP基因检测是肝癌诊断与鉴别诊断、肝外转移或术后复发的有用标志物。     

Evaluation of prothrombin induced by vitamin K absence,macrophage migration inhibitory factor and Golgi protein-73 versus alpha fetoprotein for hepatocellular carcinoma diagnosis and surveillance

Hepatocellular carcinoma (HCC) represents a challenging malignancy of worldwide importance. It is the third most common cause of cancer-related death globally as most patients present with unresectable disease. Alpha-fetoprotein (AFP) is the widely and solely used biomarker for HCC diagnosis; yet, its usefulness is hampered by low sensitivity and specificity. We aimed to identify more sensitive biomarkers for HCC diagnosis and a surveillance algorithm that may facilitate early detection of HCC. A total of 305 Egyptian and Saudi participants grouped as healthy controls, cancer controls, benign hepatic lesions, chronic viral hepatitis and HCC were included. Serum AFP, prothrombin induced by vitamin K absence-II (PIVKA-II), macrophage migration inhibitory factor (MIF) and Golgi protein-73 (GP-73) levels were quantitated by enzyme immunoassay. Significantly higher levels of GP-73 and PIVKA-II were detected in the HCC group than in all other groups, while MIF showed a highly significant increase in HCC from all groups except the cancer control group. The HCC group showed no significant difference between the studied biomarkers and the type of chronic viral hepatitis. On the basis of multiple ROC curve analyses, GP-73 and PIVKA-II showed the highest sensitivity and specificity for surveillance and diagnosis. In conclusion, PIVKA-II and GP-73 offer an effective approach for early HCC diagnosis and surveillance of high-risk groups with a higher accuracy than AFP. MIF may serve as a promising screening tumor marker for the detection of gastrointestinal tract (GIT) malignancy.     

Expression changes of serum LINC00941 and LINC00514 in HBV infection‐related liver diseases and their potential application values

BackgroundLong non‐coding RNAs (LncRNAs) are considered as potential diagnostic markers for a variety of tumors. Here, we aimed to explore the changes of LINC00941 and LINC00514 expression in hepatitis B virus (HBV) infection‐related liver disease and evaluate their application value in disease diagnosis.MethodsSerum levels of LINC00941 and LINC00514 were detected by qRT‐PCR. Potential diagnostic values were evaluated by receiver operating characteristic curve (ROC) analysis.ResultsSerum LINC00941 and LINC00514 levels were elevated in patients with chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) compared with controls. When distinguishing HCC from controls, serum LINC00941 and LINC00514 had diagnostic parameters of an AUC of 0.919 and 0.808, sensitivity of 85% and 90%, and specificity of 86.67% and 56.67%, which were higher than parameters for alpha fetal protein (AFP) (all p < 0.0001). When distinguishing HCC from LC, CHB, or LC from controls, the combined detection of LINC00941 or LINC00514 can significantly improve the accuracy of AFP test alone (all p < 0.05).ConclusionsLINC00941 and LINC00514 were increased in the serum of HBV infection‐associated liver diseases and might be independent markers for the detection of liver diseases.     

82例肝细胞癌患者高尔基体蛋白73的检出与分析

目的：通过定量检测肝细胞癌、慢性肝炎肝硬化患者及健康者血清中高尔基体蛋白73（GP73）和甲胎蛋白（AFP）水平,对比分析GP73与AFP的检出率,探讨GP73用于诊断肝细胞癌的临床意义。方法收集健康者、慢性肝炎肝硬化及肝细胞癌患者血清样本,分别采用酶联免疫吸附测定法和化学发光法检测GP73和 AFP。结果在肝细胞癌患者血清中,GP73检出率为75．61％,AFP检出率为40．24％,GP73明显高于AFP ,差异有统计学意义（P＜0．01）;慢性肝炎肝硬化患者GP73检出率为12．58％,AFP检出率为41．67％,GP73检出率明显低于 AFP ,差异有统计学意义（P＜0．01）;健康者GP73检出率为1．67％, AFP检出率为6．67％,两者比较差异无统计学意义（P＞0．05）。在健康者和慢性肝炎肝硬化患者中GP73特异度为93．42％, AFP特异度为77．78％;ROC曲线分析显示GP73和AFP的曲线下面积分别为0．9341和0．8066,GP73与AFP两者联合检测对肝细胞癌的检出率为87．80％。结论 G P73在健康者中检出率和水平极低,慢性肝炎肝硬化患者为12．58％,肝细胞癌患者高达75．61％。ROC曲线分析与检出率基本一致。GP73在肝细胞癌患者中检出率高,特异度强,是早期诊断肝细胞癌的首选标志物。联合GP73和AFP检测可以提高对肝细胞癌的早期诊断率。     

α-烯醇化酶在HBV相关肝细胞肝癌诊断中的应用价值

目的 通过检测乙型肝炎病毒(HBV)相关肝细胞肝癌(HCC)患者血清中α-烯醇化酶(ENO1)的浓度,探讨ENO1 作为肝癌诊断相关指标的可能性.方法 共纳入2018 年3 月至2019年9月肝病科、肝胆外科就诊的90例HCC患者、45例肝硬化(LC)患者、45例肝纤维化(LF)患者和45 例健康体检(NC)者.收集四...     

乙型病毒性肝炎肝硬化并肝脏畸胎瘤误诊为肝癌原因分析

目的提高乙型病毒性肝炎（乙肝）肝硬化并肝脏畸胎瘤诊断水平,减少误、漏诊。方法回顾分析1例乙肝肝硬化并肝脏畸胎瘤误诊为肝癌临床资料。结果患者以右上腹痛伴尿黄入院,经血清肝纤维化指标、肝炎病毒血清标志物检查诊断乙肝肝硬化,根据B超及CT检查显示肝右叶占位及甲胎蛋白（AFP）1320．00μg／L,诊断原发性肝癌。患者拒绝手术,经保肝、降酶及抗病毒治疗,肝功能及AFP改善,3个月后恢复正常。随访20个月,肝脏占位病变无变化,行手术治疗,经病理检查确诊肝脏畸胎瘤。结论乙肝肝硬化并肝脏占位伴AFP增高者,易误诊,条件许可情况下,应尽早手术确诊。     

Validation of the hepatocellular carcinoma early detection screening algorithm Doylestown and aMAP in a cohort of Chinese with cirrhosis

BackgroundPrevious studies have developed some blood‐based biomarker algorithms such as the Doylestown algorithm and aMAP score to improve the detection of Hepatocellular carcinoma (HCC). However, no one has studied the application of the Doylestown algorithm in the Chinese. Meanwhile, which of these two screening models is more suitable for people with liver cirrhosis remains to be investigated.MethodsIn this study, HCC surveillance was performed by radiographic imaging and testing for tumor markers every 6 months from August 21, 2018, to January 12, 2021. We conducted a retrospective study of 742 liver cirrhosis patients, and among them, 20 developed HCC during follow‐up. Samples from these patients at three follow‐up time points were tested to evaluate alpha‐fetoprotein (AFP), the Doylestown algorithm, and aMAP score.ResultsOverall, 521 liver cirrhosis patients underwent semiannual longitudinal follow‐up three times. Five patients were diagnosed with HCC within 0–6 months of the third follow‐up. We found that for these liver cirrhosis patients, the Doylestown algorithm had the highest accuracy for HCC detection, with areas under the receiver operating characteristic curve (AUCs) of 0.763, 0.801, and 0.867 for follow‐ups 1–3, respectively. Compared with AFP at 20 ng/ml, the Doylestown algorithm increased biomarker performance by 7.4%, 21%, and 13% for follow‐ups 1–3, respectively.ConclusionsOur findings show that the Doylestown algorithm performance appeared to be optimal for HCC early screening in the Chinese cirrhotic population when compared with the aMAP score and AFP at 20 ng/ml.     

原发性肝癌患者病毒标志物检测及介入治疗对HBV DNA的影响

目的研究乙型肝炎病毒DNA和血清标志物与原发性肝癌的关系以及介入治疗前后HBV DNA和肝功能的变化。方法对151例肝癌患者做HBV-m,HBV DNA和AFP测定,对14例肝癌病人介入前后测HBV DNA和肝功能。结果肝癌患者HBV总感染率为96.68%,以HBsAg、抗HBe、抗HBc3c项同时阳性模式(俗称小三阳)最多见,占53.64%(81/151),其次为HBsAg、HBeAg、抗HBc 3项同时阳性(俗称大三阳)占20.52%(31/151)。小三阳中HBV DNA阳性占74.07%(60/81);AFP阳性率63.6%(91/143),介入治疗引起肝功能损害加重,HBV DNA水平升高,前者有显著性差异,后者无显著性差异。结论HBV感染与肝癌发生密切相关,而且以HBsAg、抗HBe、抗HBc 3项同时阳性模式最多见,该模式中大部分患者HBV DNA处于复制活跃状态;介入治疗引起肝功能损害加重,对HBV DNA水平的影响应引起重视。     

Magnetic resonance of focal liver lesions in hepatic cirrhosis and chronic hepatitis.

Detection of focal liver nodules in patients with cirrhosis continues to be a radiologic challenge despite progressive advances in liver imaging in the past 2 decades. Patients with hepatic cirrhosis have a high predisposition to develop hepatocellular carcinoma (HCC), and the early detection and diagnosis of this tumor is very important because the most effective treatment is surgical resection, transplantation, or local ablation therapy when the tumor is small. Cirrhotic livers are mainly composed of fibrosis, together with a broad spectrum of focal nodular lesions ranging from regenerative nodules to premalignant dysplastic nodules to overt HCC. Awareness of such lesions and interpretation of imaging studies in these patients requires a critical review to detect subtle tumors, and a thorough understanding of the imaging appearance of the malignant and benign masses that can occur in the cirrhotic liver. Although the recent advances in liver imaging techniques, especially computed tomography (CT) and magnetic resonance (MR), have facilitated the detection and characterization of focal liver nodules in cirrhotic patients, discriminating between HCC and precancerous nodules remains problematic with all available imaging techniques. Nevertheless, MR imaging appears to have more potential than other imaging techniques in the study of cirrhotic patients and MR may be more appropriate than the other imaging modalities for the detection of small HCCs. In this article we review the imaging characteristics of nodular focal lesions that arise in cirrhotic livers, with special attention to MR imaging features.     

AFP-L3: a new generation of tumor marker for hepatocellular carcinoma.

BACKGROUND: Alpha-fetoprotein (AFP) from hepatocellular carcinoma (HCC) displays differential affinity to lectin Lens culinaris agglutinin (LCA) compared to that from chronic hepatitis/liver cirrhosis. According to their binding capability to LCA, total AFP can be separated into three different glycoforms, AFP-L1, AFP-L2, and AFP-L3. AFP-L1 is the non-LCA-bound fraction, which constitutes the major glycoform of AFP in serum of chronic hepatitis and liver cirrhosis. AFP-L3 is the LCA-bound fraction of AFP. It has been reported that malignant liver cells produce AFP-L3, even when HCC is at its early stages, and especially when the tumor mass is supplied by the hepatic artery. Clinical research has determined that AFP-L3 is a highly specific marker for HCC. The AFP-L3 can be detected in the serum of approximately 35% of the patients with small HCC (<2 cm). The AFP-L3-positive HCC has potential for rapid growth and early metastasis. Compared to imaging techniques, it has been shown to have 9-12 months of lead-time in early HCC recognition. Combined sensitivity of AFP-L3 for HCC is 56%, with a specificity of >95%. METHODS: Automated assay for measuring AFP-L3 has been developed and introduced in clinical use. The new automated method for measurement of ALP-L3 is based on liquid phase binding of the AFP-L3 glycoform with LCA and two specific monoclonal antibodies labeled with peroxidase and polysulfated tyrosine peptide, respectively. CONCLUSION: AFP-L3 is a new generation of tumor marker for HCC and yields useful information on HCC for clinical decision making.     

Early detection and characterization of hepatocellular carcinoma: value of imaging multistep human hepatocarcinogenesis

The method for early detection of hepatocellular carcinoma (HCC) has been well established in Japan, by means of regularly screening patients at risk for developing HCC by imaging and serological markers of tumor. The principal screening protocol includes performing ultrasonography (US) every 3 months and testing for tumor markers every month in patients at high risk for HCC. There has been another important issue of accurate characterization of nodular lesions found in cirrhotic liver. This problem has been solved by the development of imaging modalities such as US angiography with intra-arterial injection of CO(2), computed tomography during hepatic arteriography and computed tomography during arterial portography. It is most important to differentiate the typical hemodynamic patterns of a low-grade dysplastic nodule having arterial hypovascularity with portal perfusion preserved from those of HCC characterized by arterial hypervascularity with decreased portal perfusion. At present, these findings are easily obtained by contrast-enhanced phase invasion harmonic imaging, which is a noninvasive US technology.     

血浆Dickkopf同源物1检测对肝细胞癌的诊断价值

目的 探讨检测血浆Dickkopf同源物1(DKK1)对肝细胞癌(HCC)的诊断价值。方法 选取2014年11月～2015年12月南通市第三人民医院已确诊的HCC患者48例,肝硬化(LC)20例,慢性乙型肝炎(CHB)20例,选择排除其他慢性疾病的健康体检者(HC)20例,采用ELISA方法定量检测血浆中DKK1浓度,同时采用美国雅培i2000微粒子化学发光免疫分析仪检测其AFP。同时比较分析其ROC曲线及相关性。结果 HCC组DKK1水平均显著高于LC组、CHB组和HC组(Z=-4.132～-5.828,P均<0.001)。DKK1对HCC诊断价值的ROC曲线下面积为0.889,95%置信区间为0.831～0.947,DKK1诊断HCC最佳cutoff值为565 ng/L,其诊断灵敏度为93.8%,特异度为70%,AFP的ROC曲线下面积为0.759,95%置信区间为0.667～0.850。DKK1的AUC显著>AFP(Z=2.28,P=0.022)。DKK1和AFP两指标间无相关性(r=0.148,P=0.316),其中有21例AFP<20 μg/L而其DKK1>565 ng/L的诊断临界值。结论 检测血浆中DKK1可以作为AFP诊断HCC的有效补充,尤其是DKK1对AFP阴性HCC患者的早期诊断价值值得关注。     

甲胎蛋白、Ⅳ型胶原蛋白、甘胆酸、GPC3在乙型肝炎肝硬化与肝癌鉴别诊断的临床价值

目的 探讨血清甲胎蛋白(AFP)、Ⅳ型胶原蛋白(Ⅳ-C)、甘胆酸(CG)、磷脂酰肌醇蛋白聚糖3(GPC-3)水平在乙型肝炎肝硬化及原发性肝癌(PHC)鉴别诊断中的应用价值.方法 采用前瞻性队列研究,选择内蒙古医科大学附属医院2018年8月至2020年3月收治的55例PHC患者(PHC组),62例乙型肝炎肝硬化患者(肝硬...     

丙型肝炎病毒患者抗病毒干预持续应答后发生肝细胞肝癌的临床特征

[目的]研究丙型肝炎病毒(HCV)直接抗病毒药物(DAA)抗病毒干预获得持续病毒学应答(SVR)后发生肝细胞肝癌(HCC)患者的临床特征.[方法]纳入本院130例HCV感染患者作为研究对象,所有患者均接受HCV抗病毒治疗,记录SVR情况.出院后随访记录HCC发生率.根据是否发生HCC,将获得SVR的患者分为观察组(发生...     

去γ-羧基凝血酶原、甲胎蛋白在原发性肝细胞癌中的诊断价值

目的:探讨肿瘤标志物去γ-羧基凝血酶原(des-γ-carboxy prothrombin,DCP)、甲胎蛋白(alpha-fetoprotein,AFP)联合检测对原发性肝细胞癌(hepatocellular carcinoma,HCC)的诊断价值.方法:172例研究对象分为正常对照组25例、慢性肝炎组20例、肝硬化组51例及HCC组76例,酶联免疫法(ELISA)测定血清DCP浓度,电化学发光免疫法(ECLIA)测定血清AFP浓度,应用Logistic回归、ROC曲线对DCP、AFP、两者联合检测结果进行分析评价.结果:(1)正常对照组、慢性肝炎组、肝硬化组及HCC组DCP平均浓度分别为(17.72±9.59)、(26.12±12.64)、(37.45±18.26)和(806.71±639.79) mAU/mL,DCP浓度在4组间呈递增趋势(P＜0.05),且HCC组DCP浓度显著高于其他3组(P＜0.01).正常对照组、慢性肝炎组、肝硬化组及HCC组AFP平均浓度分别为(7.93±5.42)、(14.59±11.91)、(16.29±14.10)和(547.47±544.98) ng/mL,HCC组AFP浓度明显高于其他3组(P＜0.01).(2)DCP、AFP单独诊断HCC的ROC曲线下面积(AUROC)分别为0.891、0.813,DCP综合诊断效能优于AFP (P＜ 0.05);通过Logistic回归模型形成的联合预测因子(combining predictors,Comb)为分析指标,DCP、AFP联合检测时AUROC为0.932,优于DCP或AFP单独检测(P＜0.05).(3)通过ROC曲线确定DCP、AFP及Comb诊断HCC的最佳界定值分别为73.35 mAU/mL、35.38 ng/mL、0.28,此时具有较高的灵敏度和特异度.结论:DCP对我国HCC患者具有较好的诊断价值,运用Logistic回归、ROC曲线及诊断界定值综合分析DCP、AFP对HCC进行诊断,大大提高了诊断效能.