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。     

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...     

血清甲胎蛋白、Dickkopf相关蛋白1、细胞骨架蛋白4 联合检测对肝细胞癌的诊断价值

目的探讨血清甲胎蛋白(AFP)、分泌型蛋白Dickkopf-1(DKK1)、细胞骨架蛋白4(CKAP4)联合检测对肝细胞癌(HCC)的临床诊断价值。方法纳入2013年1月至2017年12月苏州大学附属第一医院收治的122例HCC患者(76例早期患者)、152例肝硬化患者、105例慢性乙型肝炎患者,同期从门诊体检部选取健康体检者101例,作为健康对照组。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验;计数资料多组间比较采用χ~2检验。用二分类变量logistic回归进行分析,产生新变量(预测概率),并对各单项指标、预测概率进行受试者工作特征(ROC)曲线分析,评估单项及联合检测的ROC曲线下面积(AUC)、敏感度及特异度。结果 HCC组患者的血清AFP、DKK1、CKAP4水平均明显高于肝硬化、慢性乙型肝炎和健康对照组,差异均有统计学意义(F值分别为121. 618、84. 559、91. 769,P值均0. 001)。由AFP、DKK1、CKAP4联合形成的新变量判断HCC的AUC为0. 967[95%置信区间(95%CI):0. 950～0. 984],敏感度为0. 869,特异度为0. 980,显著高于各项指标单独检测(P值均0. 05)。新变量判断早期HCC的AUC为0. 965(95%CI:0. 942～0. 988),敏感度为0. 868,特异度为0. 980,显著高于各项指标单独检测(P值均0. 05)。结论血清AFP、DKK1、CKAP4联合检测提高了HCC诊断的准确度、敏感度及特异度,对HCC高危人群的筛查及早期诊断有重要的临床参考价值。     

寡糖链检测对HBV相关性肝细胞癌的诊断价值

目的 探讨寡糖链检测在乙型肝炎病毒(HBV)相关性肝细胞癌(HCC)诊断中的临床价值.方法 收集2017年2月至2018年8月就诊于南京医科大学第一附属医院并符合纳入与排除标准的435名受试者的血清及相关资料,共分为五组,其中健康对照组(HC)80例、慢性乙型肝炎(CHB)组105例、乙型肝炎肝硬化(LC)组60例、其...     

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。     

血清甲胎蛋白联合碱性磷酸酶评分对可切除肝细胞癌患者预后的预测价值

目的 建立一个基于术前血清甲胎蛋白(AFP)与碱性磷酸酶(ALP)的评分系统,并探讨其在可切除肝细胞癌(HCC)患者中的预后价值。方法 回顾性纳入2016年1月—2019年8月在天津市第一中心医院以肝切除术作为初始治疗的154例HCC患者。通过受试者工作特征(ROC)曲线确定血清AFP与ALP的最佳临界值。采用Kaplan-Meier曲线和Log-rank检验进行生存分析,以评估AFP联合ALP评分与HCC患者无病生存(DFS)的关系。通过单因素及多因素Cox回归分析确定HCC患者的独立预后因素。符合正态分布的计量资料组间比较采用独立样本t检验;不符合正态分布的计量资料组间比较采用Mann-Whitney U检验。计数资料组间比较采用χ²检验。结果 ROC曲线显示,血清AFP预测DFS的最佳临界值为250.0 ng/mL,曲线下面积(AUC)为0.674 (95%CI:0.580～0.767);血清ALP的最佳临界值为95.5 U/L, AUC为0.745 (95%CI:0.652～0.838)。生存分析结果展示术前血清高AFP(≥250.0 ng/mL)和高AL...     

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...     

甲胎蛋白应答在肝细胞癌治疗中的预后价值

肝细胞癌（HCC）是最常见的肝脏恶性肿瘤。因其恶性程度高、预后差,准确评估患者的治疗效果及预后情况至关重要。尽管目前影像学是肝癌预后评估的标准方法,但其仍存在诸多局限性。甲胎蛋白是重要的肝癌肿瘤标志物,广泛的应用于肝癌的筛查、诊断及预后评价。总结了甲胎蛋白应答在评判肝癌患者预后的相关文献。整体上,甲胎蛋白应答在肝癌患者接受射频消融、肝动脉化疗栓塞、钇90放射性栓塞、索拉菲尼等分子靶向药物、全身化疗、肝动脉灌注化疗或同步放化疗等治疗后具有良好的预后价值。     

AFP-L3含量测定在肝癌诊治中的意义

目的探讨甲胎蛋白异质体3（AFP-L3）检测在肝细胞癌（HCC）诊治中的临床意义。方法采用ELISA法测定112例肝病患者血清标本人小扁豆素结合型甲胎蛋白（AFP）/AFP-L3的含量。结果 HCC患者的AFP-L3阳性率为81.7%,高于肝硬化组（18.2%）、肝脏良性肿瘤组（10.5%）;术后AFP-L3持续阳性的HCC患者1、2、3 a生存率分别为77.3%、45.5%、22.7%,而AFP-L3转阴的HCC患者1、2、3 a生存率分别为75.6%、53.7%、41.5%,两组3 a生存率有显著差异。结论测定AFP-L3对AFP阳性时的良、恶性肝病的鉴别及HCC的早期诊断、预后判断具有重要意义。     

The preoperative positivity for serum hepatitis B e antigen did not affect overall survival after curative resection of hepatitis B virus-related hepatocellular carcinoma

Background and Aim:  Previous studies have reported different risk factors for early and late intrahepatic recurrence after resection of hepatocellular carcinoma (HCC). However, the prognostic significance of the risk factors for early and late recurrence has not been clarified.
Methods:  A total of 190 Hepatitis B surface antigen-positive patients who received curative resection for HCC were reviewed. We investigated prognostic factors for disease-free and overall survival after resection, and further analyzed the relationship between significant prognostic factors and risk factors for early (≤14 months) and late (>14 months) intrahepatic recurrence.
Results:  The 5-year disease-free and overall survival rates were 43.9% and 71.5%, respectively. In multivariate analysis, adverse prognostic factors for disease-free survival were presence of serum HBeAg, perioperative transfusion, and the presence of portal vein invasion (PVI) and/or intrahepatic metastasis (IM). Multivariate analysis revealed that overall survival was associated with ICG R15, serum albumin, Edmondson–Steiner grade, and the presence of PVI and/or IM. Independent risk factors for early intrahepatic recurrence were perioperative transfusion and PVI and/or IM, whereas positivity for HBeAg was the only risk factor for late recurrence. In addition, post-recurrence survival in patients with late intrahepatic recurrence was completely comparable to that of patients who never experienced recurrence.
Conclusions:  The presence of serum HBeAg, the risk factor for late intrahepatic recurrence did not affect overall survival after resection because late recurrence was relatively well controlled by current available treatments. To further improve long-term surgical outcomes, effective treatment and preventive methods for early intrahepatic recurrence should be investigated.     

Combined serum hepatoma-specific alpha-fetoprotein and circulating alpha-fetoprotein-mRNA in diagnosis of hepatocellular carcinoma

Introduction Hepatocellular carcinoma (HCC) is a major health problem throughout the world.[1-3] It ranks the fifth in frequency worldwideamong all malignancies and causes one million deaths annually,[4, 5] yet its incidence is increasing steadily in various countries.[6-8] The carcinogenesis of HCC is a multi-factorial, multi-step and complex process. Perhaps hepatitis B virus (HBV) infection is merely a carcinogenic factor, and is not related to the growth, infiltration and metastasis of…     

Clinical features of hepatitis B virus-related hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major cause of cancer death,and chronic hepatitis B is a serious worldwide problem.The epidemiology of HCC is distinctive.Hepatitis B virus (HBV) plays a major role in hepatocarcinogenesis.Prevention of HBV-related HCC is a key issue in current hepatology.This paper describes the prevention and clinical features of HBVrelated HCC,along with a short review of the disease.     

Ultrasonography and alpha-fetoprotein in diagnosis of hepatocellular carcinoma in cirrhosis

The accuracy of ultrasound (US) and alpha-fetoprotein (AFP) in the diagnosis of hepatocellular carcinoma (HCC) in 363 patients with cirrhosis (C) and a clinical suspicion of HCC was assessed. The ultrasonographic patterns of HCC and their relationship with AFP values were analyzed. Echographic patterns were distributed as follows: 47 patients had sonodense lesions; 30 patients had hypoechoic lesions; 47 had mixed-pattern lesions, and in four patients focal dilated intrahepatic bile ducts were demonstrated. The sensitivity of US was 90%; specificity was 93.3%. Serum AFP level 500 ng/ml (RIA) was the first clue to the diagnosis in 71 patients (48.6%); specificity was 100%. In 28 patients AFP levels became significantly elevated during follow-up after US detection of HCC. No relationship between echo pattern and serum AFP levels was demonstrated. An algorithm for diagnosis of HCC is proposed.     

Association between serum hepatocyte growth factor and survival in untreated hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is a common hepatic malignancy worldwide. Its nature of rapid growth results in a grave prognosis. Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, responsible for their proliferation. The aim of the present study was to investigate the prognostic roles of serum HGF in untreated HCC patients.Methods Fifty-five patients with inoperable HCC were studied. The diagnosis of HCC was based on either liver histopathology or imaging evidence of a liver mass, together with elevated serum alpha-fetoprotein. Serum HGF levels of the patients, at the time of diagnosis, were compared to those of 28 healthy controls. All patients received only palliative treatments and were followed up until they died. Comparison of survival curves between patients with a serum HGF level of 1.0ng/ml or more and those with lower serum HGF was performed, using the log-rank test. Data values are expressed as means and SD.Results Fifty-one men and four women with inoperable HCC were recruited. The mean age was 54.15 ± 15.34 years. The serum HGF levels in the inoperable HCC patients were significantly higher than those in the controls (0.58 ± 0.43 vs 0.14 ± 0.04ng/ml; P < 0.001). The patients mean survival time was 5.28 ± 6.73 months (range, 0.1–33 months). Serum HGF levels exhibited a negative correlation with the survival time (P = 0.032). In addition, HCC patients with serum HGF levels of 1.0ng/ml or more had a shorter survival time than the other HCC patients (P = 0.0025).Conclusions Patients with inoperable HCC had higher levels of serum HGF than the healthy controls, and serum HGF was negatively correlated with the survival time. Serum HGF levels of 1.0ng/ml or more in HCC patients are suggestive of a grave prognosis, indicating that HGF plays important and active roles in the disease progression. The detailed mechanisms need to be further investigated.     

Negative hepatitis B envelope antigen predicts intrahepatic recurrence in hepatitis B virus-related hepatocellular carcinoma after ablation therapy

Background and Aim: Patients with persistently active hepatitis B virus (HBV) replication are at high risk for progression to liver cirrhosis and hepatocellular carcinoma (HCC). The influence of the viral load of HBV on intrahepatic recurrence after local ablation therapy in patients with HBV‐related HCC has not been elucidated. We aimed to evaluate predictors of intrahepatic recurrence and clarify the correlation between viral load and intrahepatic recurrence after percutaneous ablation. Methods: Patients with HBV‐related, solitary HCC undergoing radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), between October 2004 and December 2008 were prospectively enrolled. Statistical analyses were performed using the Kaplan–Meier method and Cox regression model to identify risk factors for intrahepatic recurrence. Results: A total of 145 patients (male, 81.4%; mean age, 55.3 years) were included. Ninety patients (62.1%) had serum HBV DNA ≥ 2000 IU/mL. The median follow‐up duration was 28.9 months (range, 12.0–57.0) and 63 patients (43.4%) experienced intrahepatic tumor recurrence. Multivariate analysis indicated that seropositivity for hepatitis B envelope antigen (HBeAg) was an independent negative predictor of intrahepatic recurrence (hazard ratio, 0.473; P = 0.026) and late (≥ 1 year) recurrence (HR, 0.288; P = 0.012). The serum alpha fetoprotein (AFP) level also significantly predicted late recurrence (HR, 1.001; P = 0.005). However, neither the ablation method nor serum HBV DNA titers were correlated with intrahepatic recurrence. Conclusions: These findings show that HBeAg‐negativity and serum AFP levels were associated with late intrahepatic recurrence of HCC, implicating HBeAg‐negativity as a risk factor for de novo recurrence after percutaneous ablation in HBV‐related HCC.     

Autophagy and microRNA in hepatitis B virus-related hepatocellular carcinoma

Approximately 350 million people worldwide are chronically infected by hepatitis B virus (HBV). HBV causes severe liver diseases including cirrhosis and hepatocellular carcinoma (HCC). In about 25% of affected patients, HBV infection proceeds to HCC. Therefore, the mechanisms by which HBV affects the host cell to promote viral replication and its pathogenesis have been the subject of intensive research efforts. Emerging evidence indicates that both autophagy and microRNAs (miRNAs) are involved in HBV replication and HBV-related hepatocarcinogenesis. In this review, we summarize how HBV induces autophagy, the role of autophagy in HBV infection, and HBV-related tumorigenesis. We further discuss the emerging roles of miRNAs in HBV infection and how HBV affects miRNAs biogenesis. The accumulating knowledge pertaining to autophagy and miRNAs in HBV replication and its pathogenesis may lead to the development of novel strategies against HBV infection and HBV-related HCC tumorigenesis.