Changes of serum alpha-fetoprotein and alpha-fetoprotein-L3 after hepatectomy for hepatocellular carcinoma: prognostic significance

BACKGROUND: Alpha-fetoprotein (AFP) is the most established tumor marker of hepatocellular carcinoma (HCC), but one of its limitations is non-specificity. Many studies have demonstrated that alpha-fetoprotein-L3 (AFP-L3) is more specific than AFP in the early diagnosis and prognosis of HCC. However, there is a lack of knowledge about the post-hepatectomy profiles of serum AFP and AFP-L3 values in HCC patients. To identify the profiles after surgical resection of HCC, we analyzed the correlation between the profiles and postoperative HCC recurrence or survival, and evaluated their utility in predicting postoperative therapeutic efficacy and prognosis. METHODS: From August 2003 to December 2004, 318 patients with positive serum AFP who had received surgical resections were enrolled in this study. Preoperative and postoperative serum AFP and AFP-L3 levels were measured simultaneously and regularly, and their postoperative profiles during a long term follow-up were recorded and summarized. RESULTS: A high ratio of AFP-L3 to total AFP was shown to correlate with pathologic features of aggressiveness. The overall 1-, 3-, and 5-year recurrence rates of the whole series were 28% 57%, and 84%, and the overall survival rates were 86%, 61% and 33%, respectively. The changes of serum AFP and AFP-L3 after hepatectomy for HCC were classified into 3 groups (group A: AFP-L3 undetectable; group B: AFP-L3 <10%; and group C: AFP-L3 >10%). Patients with positive postoperative AFP-L3had significantly earlier recurrence than those with negative results. The overall survival was significantly shorter in the positive groups than in the groups negative for postoperative AFP-L3.CONCLUSION: Post-hepatectomy changes in serum AFP and AFP-L3 levels occurred in three distinct patterns, which were closely correlated with HCC recurrence and patient survival with different prognostic values.

The intracellular mechanism of alpha-fetoprotein promoting the proliferation of NIH 3T3 cells

AIM: The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS: The effect of AFP on the proliferation of NIH 3T3 cells was measured by incorporation of 3H-TdR. Receptor-binding assay of 125I-AFP was performed to detect the properties of AFP receptor in NIH 3T3 cells. The influences of AFP on the [cAMP]i and the activities of protein kinase A (PKA) were determined. Western blot was used to detect the change of K-ras P21 protein expression. RESULTS: The proliferation of NIH 3T3 cells treated with 0-80 mg/L of AFP was significantly enhanced. The Scatchard analysis indicated that there were two classes of binding sites with KD of 2.722 x 10(-9)M (Bmax=12810 sites per cell) and 8.931 x 10(-8)M (Bmax=119700 sites per cell) respectively. In the presence of AFP (20 mg/L), the content of cAMP and activities of PKA were significantly elevated . The level of K-ras P21 protein was upregulated by AFP at the concentration of 20 mg/L. The monoclonal antibody against AFP could reverse the effects of AFP on the cAMP content, PKA activity and the expression of K-ras p21 gene. CONCLUSION: The effect of AFP on the cell proliferation was achieved by binding its receptor to trigger the signal transduction pathway of cAMP-PKA and alter the expression of K- ras p21 gene.

DCP、AFP-L3和AFP在原发性肝细胞癌诊断中的价值

目的:探讨血清中脱γ一羧基凝血酶原(DCP)、甲胎蛋白异质体(AFP-L3)和甲胎蛋白(AFP)对原发性肝细胞癌(PHC)单独和联合诊断的意义,为PHC诊治提供一种新方法,以及对高危人群作筛选。方法:采集53例PHC、51例肝硬化、60例慢性肝炎和52例健康对照者的血清分别检测DCP、AFP-L3和AFP,并对其统计分析。结果:PHC患者的DCP、AFP-L3和AFP均显著高于肝硬化、慢性肝炎和健康对照者,DCP、AFP-L3和AFP在PHC组中的灵敏度分别为77.36%、69.8 1%和60.38%,特异性分别为89.57%、88.34%和77.91%。三者联检时,其诊断的敏感度可提高至94.34%。结论:DCP对PHC诊断具有较好的敏感度和特异性,联检DCP、AFP-L3和AFP可有效提高PHC尤其是AFP阴性PHC的诊断效率,对PHC的早期诊治具有一定指导意义。

256层CT动态增强扫描联合血清甲胎蛋白异质体比率、高尔基体蛋白73对乙肝相关性肝细胞癌的诊断价值

目的探讨256层CT动态增强扫描联合血清甲胎蛋白异质体(alpha-fetoprotein-L3,AFP-L3)比率、高尔基体蛋白73(Golgi protein 73,GP73)对乙肝相关性肝癌的诊断价值。方法将2021年1月至2021年6月入住空军军医大学唐都医院的乙型病毒性肝炎相关性肝细胞癌(hepatocellular carcinoma,HCC)患者58例(HCC组)和良性肝病患者63例(良性肝病组)纳入研究,检测患者血清AFP、AFP-L3%和GP73水平,利用256层CT动态增强扫描技术,对患者行上腹部CT扫描。分析比较两组患者的CT影像表现,分别探讨单独应用CT扫描、肿瘤标志物检测及联合运用两种技术诊断乙型病毒性肝炎相关性HCC的价值。结果HCC组的AFP-L3%、GP73浓度明显高于良性肝病组,差异均有统计学意义(t=9.38,5.99,均P<0.01);CT扫描、AFP-L3%、GP73浓度联合检测的ROC曲线下面积最大。CT扫描诊断HCC的灵敏度为87.93%,特异度为93.65%,准确率为90.91%;AFP-L3%诊断HCC的cut-off值为9.31%,诊断灵敏度为81.03%,特异度为87.30%,准确率为84.29%;GP73诊断HCC的cut-off值为105.62 ng/mL,诊断灵敏度为72.41%,特异度为82.54%,准确率为77.69%;CT扫描、AFP-L3%、GP73浓度联合检测的灵敏度为91.38%,特异度为93.65%,准确率为92.56%。结论联合运用CT动态增强扫描、血清AFP-L3%、GP73浓度检测对乙型病毒性肝炎相关性肝细胞癌诊断的灵敏度和准确率较运用单一技术均有所提高,联合运用这几种指标对乙型病毒性肝炎相关性HCC的准确诊断具有重要的临床价值。

GP73、AFP-L3和TGFβ1联合检测在肝细胞癌早期诊断中的临床价值

目的探讨高尔基体糖蛋白73(GP73)、甲胎蛋白异质体-L3(AFP-L3)和转化生长因子β1(TGFβ1)联合检测在肝细胞癌(HCC)早期诊断中的临床价值。方法选取健康对照组48例,乙型肝炎组42例,肝炎后肝硬化组50例,HCC组58例。对四组测试对象分别进行GP73、AFP-L3、TGFβ1水平检测,并对结果进行分析比较。结果 (1)不同组别间GP73、AFP-L3、TGFβ1平均水平差异具有统计学意义(P<0.05);(2)三指标联合检测,阳性检出率达到96.55%,高于两两指标联合检测和各指标单独检测。结论 (1)GP73、AFP-L3、TGFβ1均可作为肝癌早期诊断血清标志物;(2)与传统肝癌标志物AFP比较,AFP-L3具有较高的敏感度和特异性,且在良性、恶性肝脏疾病的鉴别诊断中具有重要作用,是一个较好的肝癌诊断血清标志物;(3)三指标联合检测后明显提高了对肝癌的检出率,有较好的应用价值。

Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma

Alpha-fetoprotein(AFP)is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma(HCC)in combination with ultrasound and other imaging modalities.Its utility is limited because of both low sensitivity and specificity,and discrepancies among the different methods of measurements.Moreover,its accuracy varies according to patient characteristics and the AFP cut-off values used.Combination of AFP with novel biomarkers such as AFP-L3,Golgi specific membrane protein(GP73)and des-gamma-carboxyprothrombin significantly improved its accuracy in detecting HCC.Increased AFP level could also signify severity of hepatic destruction and subsequent regeneration and is commonly observed in patients with acute and chronic liver conditions and cirrhosis.Hereditary and other non-hepatic disorders can also cause AFP elevation.

血清FER、AFP-L3联合检测诊断肝细胞癌的价值分析

目的探讨血清铁蛋白(FER)、甲胎蛋白异质体-L3(AFP-L3)联合检测诊断肝细胞癌的价值。方法采用病例对照研究方式,将该院就诊的45例肝细胞癌患者纳入观察组,选取40例肝硬化患者作为对照组A,43例慢性肝炎患者作为对照组B及45例健康的体检者作为健康对照组。分别检测血清中FER及AFP-L3水平,评估单一指标及联合指标诊断肝细胞癌的效果。结果观察组FER水平分别为308.74(193.22,531.96)ng/mL、15.29(9.11,37.36)μg/L,对照组A分别为159.34(57.45,432.93)ng/mL、0.65(0.17,2.18)μg/L,对照组B分别为229.20(72.04,379.99)ng/mL、0.78(0.15,2.15)μg/L,健康对照组分别为161.19(58.09,226.24)ng/mL、0.62(0.60,0.64)μg/L;观察组的FER、AFP-L3水平均显著高于其他组,差异均有统计学意义(P<0.05);FER诊断肝细胞癌时曲线下面积(AUC)为0.685,AFP-L3的AUC为0.943,均低于联合检测时的0.967且联合检测时灵敏度高达93.3%。结论肝细胞癌患者的血清FER、AFP-L3水平异常,临床可联合FER及AFP-L3进行疾病诊断以提高诊断效能。

甲胎蛋白及其异质体、磷脂酰肌醇蛋白聚糖3和基质金属蛋白酶2联合检测在肝细胞癌中的诊断价值

目的检测血清中甲胎蛋白(AFP)及其异质体(AFP-L3)、磷脂酰肌醇蛋白聚糖3(GPC3)和基质金属蛋白酶2(MMP2)的表达水平,探讨四项指标的联合检测对HCC的诊断价值。方法选取2019年12月至2020年12月于成都市公共卫生临床医疗中心住院的60例肝细胞癌患者为肝癌组,均经肝组织学检查确诊。60例肝硬化患者为肝硬化组,60例慢性乙型肝炎患者为慢性乙肝组,诊断符合防治指南。选择同期体检的60例健康者作为对照组。使用化学发光法及酶联免疫双抗体夹心法分别检测外周血清AFP及AFP-L3、GPC3、MMP2的水平。统计分析各组研究对象血清标志物的差异,计算联合检测的诊断效率。结果肝癌组的血清AFP、AFP-L3和GPC3、MMP2水平均明显高于慢性乙肝组、肝硬化组及对照组(M=122.3μg/L、88.33μg/L、53.45pg/ml、701.3μg/L;H=125.8、167.5、209.4、210.4;均P<0.05)。4项指标联合检测的诊断准确率为89.3%,灵敏度与特异度分别为84.87%与84.59%,其曲线下面积(AUC)为0.905,均高于单项检测,差异有统计学意义(均P<0.05)。结论AFP及AFP-L3、GPC3和MMP2均为HCC的危险因素,其联合检测可以提高HCC的阳性检出率,有助于其高危患者肿瘤的早期诊断、治疗,延长患者生存时间,提高生存率。

新型标志物AFP-L3和PIVKAⅡ在肝癌诊断中的价值评估

目的 探讨甲胎蛋白异质体L3(alpha-fetoprotein variants L3,AFP-L3)和维生素K缺乏或拮抗剂-Ⅱ诱导的蛋白质(protein induced by vitamin K absence or antagonist Ⅱ,PIVKAⅡ)在肝癌诊断中的的价值。方法 收集2019年1月至2022年1月期间青岛市第六人民医院收治的3 066例患有慢性肝脏疾病患者作为研究对象。比较AFP-L3、PIVKAⅡ、CK65、CK30、TK1在肝炎、肝硬化以及肝癌间的水平差异,评估特异性、敏感度,应用受试者工作特征曲线(receiver operating characteristic,ROC)曲线评估生物标志物及提出最优截断点。结果 AFP-L3和PIVKA在肝硬化组中表达高于肝炎组(P <0.000 1),CK65、CK30和TK在肝硬化组中表达低于肝炎组(P <0.001)。肝癌组中AFP-L3、CK65、CK30和PIVKA表达显著高于肝硬化组(P <0.000 1),TK在肝癌组中的表达低于肝硬化组(P> 0.05)。在纳入研究的5种生物标志物中,AFP-L3具有最高的特异度(0.89),PIVKAⅡ具有最高的灵敏度(0.62),且联合应用AFP-L3和PIVKAⅡ灵敏度达到0.70,特异度达到0.81,有相较于单个标志物更优的表现。ROC曲线分析表明PIVKAⅡ具有更高的诊断价值(24)。结论 在肝癌筛查中AFP-L3比PIVKAⅡ特异性高,联合AFP-L3和PIVKAⅡ诊断可其在肝癌中的诊断价值。

甲胎蛋白异质体和甲胎蛋白信使核糖核酸用于诊断肝细胞癌

目的:探讨联合检测血清肿瘤标志物甲胎蛋白(AFP)异质体(AFP-L3)和甲胎蛋白信使核糖核酸(AFPmRNA)诊断肝细胞癌及评估肝癌预后的价值。方法:对2005年4月—2005年7月收治的82例肝细胞癌(HCC)、11例慢性乙型肝炎肝硬化合并门脉高压和19例肝脏良性肿瘤患者,应用酶联吸附法及荧光定量反转录-聚合酶链反应(RT-PCR)联合检测AFP-L3和AFPmRNA水平,对比其阳性率。结果:AFP-L3和AFPmRNA联合检测阳性率可达87.6%,较单独检测AFP、AFP-L3、AFP-mRNA的阳性率(分别为69.5%、81.7%、36.6%)高,差异有统计学意义;术前、术后联合检测AFP-L3和AFPmRNA均阳性患者的术后3年生存率较低。结论:术前联合检测APF-L3和AFPmRNA可提高HCC,尤其是AFP阴性HCC的诊断率,而术后联合检测对评估HCC的预后有一定的指导意义。

Development and in vitro study of a bi-specific magnetic resonance imaging molecular probe for hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new strategies to enhance specificity and help early diagnosis of HCC.However,the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3,which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors<1 cm(MHCC).We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis.AIM To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level.METHODS A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3(UAG)was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle(USPIO).At the same time,the singly labeled probes of anti-AFP-USPIO(UA)and anti-GPC3-USPIO(UG)and non-targeted USPIO(U)were also prepared for comparison.The physical characterization including morphology(transmission electron microscopy),hydrodynamic size,and zeta potential(dynamic light scattering)was conducted for each of the probes.The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3.First,AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry.Then,the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI(T2-weighted and T2-map)with a 3.0 Tesla clinical MR scanner.RESULTS Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes.The iron Prussian blue staining and quantitative T2-map MRI analysis showed that,compared with UA,UG,and U,the uptake of double antigen-targeted UAG probe demonstrated a 23.3%(vs UA),15.4%(vs UG),and 57.3%(vs U)increased Prussian stained cell percentage and a 14.93%(vs UA),9.38%(vs UG),and 15.3%(vs U)reduction of T2 relaxation time,respectively.Such bi-specific probe might have the potential to overcome tumor heterogeneity.Meanwhile,the coupling of two antibodies did not influence the magnetic performance of USPIO,and the relatively small hydrodynamic size(59.60±1.87 nm)of double antibodyconjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo,as they are slowly phagocytosed by macrophages.CONCLUSION The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly-or non-targeted USPIO,paving the way for in vivo translation to further evaluate its clinical potential.

Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models

AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD).

Bi-specific T1 positive-contrast-enhanced magnetic resonance imaging molecular probe for hepatocellular carcinoma in an orthotopic mouse model

BACKGROUND Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related mortality.HCC-targeted magnetic resonance imaging(MRI)is an effective noninvasive diagnostic method that involves targeting clinically-related HCC biomarkers,such as alpha-fetoprotein(AFP)or glypican-3(GPC3),with iron oxide nanoparticles.However,in vivo studies of HCC-targeted MRI utilize single-target iron oxide nanoprobes as negative(T2)contrast agents,which might weaken their future clinical applications due to tumor heterogeneity and negative MRI contrast.Ultra-small superparamagnetic iron oxide(USPIO)nanoparticles(approximately 5 nm)are potential optimal positive(T1)contrast agents.We previously verified the efficiency of AFP/GPC3-double-antibody-labeled iron oxide MR molecular probe in vitro.AIM To validate the effectiveness of a bi-specific probe in vivo for enhancing T1-weighted positive contrast to diagnose the early-stage HCC.METHODS The single-and double-antibody-conjugated 5-nm USPIO probes,including antiAFP-USPIO(UA),anti-GPC3-USPIO(UG),and anti-AFP-USPIO-anti-GPC3(UAG),were synthesized.T1-and T2-weighted MRI were performed on day 10 after establishment of the orthotopic HCC mouse model.Following intravenous injection of U,UA,UG,and UAG probes,T1-and T2-weighted images were obtained at 12,12,and 32 h post-injection.At the end of scanning,mice were euthanized,and a histologic analysis was performed on tumor samples.RESULTS T1-and T2-weighted MRI showed that absolute tumor-to-background ratios in UAG-treated HCC mice peaked at 24 h post-injection,with the T1-and T2-weighted signals increasing by 46.7%and decreasing by 11.1%,respectively,relative to pre-injection levels.Additionally,T1-weighted contrast in the UAG-treated group at 24 h post-injection was enhanced 1.52-,2.64-,and 4.38-fold compared to those observed for single-targeted anti-GPC3-USPIO,anti-AFP-USPIO,and nontargeted USPIO probes,respectively.Comparison of U-,UA-,UG-,and UAG-treated tumor sections revealed that UAG-treated mice exhibited increased stained regions compared to those observed in UG-or UA-treated mice.CONCLUSION The bi-specific T1-positive contrast-enhanced MRI probe(UAG)for HCC demonstrated increased specificity and sensitivity to diagnose early-stage HCC irrespective of tumor size and/or heterogeneity.

原发性肝癌预后不良的危险因素及其预后预测价值分析

目的分析原发性肝癌(HCC)预后不良的危险因素及其预后预测价值。方法回顾性分析2018年3月至2020年3月本院收治的100例HCC患者的临床资料,患者均采取肝动脉化疗栓塞治疗,行高尔基体蛋白73(GP73)、甲胎蛋白异质体-L3(AFP-L3)、甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)水平检测。分析患者术后1年预后情况,采用单因素、多因素Logistic回归分析HCC患者术后1年死亡的危险因素,绘制ROC曲线分析GP73、AFP-L3、AFP、AFU对HCC患者术后1年死亡的预测价值。结果100例HCC患者中,死亡15例,生存85例。死亡患者年龄≥60岁、微血管侵犯、淋巴结转移、无肿瘤包膜比例及GP73、AFP-L3、AFP、AFU水平均高于生存患者,差异有统计学意义(P<0.05);死亡与生存患者性别、病理分型比较差异无统计学意义。ROC曲线分析结果显示,GP73、AFP-L3、AFP、AFU预测HCC患者术后1年死亡的AUC分别为0.829、0.781、0.811、0.894,均具有一定预测价值。多因素Logistic回归分析结果显示,年龄≥60岁、微血管侵犯、淋巴结转移、无肿瘤包膜、GP73≥154.550μg/L、AFP-L3≥8.255%、AFP≥58.085μg/L、AFU≥40.335μg/L为HCC患者术后1年死亡的危险因素(OR>1,P<0.05)。结论高龄、微血管侵犯、淋巴结转移、无肿瘤包膜及GP73、AFP-L3、AFP、AFU高水平可能导致HCC患者术后预后不良,临床应根据上述因素制定相关预防措施,以改善患者预后。

三个血清学标志物联合检测用于肝癌诊断的临床意义

目的通过对原发性肝癌以及良性肝病患者样本进行甲胎蛋白(AFP)、甲胎蛋白异质体(AFP-L3)以及高尔基体蛋白73(GP73)3种血清学标志物的检测,研究3种血清学肿瘤标志物指标联合检测用于诊断肝癌的临床意义。方法采用酶联免疫法检测GP73,用化学发光法检测AFP,AFP检测为阳性的再采用亲和吸附离心法检测AFP-L3。结果 AFP、AFP-L3、GP73联合用于检测可以使肝癌诊断的敏感性提高到96.72%(118/122),将肝癌诊断的特异性提高到96.05%(73/76)。结论将AFP、AFP-L3以及GP73用于联合检测,可以有效地提高目前临床检测肝癌的敏感性以及特异性。

Expert consensus on the role of hematological markers in the earlyclinical screening of hepatocellular carcinoma

The disease burden of hepatocellular carcinoma (HCC) in China is heavy, and the prognosis is stillunfavourable. Therefore, early screening of high-risk groups of HCC through simple methods is the key toachieving early diagnosis and treatment and improving survival. At present, alpha-fetoprotein and otherhematological tests are still the main methods in the early screening of HCC, but the sensitivity andspecificity are limited, and the risk of missed diagnosis is high. In recent years, with the continuousdevelopment of science and technology, the improvement of traditional detection methods and theemergence of novel markers such as methylated deoxyribonucleic acid and microRNA have brought hopefor further improving the sensitivity and specificity of early HCC screening. This consensus summarizesthe research progress of traditional and new hematological test methods and puts forward expertguidance on the role of hematological markers in the early screening of HCC to provide a basis forimproving the prevention and control level in China.