AFP-L3 Research Articles

Surface-enhanced Raman scattering from an electromagnetic induced transparency substrate for the determination of hepatocellular carcinoma.

Surface-enhanced Raman scattering (SERS) is a powerful analytical method that is especially suitable for the detection of protein molecules. Detection sensitivity of SERS is directly related to the enhancement factor of the substrate, which is dependent on the strength of a local surface electric field generated by surface plasmonic resonance from substrate. In this study, an electromagnetic induced transparency like (EIT-like) metamaterial was used as the SERS substrate. The corresponding plasmonic resonance structure not only produces stronger optical near field but also reduces the spectral line broadening due to radiation damping. This is very beneficial for SERS process, which is strongly dependent on electric field intensity, to improve the sensitivity of SERS detection. Compared with the single resonance mode substrate, the enhancement factor for SERS with the double-mode substrate was increased by an order of magnitude. The obtained EIT-like substrate was used as a SERS-active substrate to detect Lens culinaris agglutinin (LCA)-reactive fraction of AFP (AFP-L3), a hepatocellular carcinoma (HCC)-specific maker. Experimental results are in good agreement with the clinical diagnosis, which demonstrates the potential application of metamaterials in the SERS-based diagnosis and biosensing.

The Performance of AFP, AFP-3, DCP as Biomarkers for Detection of Hepatocellular Carcinoma (HCC): A Phase 3 Biomarker Study in the United States

α-fetoprotein (AFP), AFP Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP) in combination or in GALAD (Gender, Age, AFP-L3, AFP, and DCP) were tested for hepatocellular carcinoma (HCC) surveillance in retrospective cohort and case-control studies. However, there is a paucity of prospective data and no phase III biomarker studies from North American populations. We conducted a prospective specimen collection, retrospective blinded evaluation (PRoBE) cohort study in patients with cirrhosis enrolled in a 6-monthly surveillance with liver imaging and AFP. Blood samples were prospectively collected every 6 months and analyzed in a retrospective blinded fashion. True positive rate (TPR) and false positive rate (FPR) for any or early HCC were calculated within 6, 12, and 24 months of HCC diagnosis based on published thresholds for biomarkers individually, in combination and in GALAD and Hepatocellular Carcinoma Early Detection Screening (HES) scores. We calculated the area under the receiver operating curve and estimated TPR based on an optimal threshold at a fixed FPR of 10%. The analysis was conducted in a cohort of 534 patients; 50 developed HCC (68% early) and 484 controls with negative imaging. GALAD had the highest TPR (63.6%, 73.8%, and 71.4% for all HCC, and 53.8%, 63.3%, and 61.8 % for early HCC within 6, 12, and 24 months, respectively) but an FPR of 21.5% to 22.9%. However, there were no differences in the area under the receiver operating curve among GALAD, HES, AFP-L3, or DCP. At a fixed 10% FPR, TPR for GALAD dropped (42.4%, 45.2%, and 46.9%) and was not different from HES (36.4%, 40.5%, and 40.8%) or AFP-L3 alone (39.4%, 45.2%, and 44.9%). In a prospective cohort phase III biomarker study, GALAD was associated with a considerable improvement in sensitivity for HCC detection but an increase in false-positive results. GALAD performance was modest and not different from AFP-L3 alone or HES.

The diagnostic value of AFP, AFP L3 and PIVKA II in hepatocellular carcinoma outcome of cirrhosis of the liver HBV and HCV etiology

Hepatocellular carcinoma (HCC) is the third largest cause of death among all cancer cases in the world.Moreover, in most cases, it develops against the background of viral hepatitis of the liver. I should be noted, and the fact that the detection of the later stages of the forecast it usually unfavorable.This study focuses on AFP, AFP L 3, and PIVKA II as oncological markers of HCC in patients with chronic viral hepatitis. It was found that the use of the combination of PIVKA II and AFP increases the sensitivity by 16.6% compared with the use of AFP alone, which is comparable with the results of all three-tumor markers.

DCP and AFP-L3 Are Complementary to AFP in Predicting High-Risk Explant Features: Results of a Prospective Study

Among patients with hepatocellular carcinoma (HCC), elevated α-fetoprotein (AFP) has been shown to predict waitlist dropout, high-risk histopathologic features, and inferior post-liver transplant (LT) outcome.1,2 Nevertheless, many patients with HCC have a normal AFP and yet still experience waitlist dropout or post-LT recurrence.2 Because of the degree of imprecision associated with AFP, there is a quest for other biomarkers that may be complementary to or better than AFP in predicting prognosis in LT. Lectin-reactive AFP (AFP-L3) and des-gamma-carboxyprothrombin (DCP) are biomarkers that have been used in conjunction with AFP as HCC surveillance or diagnostic tools.3,4 However, the utility of these biomarkers in LT for HCC is not established.

Associations of Serum Tumor Biomarkers with Integrated Genomic and Clinical Characteristics of Hepatocellular Carcinoma

Introduction: Serum α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-γ-carboxy­pro­thrombin (DCP) are useful biomarkers of hepatocellular carcinoma (HCC). However, associations among molecular characteristics and serum biomarkers are unclear. We analyzed RNA expression and DNA variant data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) to examine their associations with serum biomarker levels and clinical data. Methods: From 371 TCGA-LIHC patients, we selected 91 seen at 3 institutions in Korea and the USA and measured AFP, AFP-L3, and DCP from preoperatively obtained serum. We conducted an integrative clinical and molecular analysis, focusing on biomarkers, and validated the findings with the remaining 280 patients in the TCGA-LIHC cohort. Results: Patients were categorized into 4 subgroups: elevated AFP or AFP-L3 alone (↑AFP&L3), elevated DCP alone (↑DCP), elevation of all 3 biomarkers (elevated levels of all 3 biomarkers [↑All]), and reference range values for all biomarkers (RR). CTNNB1 variants were frequently observed in ↑DCP patients (53.8%) and RR patients (38.5%), but ↑DCP patients with a CTNNB1 variant had worse survival than RR patients. TP53 sequence variants were associated with ↑AFP (30.8%) and ↑DCP (30.8%). The Wnt-β-catenin signaling pathway was activated in the ↑AFP&L3, whereas liver-related Wnt signaling was activated in the RR. TGF-β and VEGF signaling were activated in ↑AFP&L3, whereas dysregulated bile acid and fatty acid metabolism were dominant in ↑DCP. We validated these findings by showing similar results between the test cohort and the remainder of the TCGA-LIHC cohort. Conclusions: Serum AFP, AFP-L3, and DCP levels can help predict variants in the genetic profile of HCC, especially for TP53 and CTNNB1. These findings may facilitate development of an evidence-based approach to treatment.

The diagnostic value of AFP, AFP L3 and PIVKA II in hepatocellular carcinoma outcome of cirrhosis of the liver HBV and HCV etiology

Hepatocellular carcinoma (HCC) is the third largest cause of death among all cancer cases in the world.Moreover, in most cases, it develops against the background of viral hepatitis of the liver. I should be noted, and the fact that the detection of the later stages of the forecast it usually unfavorable.This study focuses on AFP, AFP L 3, and PIVKA II as oncological markers of HCC in patients with chronic viral hepatitis. It was found that the use of the combination of PIVKA II and AFP increases the sensitivity by 16.6% compared with the use of AFP alone, which is comparable with the results of all three-tumor markers.

Evaluation of the Combined Application of AFP, AFP-L3%, and DCP for Hepatocellular Carcinoma Diagnosis: A Meta-analysis.

The role of α-fetoprotein (AFP) in the surveillance and diagnosis of hepatocellular carcinoma (HCC) has been questioned in recent years due to its low sensitivity and specificity. In addition to AFP, several new serum biomarkers, such as lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-gamma-carboxy prothrombin (DCP), have also been identified as useful HCC serological markers. However, the exact diagnostic value of the combinations of these biomarkers for detecting HCC in patients with liver disease remains unclear. Thus, we performed the current meta-analysis to assess performance of AFP+AFP-L3%+DCP for diagnosing HCC. Studies were systematically searched in PubMed, Embase, the Cochrane Library, CNKI, and WanFang Data databases. After full-text evaluation, 13 studies from 11 articles focusing on the combination of the three serum biomarkers for HCC detection were enrolled. Random-effects models were used due to the presence of heterogeneity. The pooled sensitivity and specificity for AFP+AFP-L3%+DCP were 88% and 79%, respectively. The area under the summary receiver operating characteristic (sROC) curve was 0.91, and the diagnostic odds ratio (DOR) was 28.33 (95% CI 16.78-47.83). Subgroup analysis showed that the pooled sensitivity and specificity of AFP+AFP-L3%+DCP in the diagnosis of HCC versus cirrhosis patients were 0.81 and 0.82, respectively. In conclusion, the combination of AFP, AFP-L3%, and DCP may prove to be useful in the diagnosis and screening of HCC.

Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommends that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) consider HCC surveillance. NITs include the fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US), which is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US, or if an US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, the lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and the protein induced by the absence of vitamin K or antagonist-II (PIVKA-II), can help identify a high risk of HCC in NAFLD patients. Innovative parameters, including a Mac-2 binding protein glycated isomer, type IV collagen 7S, free apoptosis inhibitor of the macrophage, and a combination of single nucleoside polymorphisms, are expected to be established. Considering the large size of the NAFLD population, optimal screening tests must meet several criteria, including high sensitivity, cost effectiveness, and availability.

The Early Decline of α-Fetoprotein and Des-γ-Carboxy Prothrombin Predicts the Response of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients

Introduction: Molecular targeting drugs are recommended as second-line treatment for intrahepatic advanced hepatocellular carcinoma (HCC). However, in Asia, hepatic arterial infusion chemotherapy (HAIC) is also considered as a second-line treatment because it improves the survival of responders. The aim of this study was to predict responders and non-responders to HAIC with low-dose cisplatin plus 5-fluorouracil (LFP) using tumor markers. Objective and Methods: The data of 47 patients who received LFP for the first time in our hospital were analyzed retrospectively. We evaluated the association between treatment response by Response Evaluation Criteria in Solid Tumors and the changing ratio of the serum concentration of α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-γ-carboxy prothrombin (DCP) 2 weeks after LFP initiation. Results: The number of patients showing a complete response (CR), a partial response (PR), stable disease (SD), and progressive disease (PD) was 0 (0%), 20 (43%), 18 (38%), and 9 (19%), respectively. The AFP ratio showed significant positive correlations for PR vs. SD (p = 0.004) and PR vs. PD (p = 0.003). The DCP ratio correlated significantly for PR vs. SD (p = 0.02). The optimal cutoff values for responders were 0.79 for the AFP ratio and 0.53 for the DCP ratio. Prediction using both or either cutoff value showed 93% sensitivity, 53% specificity, a 94% negative predictive value, and a 57% positive predictive value. Conclusion: Optimal cutoff values for AFP and DCP ratios enable prediction of nonresponders to HAIC with LFP. This simple and early assessment method allows the use of HAIC and molecular targeting drugs for HCC treatment.

Role of GALAD serological model in the clinical diagnosis of primary hepatocellular carcinoma

Objective To explore the value of GALAD model, including gender, age, AFP, AFP-L3 and DCP in diagnosis of primary hepatocellular carcinoma and prediction of microvascular invasion (MVI). Methods Using retrospective study method, 5 919 patients with primary hepatocellular carcinoma (HCC) who received radical operation from January 2015 to December 2018 in Eastern Hepatobiliary Surgery Hospital were enrolled into study group. At the same time, 1 745 patients with benign liver diseases (BLDs) were enrolled into control group. The concentration of DCP was detected by Lumipulse G1200 automatic immune analyzer, and the concentration of AFP was detected by Cobas e601 automatic immune analyzer. AFP-L3 was detected by affinity adsorption centrifugation. The non-parametric Mann Whitney test was used to compare the difference between two groups. The chi square test was used to compare the rates. The diagnostic value of single serological marker and GALAD model for primary hepatocellular carcinoma was analyzed. The predictive effect of GALAD model on MVI of primary hepatocellular carcinoma was evaluated. Results Compared with single serum marker, the diagnostic value of GALAD model is higher. When the cutoff value is -0.33, the diagnostic sensitivity, specificity and accuracy reach to 91.9% (5 440/5 919), 86.8% (1 515/1 745) and 90.7% (6 955/7 664), respectively. The area under the curve can reach 0.960 [95%CI (0.955-0.964)]. Compared with no MVI (MO) group, the value of GALAD model in MVI low-risk group (M1), MVI high-risk group (M2) and MVI (M1+2) were significantly higher (Z values were-12.517, -22.883, -21.655, P<0.05), Galad model predicts MVI (M2) in high risk group,AUC was 0.717 [95%CI (0.701-0.733)] (M0 ratio M2). Conclusion GALAD model has better diagnostic performance in primary hepatocellular carcinoma and has certain predictive value for microvascular invasion. Key words: Carcinoma, hepatocellular; Liver neoplasms; Neoplasm invasiveness; Microvessels; alpha-Fetoproteins; Prothrombin

Research progress on the molecular biomarkers for patients with hepatocellular carcinoma recurrence after surgery

Tumor recurrence is the main factor affecting the postoperative prognosis of hepatocellular carcinoma. The forecast of tumor recurrence by monitoring biomarker can effectively improve the prognosis of such disease. To improve the detection rate of early cancer recurrence can be achieved by detecting the level of the alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin (DCP), or combined detection. In recent years, the researches on the miRNA and Long Noncoding RNAs (LncRNA), which are key regulators in the upstream of signal pathways, could provide a new way for HCC recurrence monitoring. The combined detection of biomarkers in different control levels, maybe is the effective measure to improve the tumor recurrence detection rate, and is also the focus of the further research. Key words: Hepatocellular carcinoma; Tumor recurrence; Molecular biomarker

Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma.

Alpha-fetoprotein (AFP), Lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). This study compared the diagnostic values of AFP, AFP-L3, and PIVKA-II individually and in combination to find the best biomarker or biomarker panel.Seventy-nine patients with newly diagnosed HCC and 77 non-HCC control patients with liver cirrhosis were enrolled. AFP, AFP-L3, and PIVKA-II were measured in the same serum samples using microchip capillary electrophoresis and a liquid-phase binding assay on an automatic analyzer. Receiver-operating characteristic curve analyses were also applied to all combinations of the markers.When the 3 biomarkers were analyzed individually, AFP showed the largest area under the receiver-operating characteristic curve (AUC) (0.751). For combinations of the biomarkers, the AUC was highest (0.765) for "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL." The combination of "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL and AFP-L3 > 10%" had worse sensitivity and lower AUC (P = 0.001). The highest AUC of a single biomarker was highest for AFP and of a combination was "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL," with this also being the case when the cut-off value of AFP and AFP-L3 was changed.Alpha-fetoprotein showed the best diagnostic performance as a single biomarker for HCC. The diagnostic value of AFP was improved by combining it with PIVKA-II, but adding AFP-L3 did not contribute to the ability to distinguish between HCC and non-HCC liver cirrhosis. These findings were not altered when the cut-off value of AFP and AFP-L3 was changed.

The detection value of serum alpha-L-fucosidase and alpha fetoprotein 3 in primary hepatocellular carcinoma

Objective To study the detection value of serum alpha-L-fucosidase(AFU) and alpha fetoprotein 3(AFP-L3) in primary hepatocellular carcinoma(HCC). Methods 100 patients with primary HCC were enrolled as HCC group, 54 cases without HCC were selected as non HCC group, 100 healthy persons were selected as healthy group.Serum AFU and AFP-L3 levels in three groups were determined.The serum AFU was measured by the chemical colorimetry, and the AFP-L3 level was determined by chemiluminescence immunoassay. Results The serum levels of AFU in HCC group, non HCC group and healthy group were (71.61±3.01)U/L, (11.06±2.15)U/L, (8.54±1.28)U/L.The serum levels of AFP-L3 in HCC group, non HCC group and healthy group were (30.14±2.93)%, (3.27±0.83)%, (2.77±0.62)%.The serum levels of AFU and AFP-L3 in HCC group were significantly higher than those in non HCC group and healthy group (t=13.172, 9.770, 16.036, 7.160, all P 0.05). The positive rates of AFU were 87.00%, 9.26% and 3.00% in HCC group, non HCC group and healthy group.The positive rate of AFU in HCC group was significantly higher than that in non HCC group and healthy group (χ2=34.06, 57.62, all P 0.05). The positive rates of AFP-L3 were 89.00%, 7.41% and 2.00% in HCC group, non HCC group and healthy group.The positive rate of AFP-L3 in HCC group was significantly higher than that in non HCC group and healthy group (χ2=41.06, 77.62, all P 0.05). There were no significant differences in serum tumor diameter about AFU, AFP-L3(t=0.167, 0.579, 0.201, 0.601, all P>0.05), and there were significant differences about TNM stage, lymph node metastasis, and tumor thrombus (t=6.156, 9.105, 10.161, 8.120, 9.770, 12.821, all P<0.05). Conclusion Serum AFU and AFP-L3 can not only help the diagnosis of primary liver cancer, but also can determine the prognosis of patients. Key words: Liver neoplasms; Alpha-L-fucosidase; Alpha fetoprotein 3

A Chemiluminescent Protein Microarray Method for Determining the Seroglycoid Fucosylation Index.

The Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) is widely used to screen for hepatocellular carcinoma (HCC) in Japan and China. We developed a chemiluminescent protein microarray for determining the AFP-L3/AFP index (the ratio of AFP-L3 to total AFP, AFP-L3%) by fixing AFP-specific antibodies and Lens culinaris lectin on aldehyde-coated glass slides. Serum samples were tested for AFP using an enzyme-linked immunosorbent assay (ELISA) to validate the microarray. AFP-L3 was detected using Hotgen Biotech glycosyl capture spin column pretreatment technology and ELISA. When the AFP cut-off value was set to 20 ng/ml, the protein microarray displayed 89.74% sensitivity and 100% specificity for HCC diagnosis, and the ELISA displayed 87.17% sensitivity and 100% specificity. When the AFP-L3% cut-off value was set to 0.1, the protein microarray displayed 56.41% sensitivity and 100% specificity for HCC diagnosis, and the ELISA displayed 53.84% sensitivity and 100% specificity. The ROC curve for the HCC diagnosis showed that the AFP area under the ROC curve (AUC = 0.996; 95% CI: 0.986–1.005) was much higher than that of AFP-L3 (AUC = 0.857; 95% CI: 0.769–0.94) and AFP-L3% (AUC = 0.827; CI: 0.730–0.924). The microarray assay used in this study is a highly sensitive, accurate, and efficient assay for the determination of the AFP-L3%.

Assessment of serum GP73, AFP-L3, AFP and AFU detection in the diagnosis of hepatocellular carcinoma

Objective Explore the clinical application values of Golgi Protein 73 (GP73), AFP variants (AFP-L3) , Alpha fetoprotein (AFP)and α-l-Fucosidase (AFU) detection in the diagnosis of hepatocellular carcinoma (HCC). Methods From January of 2013 to June of 2014, 84 case of HCC Patients(HCC group) who presented at interventional department; 64 case of cirrhotic patients(liver cirrhosis group), 86 case of chronic hepatitis patients(chronic hepatitis group) and 120 healthy people (normal control group) were selected from Shanghai Tongren Hospital. GP73 was detected by the enzyme-linked immunosorbent assay (ELISA), AFP-L3 was isolated with ACSC, AFP and AFP-L3 were detected with ECLIA and calculated the percentage content of AFP-L3 (AFP-L3%), AFU was detected with enzyme kinetic method. Adopted the SPSS 19.0 statistical software for data analysis. The rank sum test was used in the multi group comparison; the chi square test was used in the comparison group. Results Serum levels of GP73, AFP-L3, AFP and AFU in HCC group were 202.1 μg/L, 9.5%, 68.3 μg/L, 33.2 μg/L respectively. Their difference from those of the normal control group(69.0 μg/L, 2.5%, 4.5 μg/L, 24.2 μg/L) was of statistical significance (U was 1126.59, 204.67, 1247.68, 564.08, respectively, all P 0.05) Sensitivity of GP73 and AFP in individual inspection was 95.24%, significantly higher than that of AFU, AFP-L3. Specificity of AFP-L3 was 94.81% respectively, with an accuracy of 85.88% respectively. Specificity and accuracy of the allied detection of GP73, AFP-L3, AFP and AFU for HCC diagnosis were 98.52% and 84.75% respectively. Conclusions The allied combination of serum GP73, AFP-L3, AFP and AFU makes up for the insufficient clinical applications of individual serum markers. It is of great clinical significance to improve the diagnosis of HCC.(Chin J Lab Med, 2016, 39: 262-266) Key words: Golgi apparatus; alpha-Fetoproteins; alpha-L-fucosidase; Liver neoplasms; Diagnosis

Expression and clinical value of Pokemon in hepatocellular carcinoma

Objective To detect the serum expression level of Pokemon and explore its clinical value combines with AFP, AFP-L3 or DCP in hepatocellular carcinoma (HCC). Methods In this study, the serum levels of Pokemon, AFP, AFP-L3 and DCP in 30 patients with HCC, 34 patients with benign liver diseases and 30 healthy controls were examined by enzyme-linked immunosorbent assay. Then, the clinical significance of Pokemon expression level was analyzed. In the end, the diagnostic evaluation of four serum biomarker alone detection was used to analyze the sensitivity, specificity, the area under the curve and Youden index in the diagnosis of HCC. Results The serum expression level of Pokemon in patients with HCC was (22.63±6.82)ng/ml, which was significantly higher than that in the group with benign liver diseases and healthy controls [(3.54±1.26)ng/ml, t=8.594, P<0.001; (1.95±0.57)ng/ml, t=10.021, P<0.001]. The expression level of Pokemon in HCC patients was correlated to tumor size (t=2.678, P=0.021) and TNM stag (t=2.578, P=0.034). The serum expression levels of AFP, AFP-L3 and DCP in patients with HCC were (774.56±96.52)ng/ml, (26.37±2.54)ng/ml and (93.49±30.45)mAU/ml, which were significantly higher than those in the group with benign liver diseases [(22.21±3.57)ng/ml, (7.05±2.71)ng/ml, (34.68±10.13)mAU/ml] and healthy controls [(14.65±4.45)ng/ml, (3.84±1.09)ng/ml, (25.87±9.01)mAU/ml, F=58.46, P=0.000; F=12.47, P=0.000; F=23.41, P=0.000]. The sensitivity and specificity of Pokemon, AFP, AFP-L3, DCP in the diagnosis of HCC were 84.6% and 87.5%, 52.5% and 78.9%, 95.0% and 80.0%, 77.1% and 87.5%, respectively. Conclusion The enhanced Pokemon serum level, with its sensitivity and specificity higher than AFP, points out Pokemon may be a potentially useful biomarker to diagnose HCC. Key words: Liver neoplasms; Enzyme-linked immunosorbent assay; Pokemon protein

Optimization of risk-predicting models for hepatitis B virus-related hepatocellular carcinoma

Objective The present study aimed to optimize the established predictive models (REACH-B scoring model) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods The hepatitis B surface antigen (HBsAg) positive (> 6 months) patients who were firstly admitted in the Liver Center of First Affiliated Hospital, Fujian Medical University between Oct 1st 2004 and May 1st 2014 were selected as the subjects and divided into two groups, namely, the case group (HCC group) and the control group (non-HCC group). Clinical data of all the subjects were retrospectively collected and analyzed. Receiver operating characteristic curves were used to evaluate the predictive values of the various models. Results To predict the development of HBV-related HCC within 3 years, a total of 627 patients (151 HCC cases and 476 non-HCC controls) were enrolled. Area under curve (AUC) of HBV-related HCC (REACH-B) scoring model was 0.78 (95%CI: 0.74-0.82), with the sensitivity of 73.00% and specificity of 78.70% in predicting 3-year risk of HCC occurrence. By combining alpha-fetoprotein (AFP) and REACH-B, the R-AFP scoring model was constructed. The AUC increased to 0.80 (95%CI: 0.76-0.83, Z=2.50, P=0.01), with the sensitivity of 71.03% and specificity of 79.13% in predicting 3-year HCC development. By combining AFP isoform 3 (AFP-L3%) and REACH-B, the R-AFP-L3% scoring model was constructed. The AUC further increased to 0.83 (95%CI: 0.80-0.87, Z=2.45, P=0.01), with the sensitivity of 75.01% and specificity of 79.32% in predicting 3-year HCC development. To predict the development of HBV-related HCC within 5 years, a total of 159 (65 HCC cases and 94 non-HCC controls) were enrolled. The AUC of REACH-B scoring model was 0.79 (95%CI: 0.72-0.87), with the sensitivity of 73.60% and specificity of 75.43%. The R-AFP scoring model had an AUC of 0.84 (95%CI: 0.77-0.90, Z=2.70, P=0.006), with the sensitivity of 83.12% and specificity of 77.89%. Conclusion Combination of AFP or AFP-L3% may optimize the predictive values of REACH-B scoring model in predicting 3-year and 5-years risks of developing HBV-related HCC. Key words: Hepatitis B virus; Carcinoma, hepatocellular; alpha-Fetoproteins; Forecasting

Highly sensitive alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxyprothrombin for hepatocellular carcinoma detection.

Hepatocellular carcinoma (HCC) develops with high incidence in patients with chronic liver disease (CLD), and particularly in those with cirrhosis. Currently, diagnosis and surveillance are mainly based on imaging methods. The aim of this study was to evaluate the diagnostic accuracy of highly sensitive measurement of α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-γ-carboxyprothrombin (DCP) alone and in combination, for HCC detection. In addition, a recently proposed statistical model, including these three biomarkers plus sex and age, the GALAD model, was applied. In a total of 98 patients (44 CLD patients without HCC [23 men, 21 women; mean age, 53.2 ± 13.4 years] and 54 patients with HCC [45 men, nine women; 69.5 ± 9.8 years]), AFP, AFP-L3 and DCP levels were determined using a highly sensitive assay on an μTASWako i30 immuno-analyzer. Areas under the curve (AUC), sensitivity and specificity were calculated and compared to assess diagnostic performance of the HCC biomarkers and of the GALAD model. AFP, AFP-L3 and DCP serum levels were significantly elevated in HCC compared with CLD patients (P < 0.0001). AUC values were 0.891, 0.867 and 0.870, respectively. The combination of the three biomarkers resulted in an AUC of 0.947, whereas the GALAD model showed an AUC of 0.976 with a difference between AUC values of 0.029 (P = 0.028). The combination of AFP, AFP-L3 and DCP is superior to a single biomarker in HCC detection. Furthermore, GALAD model performance is significantly higher than simple combination of these three biomarkers.

Current trends and recent advances in diagnosis, therapy, and prevention of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), des- carboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

Su1486 Fucosylated AFP (AFP-L3) a Significant Prognostic Factor to Predict Early Recurrence Beyond Milan Criteria After Initial Resection for Small and Single HCC

Su1486 Fucosylated AFP (AFP-L3) a Significant Prognostic Factor to Predict Early Recurrence Beyond Milan Criteria After Initial Resection for Small and Single HCC