Dataset Information

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

ABSTRACT: The role of ?-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.

SUBMITTER: Wang X

PROVIDER: S-EPMC7519464 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Wang Xueying X Zhang Yangyu Y Yang Na N He Hua H Tao Xuerong X Kou Changgui C Jiang Jing J

BioMed research international 20200917

The role of <i>α</i>-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 ...[more]

PMID: 33015170

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Project description:Background & aimsα-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.MethodsWe 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%.ResultsThe 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%).ConclusionsIn 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.

Project description:OBJECTIVE:Hepatocellular carcinoma (HCC) has become a pressing health problem facing the world today due to its high morbidity, high mortality, and late discovery. As a diagnostic criteria of HCC, the exact threshold of Alpha-fetoprotein (AFP) is controversial. Therefore, this study was aimed to systematically estimate the performance of AFP in diagnosing HCC and to clarify its optimal threshold. METHODS:Medline and Embase databases were searched for articles indexed up to November 2019. English language studies were included if both the sensitivity and specificity of AFP in the diagnosis of HCC were provided. The basic information and accuracy data included in the studies were extracted. Combined estimates for sensitivity and specificity were statistically analyzed by random-effects model using MetaDisc 1.4 and Stata 15.0 software at the prespecified threshold of 400 ng/mL, 200 ng/mL, and the range of 20-100 ng/mL. The optimal threshold was evaluated by the area under curve (AUC) of the summary receiver operating characteristic (SROC). RESULTS:We retrieved 29,828 articles and included 59 studies and 1 review with a total of 11,731 HCC cases confirmed by histomorphology and 21,972 control cases without HCC. The included studies showed an overall judgment of at risk of bias. Four studies with AFP threshold of 400 ng/mL showed the summary sensitivity and specificity of 0.32 (95%CI 0.31-0.34) and 0.99 (95%CI 0.98-0.99), respectively. Four studies with AFP threshold of 200 ng/mL showed the summary sensitivity and specificity of 0.49 (95%CI 0.47-0.50) and 0.98 (95%CI 0.97-0.99), respectively. Forty-six studies with AFP threshold of 20-100 ng/mL showed the summary sensitivity and specificity of 0.61 (95%CI 0.60-0.62) and 0.86 (95%CI 0.86-0.87), respectively. The AUC of SROC and Q index of 400 ng/mL threshold were 0.9368 and 0.8734, respectively, which were significantly higher than those in 200 ng/mL threshold (0.9311 and 0.8664, respectively) and higher than those in 20-100 ng/mL threshold (0.8330 and 0.7654, respectively). Furthermore, similar result that favored 400 ng/mL were shown in the threshold in terms of AFP combined with ultrasound. CONCLUSION:AFP levels in serum showed good accuracy in HCC diagnosis, and the threshold of AFP with 400 ng/mL was better than that of 200 ng/mL in terms of sensitivity and specificity no matter AFP is used alone or combined with ultrasound.

Project description:Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is prevalent worldwide. Despite its limitations, serum alpha-fetoprotein (AFP) remains the most widely-used biomarker for the diagnosis of HCC. This study aimed to assess whether measurement of peripheral plasma Dickkopf-1 (DKK1) and Tie2-expressing monocytes (TEMs) could overcome the limitations of AFP and improve the diagnostic accuracy of HCC.Plasma DKK1 level and the percentage of TEMs in peripheral CD14+CD16+ monocytes from HCC patients (n = 82), HBV-related liver cirrhosis (LC) patients (n = 29), chronic hepatitis B (CHB) infected patients (n = 28) and healthy volunteers (n = 31) were analyzed by ELISA and flow cytometry. Receiver operating characteristic (ROC) curves were used to analyze a single biomarker, or a combination of two or three biomarkers. Univariate and multivariate analyses were performed to assess the significance of each marker in prediction of HCC and AFP-negative HCC from LC patients.The percentage of TEMs in peripheral CD14+CD16+ monocytes and plasma level of DKK1 in HCC group were significantly higher than those in LC, CHB and healthy control groups (all P-values <0.05). The percentage of TEMs alone was also significantly higher in AFP-negative HCC group than that in LC, CHB and healthy control groups (all P-values <0.05). Plasma DKK1 level alone could not distinguish between AFP-negative HCC and LC patients. ROC curves showed that the optimal diagnostic cutoff value was 550.93 ng/L for DKK1 and 4.95% for TEMs. There was no significant difference in AUC of DKK1, TEMs and AFP in HCC diagnosis between the four groups (all P>0.05). A combination of DKK1, TEMs and AFP measurements increased the AUC for HCC diagnosis as compared with either marker alone (0.833; 95%CI 0.768-0.886). The AUC for TEMs was 0.692 (95% CI 0.564-0.819) in differentiating AFP-negative HCC from LC, with a sensitivity of 80.0% and a specificity of 65.52%. Only TEMs prevailed as a significant predictor for AFP-negative HCC differentiating from LC patients in univariate and multivariate analyses (P = 0.016, P = 0.023).TEMs and DKK1 may prove to be potential complementary biomarkers for AFP in the diagnosis of HCC. TEMs rather than DKK1 could serve as a complementary biomarker for AFP in the differential diagnosis of AFP-negative HCC versus LC patients.

Dataset Information

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

Publications

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

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