Usefulness of Highly Sensitive AFP-L3 and DCP in Surveillance for Hepatocellular Carcinoma in Patients with a Normal Alpha-Fetoprotein (original) (raw)
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International Journal of Clinical Biochemistry and Research, 2023
Background: Serum AFP has a poor clinical performance values especially when it comes to dealing with the early and AFP-negative diagnostic of HCC. This study aimed to assess the contribution of AFP in the diagnosis of HCC. Materials and Methods: A total of 95 subjects were in a prospective observational study by consecutive enrolment and divided into two groups. The first group was made up with subjects in whom the diagnosis of HCC had been retained the second was the control group which was free of HCC. AFP levels were performed by electrochemiluminescence immunoassay on the cobas e411®. Data were captured in Excel and analyzed by Ri386 version 4.1.2 binary for macOS 10.13. Results: Log of AFP median of AFP in HCC subjects was significantly greater than in non HCC subjects 6.91 ng/mL versus 1.43 ng/mL, Wilcoxon p-value < 0.001. At the cutoff of 200 ng/mL, the clinical performances showed an acceptable sensitivity 97.1% CI 95% [93.7-100] but a poor specificity 73,8% CI 95% [64.9-82.6] and out of the 34 cases of HCC, one case (2.9%) was AFP-negative HCC. Conclusion: Our data show an acceptable sensitivity but a weak specificity of AFP as a biomarker for HCC at a cutoff 200 ng/mL. This suggests that AFP should be used with other biomarkers, mainly for the early and AFP-negative HCC diagnosis. This is an Open Access (OA) journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
Journal of Gastroenterology and Hepatology, 2008
Background and Aim: Hepatocellular carcinoma (HCC) is a common complication in patients with chronic viral hepatitis. Detection of HCC at an early stage is critical for a favorable clinical outcome. The study aim was to: (i) compare the levels of des-gcarboxyprothrombin (DCP), a-fetoprotein (AFP) and AFP-L3 in HCC patients and in chronic viral hepatitis patients without HCC; (ii) define the level of each tumor marker with the best sensitivity and specificity for HCC diagnosis; and (iii) to correlate the levels of these markers with respect to size and tumor burden. Methods: Two hundred and forty patients with either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection were studied. These included 144 with HCC, 47 with chronic hepatitis (fibrosis stage I-III on liver biopsy) and 49 with cirrhosis. Results: Levels of DCP, AFP and AFP L-3 were significantly higher in patients with HCC than in those without HCC (P Յ 0.0001). Receiver-operating curves (ROC) indicated that the cut-off value with the best sensitivity and specificity for each test was Ն84 mAU/mL for DCP, Ն25 ng/mL for AFP and Ն10% for AFP-L3. The sensitivity, specificity and positive predictive value (PPV) for DCP was 87%, 85% and 86.8%, for AFP 69%, 87% and 69.8%, and for AFP-L3 56%, 90% and 56.1%, respectively. DCP levels were below the ROC cut-off in all patients without HCC. In patients with single lesions, there was a direct correlation of DCP to tumor size. High levels of AFP correlated with diffuse type of HCC. All three markers were significantly elevated in the presence of metastatic HCC. No advantage was observed by combining two or three markers for HCC diagnosis. Conclusion: DCP had the highest sensitivity and PPV for HCC diagnosis, had a direct correlation with tumor size, and was not elevated in any patients without HCC. DCP should be used as the main serum test for HCC detection.
Alpha Fetoprotein; Useful as Screening Test for Hepatocellular Carcinoma Due to Chronic Hepatitis C
THE PROFESSIONAL MEDICAL JOURNAL
ORIGINAL PROF-3690 ABSTRACT… BACKGROUND: Hepatocellular carcinoma (HCC) is a primary tumor of the liver, which develops in the setting of chronic liver disease, particularly in patients with chronic hepatitis B and C in almost 80% patients. Although there are no specific screening tests for diagnosis of HCC but alpha-fetoprotein (AFP) and abdominal ultrasound are commonly used. AFP >400 ng/ml is considered diagnostic for HCC. Objective: The objective of study was to validate the use of alphafetoprotein as screening test for HCC due to chronic HCV. Study Design: Observational cross-sectional. Period: March 2014 to August 2016. Setting: Aziz Bhatti Shaheed Teaching Hospital Gujrat. Materials and Methods: 134 patients aged >35 years having liver cirrhosis due to chronic HCV and diagnosed with HCC using biphasic CT scan were included and were followed for 1 year. Serum AFP was divided in 3 categories and a value < 20ng/ml-normal, 20-399 ng/ml-elevated and >400ng/ml-diagnostic of HCC. Liver nodules size and site was noted and divided in 4 categories. Severity of liver disease was calculated using Child Pugh Score. Analysis was done using SPSS 20.0. Results: AFP is diagnostic (>400 ng/ml) in only 29.9% of patients with sensitivity of 43.3% at cut off value of 400 ng/ml and is significantly associated with severity of liver disease. Conclusion: AFP cannot be used as screening test for HCC in patients with cirrhosis due to chronic HCV. Abdominal ultrasound should be used for early detection of HCC due to chronic hepatitis C.
Alpha1-acid glycoprotein as potential biomarker for alpha-fetoprotein-low hepatocellular carcinoma
BMC Research Notes, 2010
The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. We determined the performances of α -1-acid glycoprotein (AAG) and des-γ-carboxy prothrombin (DCP) for the diagnosis of HCC, especially for α-fetoprotein (AFP)-low HCC. Methods: Of the 220 patients included in this retrospective study, 124 had HCC, and 61 (49%) of these were AFPlow HCC (AFP ≤ 20 ng/mL). The remaining 96 patients, including 49 with chronic hepatitis B or C and 47 with cirrhosis, were considered as control. Plasma AAG was analyzed using high performance liquid chromatography (HPLC) and confirmed using Western blot technique. Results: When all patients with HCC were evaluated, the area under receiver operating characteristic (ROC) curves for AAG (0.94, 95% CI: 0.91-0.97) and DCP (0.92, 95% CI: 0.88-0.95) were similar (P = 0.40). AAG had better area under ROC curve (0.96, 95% CI: 0.94-0.99) than DCP (0.87, 95% CI: 0.81-0.93) for AFP-low HCC (P < 0.05). At the specificity 95%, the sensitivity of AAG was higher in AFP-low HCC than in AFP-high HCC (82% and 62%, respectively). In contrast, higher sensitivity was obtained from DCP in discriminating HCC patients with low AFP than that in high AFP (57% and 90%, respectively). Conclusion: Our cross-sectional study showed that AAG was better performance in diagnosing HCC patients with low AFP, while DCP did better in those with high AFP.
Egyptian Liver Journal, 2013
The aim of this study was to evaluate the role of the protein induced by the absence of vitamin K or antagonist II (PIVKA-II) and the lens culinaris fraction of a-fetoprotein (AFP-L3%) in the diagnosis of patients with hepatocellular carcinoma having normal and abnormal AFP levels. Patients and methods This study was carried out on 441 individuals attending the National Liver Institute Hospital. Venous blood samples (10 ml) were drawn from all included patients and tested for liver function, viral markers (HBsAg, HCV Abs), antibilharzial antibodies, AFP, AFP-L3%, and PIVKA-II. Results Accuracy of AFP increased from 60.2 to 87.7% when levels of AFP-L3% and PIVKA-II were taken into consideration in the diagnosis of hepatocellular carcinoma (HCC) in patients with AFP levels less than 400 ng/dl, whereas it decreased from 100.0 to 82.5% when these levels were considered in the diagnosis of patients with AFP levels of 400 ng/dl or higher. Conclusion From the above findings, we conclude that in the HCC group with abnormal AFP levels (Z400 ng/ml), the serum AFP level remains the most useful tumor marker in diagnosis. The mean values of AFP-L3% appear to be more specific than mean AFP values in the diagnosis of HCC group with normal AFP levels (o400 ng/ml) as it is less often elevated in patients having cirrhosis without HCC, which does not hold true for AFP or PIVKA-II, and this implies that AFP-L3% is closely associated with the presence of HCC.
Systematic Reviews, 2013
Background: Diagnosis of early-stage hepatocellular carcinoma (HCC) followed by curative resection or liver transplantation offers the best chance for long-term patient survival. Clinically, ultrasonography has suboptimal sensitivity for detecting early-stage HCC. Several serological tests including alpha-fetoprotein (AFP), the ratio of lens culinaris agglutinin-reactive alpha-fetoprotein to total AFP (AFP-L3/AFP), des-gamma carboxyprothrombin (DCP), and glypican-3 (GPC-3) have been widely investigated as diagnostic biomarkers for early-stage HCC in at-risk populations. However, these tests are not recommended for routine HCC screening. Our objective is to determine the diagnostic performance of AFP, AFP-L3/AFP, DCP, and GPC-3 for the detection of HCC, particularly early-stage tumors meeting the Milan criteria. Methods/design: We will include cross-sectional studies that consecutively or randomly recruit target populations. We will search the Cochrane Library, Medline, Embase, Science Citation Index, and the Chinese National Knowledge Infrastructure. We will also search the MEDION and ARIF databases to identify diagnostic systematic reviews that include primary studies. Reference lists of relevant reviews will be searched for additional trials. Language restrictions will not be applied. Two reviewers will independently screen study eligibility and extract data. Methodological quality will be assessed according to the revised tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Two authors will apply the QUADAS-2 assessment to all the included studies, and any discrepancies will be resolved by the third author. The following test characteristics will be extracted into 2 × 2 tables for all included studies: true positives, false positives, true negatives, and false negatives. Study-specific estimates of sensitivity and specificity with 95% confidence intervals will be displayed in forest plots. When possible, we will use the bivariate random-effects model or the Rutter and Gatsonis hierarchical summary receiver operating characteristic model for statistical analysis. To investigate heterogeneity, we will include study designs, population characteristics, test characteristics, and types of reference standard as the study-level variables. Discussion: Our systematic review will allow patients, clinicians, and researchers to determine the diagnostic performance of AFP, AFP-L3/AFP, DCP, and GPC-3 for the detection of early-stage HCC and the potential roles of these diagnostic biomarkers in the existing diagnostic pathways.
Surgery, Gastroenterology and Oncology
Introduction: Despite its limitations, alpha-fetoprotein (AFP) is still the most common used serum marker for hepatocellular carcinoma (HCC). Alpha-fetoprotein-L3 (AFP-L3), protein induced by vitamin K absence (PIVKA-II) and Glypican-3 (GPC-3) have been proposed as complementary biomarkers but their role is still controversial. Aims and Methods: We prospectively included 101 patients with HCC and 52 control patients with liver cirrhosis with the aim to investigate the diagnostic performance of AFP, AFP-L3 PIVKA-II, and GPC-3 as single markers or in combination for HCC diagnosis. To compare the diagnostic value in distinguishing the presence of HCC from chronic nonmalignant liver disease, receiver operating characteristic (ROC) curves were constructed for each marker and for every combination of markers. Results: When all biomarkers were individually analyzed, AFP-L3 had the highest area under the curve (AUC) (0.84), followed by AFP (0.79), PIVKA-II (0.75) and GPC-3 (0.73) for HCC diagnosis. The best sensitivity (84.7%) was for AFP L3 at a cutoff >13.5ng/mL and the best specificity (93.9%) was for AFP at a cutoff >18.9 ng/mL. For combinations of two biomarkers, the AUC was highest (0.87) for AFP and AFP-L3. The combination of all four biomarkers resulted in a much better sensitivity (88.1%) and specificity (93.9%) than each of the markers individually (p = 0.01). Conclusion: AFP-L3 was the most useful single marker for HCC diagnosis, and the combination of AFP, AFP-L3 and PIVKA-II could maximize the diagnostic performance. Efforts to seek novel combination of biomarkers for HCC should be continued.