Alpha Fetoprotein; Useful as Screening Test for Hepatocellular Carcinoma Due to Chronic Hepatitis C (original) (raw)
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Annals of Hepatology, 2015
The objective of this study was to establish modified cutoff values of serum alpha-fetoprotein (AFP) according to hepatitis status. While AFP is used as a serum marker in the diagnosis or monitoring of hepatocellular carcinoma (HCC), its use as a screening method to the general population is controversial. We evaluated its screening performance in a hepatitis prevalent East Asian population, and suggest different cutoff values according to the individual's hepatitis status. We evaluated the performance of AFP as a screening test in 48,123 consecutive Koreans during the period from March, 2012 to August, 2013 who underwent routine health checks at a single institution. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated with fixed cutoff and with modified cutoffs according the individual's hepatitis status. A total of 24 out of 48,123 subject (0.05%) were newly diagnosed with HCC after screening. Among the 1,874 subject with positive hepatitis B virus surface antigen (HBsAg), 17 (0.91%) developed HCC, compared with two out of 393 (0.51%) individuals with hepatitis C virus antibody (anti-HCV). Five out of 45,855 (0.01%) subject with neither HBsAg nor anti-HCV developed HCC. Compared to the performance of a fixed cutoff, specificity, PPV, and NPV improved without sacrificing sensitivity when applying modified cutoff. In conclusion, our findings suggest that AFP with modified cutoffs according to the individual's hepatitis status might be a useful screening marker for HCC in hepatitis prevalent areas.
Background: The use of alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) surveillance has been debatable. A decrease in AFP was demonstrated in cirrhotic hepatitis C patients with sustained virological response (SVR) to direct-acting antivirals (DAAs). Aim of the study: Evaluation of the role of AFP as a surveillance test for HCC in hepatitis C cirrhotic patients who achieved SVR to DAAs. Patients and Methods: A cohort of 258 cirrhotic patients with hepatitis C virus (HCV) underwent HCC surveillance by AFP and ultrasound every 6 months and followed-up for >1 year with at least 3 AFP measurements. Another 102 patients with HCV-related HCC were included and AFP was estimated at diagnosis. Both SVR-12 and viremic patients were included. Results: AFP in SVR cirrhotic patients was significantly lower than viremic patients (median 6 vs. 9 ng/ml respectively) (P= 0.002). 67.4% and 12.3% of SVR cirrhotic patients had AFP ≤10, ≥20 ng/ml vs. 35% and 25.8 % of viremic patients respectively (P<0.001). There were no significant differences in AFP level or the proportion of AFP estimation levels between SVR and viremic HCC patients (P>0.05). AFP cutoff for HCC diagnosis was 10 ng/ml in SVR patients (sensitivity 70.4%; specificity 90%; PPV 65.6%; NPV 91.8% and accuracy 82.2%) and 15 ng/ml in viremic patients (sensitivity 66.7%; specificity 79.3%; PPV 57.1%, NPV 85.2% and accuracy 71.7%). Conclusion: AFP is more effective as a surveillance test for the early detection of HCC in HCV cirrhotic patients with SVR to DAAs. The decline in AFP values after SVR optimizes its diagnostic accuracy.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2017
Background: The utility of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is controversial. We aimed to identify factors associated with elevated AFP and define the patients for whom AFP is effective for surveillance.Methods: Data from the NCI Early Detection Research Network phase II HCC biomarker study (233 early-stage HCC and 412 cirrhotic patients) were analyzed. We analyzed 110 early-stage HCC and 362 cirrhotic hepatitis C virus (HCV) patients for external validation. Sensitivity, specificity, and area under the ROC curve (AUC) for HCC were calculated.Results: HCV etiology, non-White race, and serum alanine transaminase (ALT) predicted elevated AFP in cirrhotics. Non-White race and ALT predicted elevated AFP in HCC patients. Higher AUC of AFP for HCC was noted in patients with HBV (0.85) and alcohol (0.84), whereas it was lower in patients with hepatitis C virus (HCV; 0.80) and nonviral/alcohol etiology (0.76). The AUC was higher in HCV patients with se...
Journal of Medical Microbiology & Diagnosis, 2014
Background and aims: Early detection of Hepatocellular Carcinoma (HCC) is crucial for effective management. Incidence of HCC has increased in the United States largely attributed to hepatitis B and C virus. Lens culinaris agglutinin-reactive Alpha-Fetoprotein (AFP-L3) and Des-Gamma-Carboxy Prothrombin (DCP) are being recognized specific biomarkers for HCC. Methods: We measured AFP-L3 and DCP in serial serum specimens of a cohort of chronic hepatitis patients on HCC surveillance and compared these markers to abdominal imaging. Among fifty patients who developed HCC during surveillance, 30 were included in the study with available sera 1-2 years before, at diagnosis and post ablation of HCC. For controls, three consecutive annual sera were examined from 106 chronic hepatitis patients without HCC during surveillance for 5-10 years. The µTASWako i30 auto analyzer was used for the assay that utilizes the microfluidics chip based assay platform. It can fractionate AFP-L3 glycoform and calculates AFP-L3% if AFP level is ≥ 0.6 ng/mL. Results: Combination of AFP, AFP-L3 and DCP showed high sensitivity of 83% in all patients and 75% in patients with AFP<20 ng/mL. AFP-L3 and DCP assays were useful in patients with low levels of AFP (<20 ng/mL) and could detect significant AFP-L3% elevation in some patients more than one year before the diagnosis of HCC. Furthermore, AFP-L3 predicted recurrence of HCC. Conclusions: This is the first study in the U.S. patients using the µTASWako i30 analyzer to test these HCC biomarkers. Our results suggest that combinations of these biomarkers are highly useful for early detection of HCC.
J Viral Hepatitis, 2007
The clinical significance of elevated serum alphafetoprotein (AFP) in patients with chronic hepatitis C virus (HCV) infection is not well defined. We analysed data from a population-based cohort of patients with HCV infection to assess the prevalence of elevated serum AFP, to determine its association with clinical and virologic parameters and with clinical outcomes. We defined a slightly elevated serum AFP level as 8 to <15 and a high-AFP level as ‡15 lg ⁄ L. Among 541 HCV-RNA-positive persons, 61 (11%) had a slightly elevated or high AFP at the time of consent. AFP ‡8 lg ⁄ L was associated with the older age, aspartate aminotransferase ⁄ alanine aminotransferase ratio >1, and higher alkaline phosphatase levels, but not with heavy alcohol use, IV drug use, genotype, viral load or duration of HCV infection. Among 192 persons with an AFP at liver biopsy, 17% had an AFP ‡8 lg ⁄ L. The sensitivity ⁄ specificity of an AFP level ‡8 in detecting Ishak 3-6 fibrosis was 39% ⁄ 95%. Among 372 persons with a minimum of four AFP measurements over 6 years, 5% had persistently elevated AFP >8 lg ⁄ L, 19% had both elevated and normal AFP measurements, and 76% had persistently normal AFP. Elevated AFP at consent was associated with hepatocellular carcinoma (HCC) and end-stage liver disease. Over 6 years of follow-up, persistently elevated AFP was associated with the development of HCC; no person with AFP persistently <8 lg ⁄ mL developed HCC. Serial AFP measurements appear to be useful in identifying persons with advanced fibrosis and help to determine who needs periodic screening with liver ultrasound to detect HCC.
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.
PLOS ONE, 2016
Detection of hepatocellular carcinoma (HCC) through screening can improve outcomes. However, HCC surveillance remains costly, cumbersome and suboptimal. We tested whether and how serum Alpha-Fetoprotein (AFP) should be used in HCC surveillance. Record linkage, dedicated pathways for management and AFP data-storage identified i) consecutive highly characterised cases of HCC diagnosed in 2009-14 and ii) a cohort of ongoing HCC-free patients undergoing regular HCC surveillance from 2009. These two well-defined Scottish patient cohorts enabled us to test the utility of AFP surveillance. Of 304 cases of HCC diagnosed over 6 years, 42% (129) were identified by a dedicated HCC surveillance programme. Of these 129, 47% (61) had a detectable lesion first identified by screening ultrasound (US) but 38% (49) were prompted by elevated AFP. Despite pre-HCC diagnosis AFP >20kU/L being associated with poor outcome, 'AFP-detected' tumours were offered potentially curative management as frequently as 'US-detected' HCCs; and had comparable survival. Linearity of serial log 10-transformed AFPs in HCC cases and in the screening 'HCC-free' cohort (n = 1509) provided indicators of high-risk AFP behaviour in HCC cases. An algorithm was devised in static mode, then tested dynamically. A case/control series in hepatitis C related disease demonstrated highly significant detection (p<1.72*10 −5) of patients at high risk of developing HCC. These data support the use of AFP in HCC surveillance. We show proof-of-principle that an automated and further refineable algorithmic interpretation of AFP can identify patients at higher risk of HCC. This approach could provide a cost-effective, user-friendly and much needed addition to US surveillance.
Evaluation of HCV-associated Hepatocellular Carcinoma based on Alpha-fetoprotein levels
Afro-Egyptian Journal of Infectious and Endemic Diseases, 2019
Background and study aim: Alphafetoprotein (AFP) cannot be relied on alone for diagnosis of hepatocellular carcinoma (HCC). However, it may have a prognostic value and can be used for monitoring response to different modalities of treatment for HCC. This study aimed to differentiate the clinical and pathological features of HCCs according to AFP levels. Subjects and Methods: This retrospective study included 60 patients with HCC secondary to chronic hepatitis C (HCV). They were divided based on serum AFP into two groups; group I; included 30 patients with AFP lower than 302.5ng/ml. and group II; included 30 patients with AFP higher than 302.5ng/ml. clinical, laboratory and pathological differences between both groups were compared. Results: Regarding the pathological features, patients with higher AFP secreting tumors have larger tumor size compared to lower AFP secreting tumors; (5.8 cm Vs. 4.5 cm, P value; 0.001). Number of lesions and tumor location were similar between the two groups. Conclusion: HCC-secreting high levels of AFP are larger and aggressive tumors when compared to low secreting AFP-HCC.