Dataset Information

Improved Detection of Hepatocellular Carcinoma by Using a Longitudinal Alpha-Fetoprotein Screening Algorithm.

ABSTRACT: Hepatocellular carcinoma (HCC) has limited treatment options when diagnosed at advanced stages; therefore, early detection is critical to reduce mortality. There is disagreement about the value of ?-fetoprotein (AFP) in HCC surveillance. We aim to improve the sensitivity of AFP in HCC surveillance by using an algorithm that incorporates screening history to define patient-specific thresholds for positive a screen.De-identified data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial, which enrolled 1050 patients with hepatitis C and advanced fibrosis or cirrhosis who were prospectively followed every 3-6 months, were analyzed. AFP was assayed at each visit, and ultrasonography was performed every 6-12 months. A panel adjudicated the diagnosis of HCC. A parametric empirical Bayes (PEB) screening algorithm, which incorporates screening history, was compared with a single threshold approach for interpreting AFP results.During a median follow-up of 80 months, 88 patients (48 of 427 with cirrhosis and 40 of 621 with advanced fibrosis) were diagnosed with HCC. PEB improved the sensitivity of AFP for detecting all HCC from 60.4% to 77.1% (P < .0005) in patients with cirrhosis and from 72.5% to 87.5% (P = .0015) in patients with advanced fibrosis, when the false-positive rate among all screenings was set at 10%. PEB algorithm detected HCC 1.7-1.9 years earlier in the cirrhosis group and 1.4-1.7 years earlier in the advanced fibrosis group, compared with single threshold approach.PEB increases the sensitivity of AFP testing and detects HCC earlier among hepatitis C patients with advanced fibrosis or cirrhosis. These data should prompt a reevaluation of how AFP is used in combination with ultrasound in HCC surveillance.

SUBMITTER: Tayob N

PROVIDER: S-EPMC4744807 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Improved Detection of Hepatocellular Carcinoma by Using a Longitudinal Alpha-Fetoprotein Screening Algorithm.

Tayob Nabihah N Lok Anna S F AS Do Kim-Anh KA Feng Ziding Z

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20150807 3

<h4>Background & aims</h4>Hepatocellular carcinoma (HCC) has limited treatment options when diagnosed at advanced stages; therefore, early detection is critical to reduce mortality. There is disagreement about the value of α-fetoprotein (AFP) in HCC surveillance. We aim to improve the sensitivity of AFP in HCC surveillance by using an algorithm that incorporates screening history to define patient-specific thresholds for positive a screen.<h4>Methods</h4>De-identified data from the Hepatitis C A ...[more]

PMID: 26260109

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Project description:INTRODUCTION:serum alpha-fetoprotein (AFP) was routinely employed as a tumor marker for screening, diagnosis, and treatment follow-up of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients had normal AFP level even at an advanced disease status. Few studies to date had tried to explore the nature and behavior of this normal AFP HCC (N-HCC). The purpose of this study was to investigate the clinicopathological characteristics and survival outcome of N-HCC after operation. In addition, potential tumor markers for N-HCC were also sought in an attempt to augment diagnostic ability. METHODS:between 2005 and 2015, patients with hepatocellular carcinoma who were treated with hepatectomy in Chang Gung Memorial Hospital Linkou branch were divided into two groups according to their preoperative serum AFP level (<15 ng/mL: NHCC; ?15 ng/mL: abnormal AFP HCC (A-HCC)). Patient demographic data and clinicopathological variables were collected. Kaplan-Meier and Cox regression multivariate analyses were performed to identify significant risk factors for disease-free survival (DFS) and overall survival (OS) for N-HCC. ELISA and immunohistochemical (IHC) studies were employed to determine the diagnostic accuracy of various tumor markers. RESULTS:a total of 1616 patients (78% male) who underwent liver resection for HCC were included in this study. Of them, 761 patients (47.1%) were N-HCC. N-HCC patients were significantly older with more comorbidities and less hepatitis virus infections. Furthermore, N-HCC had fewer early recurrences (49.6% vs. 60.8%, p < 0.001) and better DFS (44.6 months vs. 23.6 months, p < 0.001) and OS (94.5 months vs. 81.7 months, p < 0.001). Both ELISA and IHC studies demonstrated that glypican-3 (GPC3) would be a promising diagnostic tumor marker for N-HCC. CONCLUSION:N-HCC patients were significantly older and had less hepatitis virus infections or cirrhosis. Their tumors tended to be smaller, less vascular invaded, and well-differentiated. The carcinogenesis of N-HCC may thus not be identical to that of typical HCC. GPC3 would be a promising tumor marker for diagnosing N-HCC. Further study is warranted to validate our findings.

Project description:Background & aimsUltrasound (US)-based screening has been recommended for patients with an increased risk of hepatocellular carcinoma (HCC). US analysis, however, is limited in patients who are obese or have small tumors. The addition of serum level of α-fetoprotein (AFP) measurements to US analysis can increase detection of HCC. We analyzed data from patients with chronic liver disease, collected over 15 years in an HCC surveillance program, to develop a model to assess risk of HCC.MethodsWe collected data from 3450 patients with chronic liver disease undergoing US surveillance in Japan from March 1998 through April 2014, and followed them up for a median of 8.83 years. We performed longitudinal discriminant analysis of serial AFP measurements (median number of observations/patient, 56; approximately every 3 months) to develop a model to determine the risk of HCC. We validated the model using data from 2 cohorts of patients with chronic liver disease in Japan (404 and 2754 patients) and 1 cohort in Scotland (1596 patients).ResultsHCC was detected in 413 patients (median tumor diameter, 1.8 cm), during a median follow-up time of 6.60 years. In the development data set, the model identified patients who developed HCC with an area under the curve of 0.78; it correctly identified 74.3% of patients who did develop HCC, and 72.9% of patients who did not. Overall, 73.1% of patients were classified correctly. The model could be used to assign patients to a high-risk group (27.5 HCCs/1000 patient-years) vs a low-risk group (4.9 HCCs/1000 patient-years). A similar performance was observed when the model was used to assess patients with cirrhosis. Analysis of the validation cohorts produced similar results.ConclusionsWe developed and validated a model to identify patients with chronic liver disease who are at risk for HCC based on change in serum AFP level over time. The model could be used to assign patients to high-risk vs low-risk groups, and might be used to select patients for surveillance.

Dataset Information

Improved Detection of Hepatocellular Carcinoma by Using a Longitudinal Alpha-Fetoprotein Screening Algorithm.

Publications

Improved Detection of Hepatocellular Carcinoma by Using a Longitudinal Alpha-Fetoprotein Screening Algorithm.

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