Improved Performance of Serum Alpha-Fetoprotein for Hepatocellular Carcinoma Diagnosis in HCV Cirrhosis with Normal Alanine Transaminase
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. Data from the NCI Early Detection Research Network phase II HCC bioma...
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| Published in: | Cancer epidemiology, biomarkers & prevention Vol. 26; no. 7; pp. 1085 - 1092 |
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| Main Authors: | , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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01.07.2017
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| ISSN: | 1538-7755 |
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| Abstract | 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.
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.
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 serum ALT ≤40 U/L than patients with serum ALT >40 U/L (0.91 vs. 0.75,
< 0.01). At 90% specificity, the sensitivity of AFP increased from 44% to 74% in Whites with HCV and from 50% to 85% in non-Whites with HCV. There was a trend toward higher AUC in HCV patients with serum ALT ≤40 U/L than those with serum ALT >40 U/L (0.79 vs. 0.69,
= 0.10) in the validation cohort.
The satisfactory performance of AFP in HCV patients with normal ALT should be further validated.
The AFP may serve as a valuable surveillance test in HCV patients with normal ALT.
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| AbstractList | 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.
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.
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 serum ALT ≤40 U/L than patients with serum ALT >40 U/L (0.91 vs. 0.75,
< 0.01). At 90% specificity, the sensitivity of AFP increased from 44% to 74% in Whites with HCV and from 50% to 85% in non-Whites with HCV. There was a trend toward higher AUC in HCV patients with serum ALT ≤40 U/L than those with serum ALT >40 U/L (0.79 vs. 0.69,
= 0.10) in the validation cohort.
The satisfactory performance of AFP in HCV patients with normal ALT should be further validated.
The AFP may serve as a valuable surveillance test in HCV patients with normal ALT.
. 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 serum ALT ≤40 U/L than patients with serum ALT >40 U/L (0.91 vs. 0.75, P < 0.01). At 90% specificity, the sensitivity of AFP increased from 44% to 74% in Whites with HCV and from 50% to 85% in non-Whites with HCV. There was a trend toward higher AUC in HCV patients with serum ALT ≤40 U/L than those with serum ALT >40 U/L (0.79 vs. 0.69, P = 0.10) in the validation cohort.Conclusions: The satisfactory performance of AFP in HCV patients with normal ALT should be further validated.Impact: The AFP may serve as a valuable surveillance test in HCV patients with normal ALT. Cancer Epidemiol Biomarkers Prev; 26(7); 1085-92. ©2017 AACR. |
| Author | Yamada, Hiroyuki Singal, Amit G Gores, Gregory J Harnois, Denise M Yang, Ju Dong Nguyen, Mindie H Befeler, Alex S Dai, Jianliang Reddy, K Rajender Feng, Ziding Marrero, Jorge A Gopal, Purva Addissie, Benyam D Schwartz, Myron Roberts, Lewis R |
| Author_xml | – sequence: 1 givenname: Ju Dong surname: Yang fullname: Yang, Ju Dong organization: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota – sequence: 2 givenname: Jianliang surname: Dai fullname: Dai, Jianliang organization: Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas – sequence: 3 givenname: Amit G surname: Singal fullname: Singal, Amit G organization: Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas – sequence: 4 givenname: Purva surname: Gopal fullname: Gopal, Purva organization: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas – sequence: 5 givenname: Benyam D surname: Addissie fullname: Addissie, Benyam D organization: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota – sequence: 6 givenname: Mindie H surname: Nguyen fullname: Nguyen, Mindie H organization: Division of Gastroenterology, Stanford University Medical Center, Palo Alto, California – sequence: 7 givenname: Alex S surname: Befeler fullname: Befeler, Alex S organization: Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, Missouri – sequence: 8 givenname: K Rajender surname: Reddy fullname: Reddy, K Rajender organization: Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania – sequence: 9 givenname: Myron surname: Schwartz fullname: Schwartz, Myron organization: Department of General Surgery, The Mount Sinai Medical Center, New York, New York – sequence: 10 givenname: Denise M surname: Harnois fullname: Harnois, Denise M organization: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Jacksonville, Florida – sequence: 11 givenname: Hiroyuki surname: Yamada fullname: Yamada, Hiroyuki organization: Wako Diagnostics, Mountain View, California – sequence: 12 givenname: Gregory J surname: Gores fullname: Gores, Gregory J organization: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota – sequence: 13 givenname: Ziding surname: Feng fullname: Feng, Ziding organization: Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas – sequence: 14 givenname: Jorge A surname: Marrero fullname: Marrero, Jorge A organization: Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas – sequence: 15 givenname: Lewis R surname: Roberts fullname: Roberts, Lewis R email: roberts.lewis@mayo.edu organization: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. roberts.lewis@mayo.edu |
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| Snippet | The utility of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is controversial. We aimed to identify factors associated with elevated... Background: The utility of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is controversial. We aimed to identify factors associated... |
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| SubjectTerms | Adult Aged Alanine Transaminase - blood Alcoholism - complications alpha-Fetoproteins - analysis Carcinoma, Hepatocellular - blood Carcinoma, Hepatocellular - diagnosis Carcinoma, Hepatocellular - pathology Early Detection of Cancer - methods Female Hepacivirus - isolation & purification Hepatitis B virus - isolation & purification Humans Liver Cirrhosis - blood Liver Cirrhosis - etiology Liver Neoplasms - blood Liver Neoplasms - diagnosis Liver Neoplasms - pathology Male Middle Aged Neoplasm Staging ROC Curve |
| Title | Improved Performance of Serum Alpha-Fetoprotein for Hepatocellular Carcinoma Diagnosis in HCV Cirrhosis with Normal Alanine Transaminase |
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