Improved performance of serum alpha-fetoprotein for hepatocellular carcinoma diagnosis in hcv cirrhosis with normal alanine transaminase

Ju Dong Yang, Jianliang Dai, Amit G. Singal, Purva Gopal, Benyam D. Addissie, Mindie H. Nguyen, Alex S. Befeler, K. Rajender Reddy, Myron Schwartz, Denise Harnois, Hiroyuki Yamada, Gregory James Gores, Ziding Feng, Jorge A. Marrero, Lewis Rowland Roberts

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1085-1092
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume26
Issue number7
DOIs
StatePublished - Jul 1 2017

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alpha-Fetoproteins
Alanine Transaminase
Hepatocellular Carcinoma
Fibrosis
Hepacivirus
Serum
ROC Curve
Area Under Curve
Alcohols
Biomarkers
Sensitivity and Specificity

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Improved performance of serum alpha-fetoprotein for hepatocellular carcinoma diagnosis in hcv cirrhosis with normal alanine transaminase. / Yang, Ju Dong; Dai, Jianliang; Singal, Amit G.; Gopal, Purva; Addissie, Benyam D.; Nguyen, Mindie H.; Befeler, Alex S.; Reddy, K. Rajender; Schwartz, Myron; Harnois, Denise; Yamada, Hiroyuki; Gores, Gregory James; Feng, Ziding; Marrero, Jorge A.; Roberts, Lewis Rowland.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 26, No. 7, 01.07.2017, p. 1085-1092.

Research output: Contribution to journalArticle

Yang, JD, Dai, J, Singal, AG, Gopal, P, Addissie, BD, Nguyen, MH, Befeler, AS, Reddy, KR, Schwartz, M, Harnois, D, Yamada, H, Gores, GJ, Feng, Z, Marrero, JA & Roberts, LR 2017, 'Improved performance of serum alpha-fetoprotein for hepatocellular carcinoma diagnosis in hcv cirrhosis with normal alanine transaminase', Cancer Epidemiology Biomarkers and Prevention, vol. 26, no. 7, pp. 1085-1092. https://doi.org/10.1158/1055-9965.EPI-16-0747
Yang, Ju Dong ; Dai, Jianliang ; Singal, Amit G. ; Gopal, Purva ; Addissie, Benyam D. ; Nguyen, Mindie H. ; Befeler, Alex S. ; Reddy, K. Rajender ; Schwartz, Myron ; Harnois, Denise ; Yamada, Hiroyuki ; Gores, Gregory James ; Feng, Ziding ; Marrero, Jorge A. ; Roberts, Lewis Rowland. / Improved performance of serum alpha-fetoprotein for hepatocellular carcinoma diagnosis in hcv cirrhosis with normal alanine transaminase. In: Cancer Epidemiology Biomarkers and Prevention. 2017 ; Vol. 26, No. 7. pp. 1085-1092.
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title = "Improved performance of serum alpha-fetoprotein for hepatocellular carcinoma diagnosis in hcv cirrhosis with normal alanine transaminase",
abstract = "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.",
author = "Yang, {Ju Dong} and Jianliang Dai and Singal, {Amit G.} and Purva Gopal and Addissie, {Benyam D.} and Nguyen, {Mindie H.} and Befeler, {Alex S.} and Reddy, {K. Rajender} and Myron Schwartz and Denise Harnois and Hiroyuki Yamada and Gores, {Gregory James} and Ziding Feng and Marrero, {Jorge A.} and Roberts, {Lewis Rowland}",
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T1 - Improved performance of serum alpha-fetoprotein for hepatocellular carcinoma diagnosis in hcv cirrhosis with normal alanine transaminase

AU - Yang, Ju Dong

AU - Dai, Jianliang

AU - Singal, Amit G.

AU - Gopal, Purva

AU - Addissie, Benyam D.

AU - Nguyen, Mindie H.

AU - Befeler, Alex S.

AU - Reddy, K. Rajender

AU - Schwartz, Myron

AU - Harnois, Denise

AU - Yamada, Hiroyuki

AU - Gores, Gregory James

AU - Feng, Ziding

AU - Marrero, Jorge A.

AU - Roberts, Lewis Rowland

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

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