Utility of Lens culinaris Agglutinin-Reactive Fraction of α-Fetoprotein and Des-Gamma-Carboxy Prothrombin, Alone or in Combination, as Biomarkers for Hepatocellular Carcinoma

Richard K. Sterling, Lennox J Jeffers, Fredric Gordon, Alan P. Venook, K. Rajender Reddy, Shinji Satomura, Futoshi Kanke, Myron E. Schwartz, Morris Sherman

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Des-gamma-carboxy prothrombin (DCP) and Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) are surveillance markers used to detect hepatocellular carcinoma (HCC) in Japan. This study evaluated their utility, alone or in combination, in a North American population. Methods: Patients with hepatitis C virus-related cirrhosis were followed up prospectively for 2 years. Results: Of 372 patients, HCC developed in 34 of 298 who were free of HCC at entry. The overall sensitivity, specificity, and positive and negative predictive values for only AFP (>20 ng/mL) were 61%, 71%, 34%, and 88%, respectively; for only AFP-L3% (>10) were 37%, 92%, 52%, and 85%, respectively; and for only DCP (>7.5 ng/mL) were 39%, 90%, 48%, and 86%, respectively. Values increased when AFP values were combined with AFP-L3% and DCP to 77%, 59%, 32%, and 91%, respectively. Among patients with increases in AFP levels to 20 to 200 ng/mL, AFP-L3% and DCP were highly specific markers (86.6% and 90.2%, respectively). Of 29 HCC patients with AFP levels less than 20 ng/mL, 13 had increased levels of AFP-L3% or DCP. Increased alanine aminotransferase levels were associated with increased total AFP but not AFP-L3% or DCP levels. Both AFP-L3%- and DCP-positive patients showed significant differences in lower cumulative HCC-free rates compared with the overall group (P < .0001 and P = .0005, respectively). Conclusions: AFP-L3% and DCP levels have higher correlation values with an absence of HCC, as well as a higher specificity and negative predictive value, than total AFP. Although this combination of markers only marginally improves surveillance for early HCC, it could identify individuals with negative imaging results who would benefit from follow-up evaluation.

Original languageEnglish
Pages (from-to)104-113
Number of pages10
JournalClinical Gastroenterology and Hepatology
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2009

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Fetal Proteins
Hepatocellular Carcinoma
Biomarkers
lentil lectin
acarboxyprothrombin
Alanine Transaminase
Hepacivirus
Japan
Fibrosis
Sensitivity and Specificity

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Utility of Lens culinaris Agglutinin-Reactive Fraction of α-Fetoprotein and Des-Gamma-Carboxy Prothrombin, Alone or in Combination, as Biomarkers for Hepatocellular Carcinoma. / Sterling, Richard K.; Jeffers, Lennox J; Gordon, Fredric; Venook, Alan P.; Reddy, K. Rajender; Satomura, Shinji; Kanke, Futoshi; Schwartz, Myron E.; Sherman, Morris.

In: Clinical Gastroenterology and Hepatology, Vol. 7, No. 1, 01.01.2009, p. 104-113.

Research output: Contribution to journalArticle

Sterling, Richard K. ; Jeffers, Lennox J ; Gordon, Fredric ; Venook, Alan P. ; Reddy, K. Rajender ; Satomura, Shinji ; Kanke, Futoshi ; Schwartz, Myron E. ; Sherman, Morris. / Utility of Lens culinaris Agglutinin-Reactive Fraction of α-Fetoprotein and Des-Gamma-Carboxy Prothrombin, Alone or in Combination, as Biomarkers for Hepatocellular Carcinoma. In: Clinical Gastroenterology and Hepatology. 2009 ; Vol. 7, No. 1. pp. 104-113.
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abstract = "Background & Aims: Des-gamma-carboxy prothrombin (DCP) and Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) are surveillance markers used to detect hepatocellular carcinoma (HCC) in Japan. This study evaluated their utility, alone or in combination, in a North American population. Methods: Patients with hepatitis C virus-related cirrhosis were followed up prospectively for 2 years. Results: Of 372 patients, HCC developed in 34 of 298 who were free of HCC at entry. The overall sensitivity, specificity, and positive and negative predictive values for only AFP (>20 ng/mL) were 61{\%}, 71{\%}, 34{\%}, and 88{\%}, respectively; for only AFP-L3{\%} (>10) were 37{\%}, 92{\%}, 52{\%}, and 85{\%}, respectively; and for only DCP (>7.5 ng/mL) were 39{\%}, 90{\%}, 48{\%}, and 86{\%}, respectively. Values increased when AFP values were combined with AFP-L3{\%} and DCP to 77{\%}, 59{\%}, 32{\%}, and 91{\%}, respectively. Among patients with increases in AFP levels to 20 to 200 ng/mL, AFP-L3{\%} and DCP were highly specific markers (86.6{\%} and 90.2{\%}, respectively). Of 29 HCC patients with AFP levels less than 20 ng/mL, 13 had increased levels of AFP-L3{\%} or DCP. Increased alanine aminotransferase levels were associated with increased total AFP but not AFP-L3{\%} or DCP levels. Both AFP-L3{\%}- and DCP-positive patients showed significant differences in lower cumulative HCC-free rates compared with the overall group (P < .0001 and P = .0005, respectively). Conclusions: AFP-L3{\%} and DCP levels have higher correlation values with an absence of HCC, as well as a higher specificity and negative predictive value, than total AFP. Although this combination of markers only marginally improves surveillance for early HCC, it could identify individuals with negative imaging results who would benefit from follow-up evaluation.",
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T1 - Utility of Lens culinaris Agglutinin-Reactive Fraction of α-Fetoprotein and Des-Gamma-Carboxy Prothrombin, Alone or in Combination, as Biomarkers for Hepatocellular Carcinoma

AU - Sterling, Richard K.

AU - Jeffers, Lennox J

AU - Gordon, Fredric

AU - Venook, Alan P.

AU - Reddy, K. Rajender

AU - Satomura, Shinji

AU - Kanke, Futoshi

AU - Schwartz, Myron E.

AU - Sherman, Morris

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N2 - Background & Aims: Des-gamma-carboxy prothrombin (DCP) and Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) are surveillance markers used to detect hepatocellular carcinoma (HCC) in Japan. This study evaluated their utility, alone or in combination, in a North American population. Methods: Patients with hepatitis C virus-related cirrhosis were followed up prospectively for 2 years. Results: Of 372 patients, HCC developed in 34 of 298 who were free of HCC at entry. The overall sensitivity, specificity, and positive and negative predictive values for only AFP (>20 ng/mL) were 61%, 71%, 34%, and 88%, respectively; for only AFP-L3% (>10) were 37%, 92%, 52%, and 85%, respectively; and for only DCP (>7.5 ng/mL) were 39%, 90%, 48%, and 86%, respectively. Values increased when AFP values were combined with AFP-L3% and DCP to 77%, 59%, 32%, and 91%, respectively. Among patients with increases in AFP levels to 20 to 200 ng/mL, AFP-L3% and DCP were highly specific markers (86.6% and 90.2%, respectively). Of 29 HCC patients with AFP levels less than 20 ng/mL, 13 had increased levels of AFP-L3% or DCP. Increased alanine aminotransferase levels were associated with increased total AFP but not AFP-L3% or DCP levels. Both AFP-L3%- and DCP-positive patients showed significant differences in lower cumulative HCC-free rates compared with the overall group (P < .0001 and P = .0005, respectively). Conclusions: AFP-L3% and DCP levels have higher correlation values with an absence of HCC, as well as a higher specificity and negative predictive value, than total AFP. Although this combination of markers only marginally improves surveillance for early HCC, it could identify individuals with negative imaging results who would benefit from follow-up evaluation.

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