Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma.
OBJECTIVE
Alpha-fetoprotein (AFP) is widely used as a surveillance test for hepatocellular carcinoma (HCC) among patients with cirrhosis. Des-gamma carboxy-prothrombin (DCP) and lectin-bound AFP (AFP-L3%) are potential surveillance tests for HCC. The aims of this study were to determine performance of DCP and AFP-L3% for the diagnosis of early HCC; whether they complement AFP; and what factors affect DCP, AFP-L3%, or AFP levels.


METHODS
We conducted a large phase 2 biomarker case-control study in 7 academic medical centers in the United States. Controls were patients with compensated cirrhosis and cases were patients with HCC. AFP, DCP, and AFP-L3% levels were measured blinded to clinical data in a central reference laboratory.


RESULTS
A total of 836 patients were enrolled: 417 (50%) were cirrhosis controls and 419 (50%) were HCC cases, of which 208 (49.6%) had early stage HCC (n = 77 very early, n = 131 early). AFP had the best area under the receiver operating characteristic curve (0.80, 95% confidence interval [CI]: 0.77-0.84), followed by DCP (0.72, 95% CI: 0.68-0.77) and AFP-L3% (0.66, 95% CI: 0.62-0.70) for early stage HCC. The optimal AFP cutoff value was 10.9 ng/mL leading to a sensitivity of 66%. When only those with very early HCC were evaluated, the area under the receiver operating characteristic curve for AFP was 0.78 (95% CI: 0.72-0.85) leading to a sensitivity of 65% at the same cutoff.


CONCLUSIONS
AFP was more sensitive than DCP and AFP-L3% for the diagnosis of early and very early stage HCC at a new cutoff of 10.9 ng/mL.
University of Michigan, Ann Arbor, Michigan 48109, USA. jmarrero@umich.edu
Jorge A
JA
Marrero
Ziding
Z
Feng
Yinghui
Y
Wang
Mindie H
MH
Nguyen
Alex S
AS
Befeler
Lewis R
LR
Roberts
K Rajender
KR
Reddy
Denise
D
Harnois
Josep M
JM
Llovet
Daniel
D
Normolle
Jackie
J
Dalhgren
David
D
Chia
Anna S
AS
Lok
Paul D
PD
Wagner
Sudhir
S
Srivastava
Myron
M
Schwartz
D000046:Academic Medical Centers; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000209:etiology / Q000473:pathology; D016022:Case-Control Studies; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D037102:Lectins / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood*; D011516:Prothrombin; D012372:ROC Curve; D012680:Sensitivity and Specificity; D014481:United States; D000509:alpha-Fetoproteins / Q000032:analysis*
C097353:AFP protein, human; D015415:Biomarkers; D014408:Biomarkers, Tumor; D037102:Lectins; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin