Des-gamma-carboxyprothrombin, alpha-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma.
OBJECTIVE
Hepatocellular carcinoma (HCC) is a common complication in patients with chronic viral hepatitis. Detection of HCC at an early stage is critical for a favorable clinical outcome. The study aim was to: (i) compare the levels of des-gamma-carboxyprothrombin (DCP), alpha-fetoprotein (AFP) and AFP-L3 in HCC patients and in chronic viral hepatitis patients without HCC; (ii) define the level of each tumor marker with the best sensitivity and specificity for HCC diagnosis; and (iii) to correlate the levels of these markers with respect to size and tumor burden.


METHODS
Two hundred and forty patients with either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection were studied. These included 144 with HCC, 47 with chronic hepatitis (fibrosis stage I-III on liver biopsy) and 49 with cirrhosis.


RESULTS
Levels of DCP, AFP and AFP L-3 were significantly higher in patients with HCC than in those without HCC (P < or = 0.0001). Receiver-operating curves (ROC) indicated that the cut-off value with the best sensitivity and specificity for each test was > or =84 mAU/mL for DCP, > or =25 ng/mL for AFP and > or =10% for AFP-L3. The sensitivity, specificity and positive predictive value (PPV) for DCP was 87%, 85% and 86.8%, for AFP 69%, 87% and 69.8%, and for AFP-L3 56%, 90% and 56.1%, respectively. DCP levels were below the ROC cut-off in all patients without HCC. In patients with single lesions, there was a direct correlation of DCP to tumor size. High levels of AFP correlated with diffuse type of HCC. All three markers were significantly elevated in the presence of metastatic HCC. No advantage was observed by combining two or three markers for HCC diagnosis.


CONCLUSIONS
DCP had the highest sensitivity and PPV for HCC diagnosis, had a direct correlation with tumor size, and was not elevated in any patients without HCC. DCP should be used as the main serum test for HCC detection.
Durazo
Francisco A
FA
The Pfleger Liver Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. fdurazo@mednet.ucla.edu
Blatt
Lawrence M
LM
Corey
William G
WG
Lin
Jiing-Huey
JH
Han
Steven
S
Saab
Sammy
S
Busuttil
Ronald W
RW
Tong
Myron J
MJ
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology / Q000821:virology; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood / Q000150:complications* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood*; D011516:Prothrombin; D012372:ROC Curve; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000032:analysis*
C097353:AFP protein, human; D015415:Biomarkers; D014408:Biomarkers, Tumor; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin