Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients.
As data on the effectiveness of tumor markers in detecting hepatocellular carcinoma (HCC) in cirrhotic patients are limited, we investigated the diagnostic accuracy of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3).



This retrospective study enrolled 361 cirrhotic patients with HCC, and 276 cirrhotic patients without HCC occurrence.



Most patients were men (n = 431, 67.7%); the median age was 57.0 years. The main etiology of chronic liver disease was chronic hepatitis B (n = 467, 73.3%). The sensitivity and specificity of combined three biomarkers was 87.0 and 60.1% in overall HCC, and 75.7 and 60.1% in early HCC, respectively (cutoff: 20 ng/mL for AFP, 40 mAU/mL for PIVKA-II, and 5% for AFP-L3). The area under the receiver operating characteristic curve (AUROC) for HCC diagnosis was 0.765 (95% confidence interval [CI], 0.728-0.801) for AFP; 0.823 (95% CI, 0.791-0.854) for PIVKA-II; and 0.755 (95% CI, 0.718-0.792) for AFP-L3. The AUROC for early HCC diagnosis was 0.754 (95% CI, 0.691-0.816) for AFP, 0.701 (95% CI, 0.630-0.771) for PIVKA-II, and 0.670 (95% CI, 0.596-0.744) for AFP-L3. Combining the three tumor markers increased the AUROC to 0.877 (95% CI, 0.851-0.903) for HCC diagnosis, and 0.773 (95% CI, 0.704-0.841) for early HCC diagnosis.



Diagnostic accuracy improved upon combining the AFP, PIVKA-II, and AFP-L3 tumor markers compared to each marker alone in detecting HCC and early HCC in cirrhotic patients.
a Department of Internal Medicine and.
Tae Seop
TS
Lim
a Department of Internal Medicine and.
Do Young
DY
Kim
a Department of Internal Medicine and.
Kwang-Hyub
KH
Han
b Department of Laboratory Medicine , Yonsei University College of Medicine , Seoul , Republic of Korea.
Hyon-Suk
HS
Kim
a Department of Internal Medicine and.
Seung Hwan
SH
Shin
a Department of Internal Medicine and.
Kyu Sik
KS
Jung
a Department of Internal Medicine and.
Beom Kyung
BK
Kim
a Department of Internal Medicine and.
Seung Up
SU
Kim
a Department of Internal Medicine and.
Jun Yong
JY
Park
a Department of Internal Medicine and.
Sang Hoon
SH
Ahn
D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis* / Q000821:virology; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000821:virology; D008297:Male; D008875:Middle Aged; D037121:Plant Lectins / Q000276:immunology; D020033:Protein Isoforms / Q000097:blood; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D012372:ROC Curve; D012189:Retrospective Studies; D000509:alpha-Fetoproteins / Q000276:immunology / Q000378:metabolism
D015415:Biomarkers; D014408:Biomarkers, Tumor; D037121:Plant Lectins; D020033:Protein Isoforms; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C033619:lentil lectin; C008208:acarboxyprothrombin; D011516:Prothrombin
AFP; AFP-L3; PIVKA-II; biomarker; hepatocellular carcinoma