[Surveillance of cirrhosis for hepatocellular carcinoma--clinical validation of new serological biomarkers for improved diagnosis].
Alpha-Fetoprotein (AFP) is a serological marker currently available for the detection of hepatocellular carcinoma (CHC). Its poor sensitivity renders it unsatisfactory for this purpose and suggests the need for additional biomarkers. Squamous cell carcinoma associated antigen (SCCA) is physiologically present in the skin and was recently detected in patients with CHC. Additionally, circulating immunoglobulin M complexes associated with SCCA (CICSCC) and AFP (CICAFP) have been identified in the blood of these patients.


METHODS
The accuracy of the new biomarkers in detecting CHC was evaluated in 72 patients using an ELISA test. Sensitivity and specificity were determined for each marker alone and all markers combined for their ability to detect CHC and discriminate between CHC and hepatic cirrhosis (CH).


RESULTS
The median AFP was 402.000 ng/mL (IQR 23.267-1210.000) in CHC and 4.950 ng/mL (IQR 3.213-11.678) in CH patients (p <0.0001). The median CICAFP was 68.276 AU/mL (IQR 14.913-150.000) in CHC and 16.910 (IQR 9.439-40.846) AU/mL in CH patients (p = 0.0171). The median SCCA was 0.587 IU/mL (IQR 0.354-1.349) in HCC and 0.427 IU/mL (IQR 0.178-0.531) in CH patients (p = 0.0191). The median CICSCC was 18,753 AU/mL at HCC (IQR 14.820-40.813) and 14.433 AU/mL (IQR 13.077-17.643) in HC patients (p = 0.0153). The AFP efficacy, as measured by the area under the curve (AUC), was 0.878 (95% CI= 0.780-0.943). For a cut-off value (diagnostic threshold) of 18.44 ng/mL, the sensitivity and specificity were 80% and 92.6%, respectively, and the positive predictive value (PPV) and a negative predictive value (NPV) were 94.7 and 73.5, respectively. For SCCA, AUC was 0.666 (95% CI 0.545-0.773) and the cut-off value was 0.533 IU/mL. The sensitivity and specificity were 55.6% 77.8%, respectively, and the PPV and NPV were 80.6 and 51.2, respectively. For AFP-CIC, AUC was 0.705 (95% CI 0.559-0.825) and the cut-off value was 73.51 AU/mL. Sensitivity and specificity were 50% and 88.9%, respectively, and PPV and NPV were 88.9 and 50, respectively. For SCC-CIC, AUC was 0708 (95% CI 0.563-0.828) and the cut-off value was 17.643 AU/mL. Sensitivity and specificity were 59.4% and 77.8%, respectively, and PPV and NPV were 82.6 and 51.9, respectively.


CONCLUSIONS
This study suggests that using a combination of AFP, SCCA, CICSCC, and CICAFP in clinical practice may provide a new test which could increase accuracy ofCHC noninvasive diagnosis.
Universitatea de Medicină şi Farmacie Gr. T. Popa Iaşi Facultatea de Medicină, Institutul de Gastroenterologie şi Hepatologie Iaşi.
Irina
I
Teofănescu
Elena
E
Gologan
Gabriela
G
Stefănescu
Gh
G
Bălan
D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D015843:Serpins / Q000097:blood; D000509:alpha-Fetoproteins / Q000378:metabolism
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015843:Serpins; D000509:alpha-Fetoproteins; C051072:squamous cell carcinoma-related antigen