Development And Validation Of A Simple Model For Detection Of Early Hepatocellular Carcinoma In A Liver Cirrhosis Cohort

Abstract

Aim: We aimed to develop a simple model combining protein induced by vitamin K antagonist-II (PIVKA-II) and alpha-fetoprotein (AFP) to detect early hepatocellular carcinoma (HCC) in liver cirrhosis (LC) patients.

Method: One hundred and sixty-nine newly diagnosed early HCC patients and 242 LC patients without HCC were enrolled in the current case-control study. All subjects were randomly divided into analysis group and validation group. Serum levels of PIVKA-II, AFP and other laboratory parameters were detected. Chi-squared test, t-test and logistic regression were employed in statistical analysis.

Results: PIVKA-II level in early HCC was significantly higher than that in LC (90.97 mAU/mL vs 18.00 mAU/mL, P < 0.01), as well as AFP level (15.00 ng/mL vs 2.00 ng/mL, P < 0.01) in analysis groups. Multivariate analysis showed that PIVAK-II, AFP, gender, and age were independent risk factors for early HCC detection among LC patients. A logistic regression model and a simple model combining PIVKA and AFP were conducted to detect early HCC. The ROC curve showed that among analysis groups, the area under the ROC curve (AUROC) of the logistic regression model and the simple model were 0.96 (95% CI 0.94-0.98) and 0.94 (95% CI 0.92-0.97), respectively. At a cut-off value of 56.03 the sensitivity and specificity of the simple model were 81.1% and 91.4%, respectively. In the validation group, the sensitivity and specificity of the simple model was 82.4% and 94.2%, respectively. The two models are comparable statistically for early HCC detection, but the logistic regression requires complex calculation.

Conclusion: The present study indicates that the simple model combining PIVKA-II and AFP has comparable diagnostic efficiency in contrast to the logistic model but is easy to use clinically. It might be helpful for early HCC detection among liver cirrhosis patients.

Keywords: AFP; PIVKA-II; hepatocellular carcinoma; liver cirrhosis.

Figure 1

Difference of PIVKA and AFP plasma levels after logarithmic transformation between early HCC patients and liver cirrhosis in the analysis group. (A) Serum level of PIVKA-II among early HCC patients was 90.97 (9.7–30,766.38) mAU/mL, significantly higher than that of LC patients at 18 (3.49–626.34) mAU/mL (P < 0.01) in analysis group. (B) Serum level of AFP among early HCC patients was 15 (0.9–19,549.1) ng/mL, significantly higher than that of LC patients at 2.00 (0.6–121.8) ng/mL (P < 0.01) in analysis group.

Figure 2

Diagnostic values of AFP (green), PIVKA-II (purple), the logistic regression model (blue), and the simple model (red) for early HCC detection among lLC patients in the analysis group.

Figure 3

Diagnostic values of the logistic regression model and the simple model for early HCC detection among LC patients in the validation group.

Figure 4

Validity of the predictive performance of the logistic model (A) and the simple model (B) in estimating the probabilities of early HCC in the validation group (n= 177).