A scoring model combining serum alpha-fetoprotein and tumor size and number predicts prognosis in hepatitis B virus-related hepatocellular carcinoma patients after curative hepatectomy

Abstract

Background: More in-depth models, such as biomarker and anatomical information, are needed to predict individualized prognoses of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative liver resection. alpha-fetoprotein (AFP) has conflicting value in predicting prognosis. We aimed to investigate the significance of an AFP score model as a potential predictor of prognosis after radical resection in patients with HBV-related HCC.

Methods: This study retrospectively analyzed 397 patients with HBV-related HCC who underwent hepatic resection between 2001 and 2013. Serum AFP level, tumor size, and tumor number were calculated by adding individual points for the AFP score model. Patient and tumor characteristics were tested for prognostic significance using ANOVA and chi-squared test, respectively. The receiver operating characteristic (ROC) curve was used to identify the AFP score model with or without other risk factors to discriminate patients. Kaplan-Meier and Cox's analyses were performed to pinpoint risk factors for overall survival (OS) and disease-free survival (DFS) in the patients.

Results: The cutoff value for the AFP score model was set at 2 using the ROC curve, with good specificity and sensitivity for OS and DFS. According to the AFP score model, 185 patients were in the AFP score >2 group, and 212 were in the AFP score ≤2 group. The median OS in the AFP score ≤2 and AFP score >2 groups were 173.4±1.00 vs. 50.30±8.67 m, respectively (P=0.000). The median DFS in the AFP score ≤2 and AFP score >2 groups were 17.20±3.66 vs. 73.7±10.39 m (P=0.000), respectively. Analyses from Cox's multivariate proportional hazard model indicated that AFP score (HR =0.563, 95% CI: 0.398-0.798, P=0.001), MVI (HR =0.653, 95% CI: 0.441-0.967, P=0.033), and cirrhosis (HR =0.358, 95% CI: 0.185-0.696, P=0.002) were risk factors for OS. The multivariate Cox model identified MVI (HR =1.589, 95% CI: 1.496-2.854, P=0.003) and AFP score (HR =0.876, 95% CI: 0.404-0.925, P=0.040) as risk factors of DFS. According to the stratification by the AFP score with MVI, the mean OS in the AFP score >2 group combined with the MVI group was significantly shorter, compared with that in the AFP score >2 group without the MVI group (65.58±9.18 vs. 94.21±8.25 m, P=0.024). The mean OS in the AFP score >2 group combined with the cirrhosis group is significantly shorter than that in the AFP score ≤2 group without the cirrhosis group (64.08±7.38 vs. 145.31±8.38 m, P=0.000).

Conclusions: The AFP score model categorizes HCC patients with relatively good liver function after radical resection with low- and high-risk prognosis.

Keywords: AFP score model; Hepatocellular carcinoma (HCC); prognosis.

Figure 1

Chart flow. HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HBV, hepatitis B virus; AFP, alpha-fetoprotein.

Figure 2

The receivers operating characteristics (ROC) curve showing the overall accuracy of the AFP score and AFP >400 µg/L risk factors for predicting prognoses. The optimal cut-off point of the AFP score is 2. AFP, alpha-fetoprotein.

Figure 3

The Kaplan-Meier analysis of OS and DFS in 397 patients subdivided according to their AFP score. The cut-off point of 2 (green line denoted an AFP score >2; blue line denotes an AFP score ≤2). OS, overall survival; DFS, disease-free survival; AFP, alpha-fetoprotein; m, months.

Figure 4

The Kaplan-Meier analysis and ROC curve in 397 patients stratified by the AFP score combined with MVI or cirrhosis (P1, P2, and P3 indicate the data compared to AFP score ≤2 without MVI or cirrhosis). In Figure 4A, 66 patients with an AFP score >2 with MVI, 103 patients with an AFP score >2 without MVI, 23 patients with an AFP score ≤2 with MVI, and 205 patients with an AFP score ≤2 without MVI had their OS compared using the Kaplan-Meier analysis (blue line denotes an AFP score ≤2 without MVI; green line denoted an AFP score ≤2 with MVI; yellow line denotes an AFP score >2 without MVI; red line denotes an AFP score >2 with MVI). Similarly, in Figure 4C, 90 patients with an AFP score >2 with cirrhosis, 80 patients with an AFP score >2 without cirrhosis, 145 patients with an AFP score ≤2 with cirrhosis, and 82 patients with an AFP score ≤2 without cirrhosis had their OS compared using the Kaplan-Meier analysis (blue line denotes an AFP score ≤2 without MVI; green line denotes an AFP score ≤2 with MVI; yellow line denotes an AFP score >2 without MVI; red line denotes an AFP score >2 with MVI). In Figures 4B and D, the ROC curve analysis shows the accuracy of the AFP score combined with MVI or cirrhosis in discriminating between subgroups. ROC, receiver operating characteristic; MVI, microvascular invasion; AFP, alpha-fetoprotein; m, months.