Study population
A total of 108 patients were included in the current study (80 males, 28 females; median age, 69 [21–87] years). The METAVIR fibrosis stage according to FibroScan was F1, F2, F3, and F4 in 2, 36, 39, and 17 of the 94 patients, respectively. The median (range) FIB-4 index in HCC patients was 4.27 (0.3–13.7), and the median (range) M2BPGi level was 2.79 (0.29–8.75) (Table 1). SVR was seen in 30 out of the 108 patients, and failure to achieve sustained virological response (non-SVR) was observed in 64 patients. SVR status was determined by blood test before surgery. Details on non-SVR and SVR are shown in Table 2.
Box plots of FibroScan, VTQ, FIB-4 index and M2BPGi
All patients
The box plots of the METAVIR scores with respect to each method are shown in Figure 1. According to Spearman's rank correlation analysis, positive correlations between each method and the METAVIR fibrosis stage were observed (FibroScan: r=0.61, p≤0.001; VTQ: r=0.64, p≤0.001; FIB-4 index: r=0.40, p≤0.001; and M2BPGi: r=0.32, p=0.01). The median values for each method were as follows: FibroScan, F0-1: 5.3, F2: 8.8, F3: 13.1, F4: 22.8; VTQ, F0-1: 1.17, F2: 1.38, F3: 1.88, F4: 2.42; FIB-4 index, F0-1: 1.41, F2: 2.78, F3: 4.20, F4: 4.04; M2BPGi, F0-1: 1.29, F2: 1.71, F3: 2.37, F4: 3.60 (Figure 1). The r values for FibroScan and VTQ were higher than those for FIB-4 index and M2BPGi.
Non-SVR group
The results for the non-SVR group are shown in Figure 2. The fibrosis stages of 14 control patients were defined as F0-1 in the analysis. According to Spearman's rank correlation analysis, positive correlations between each method and the METAVIR fibrosis stage were observed (FibroScan: r=0.65, p≤0.001; VTQ: r=0.70, p≤0.001; FIB-4 index: r=0.44, p≤0.001; and M2BPGi: r=0.31, p=0.01). The median values for each method were as follows: FibroScan, F0-1: 5.1, F2: 8.9, F3: 13.6, F4: 22.0; VTQ, F0-1: 1.14, F2: 1.40, F3: 1.89, F4: 2.39; FIB-4 index, F0-1: 1.52, F2: 4.18, F3: 4.88, F4: 6.05; M2BPGi, F0-1: 0.62, F2: 1.90, F3: 2.37, F4: 3.53 (Figure 2). The r values for FibroScan and VTQ were higher than those for FIB-4 index and M2BPGi.
SVR group
The results for the SVR group are shown in Figure 3. The fibrosis stages of the 14 control patients were defined as F0-1 in the analysis. According to Spearman's rank correlation analysis, positive correlations between each method and the METAVIR fibrosis stage were observed (FibroScan: r=0.58, p≤0.001; VTQ: r=0.65, p≤0.001; FIB-4 index: r=0.59, p≤0.001; and M2BPGi: r=0.54, p≤0.001). The median values for each method were as follows: FibroScan, F0-1: 5.1, F2: 8.4, F3: 13.1, F4: 24.6; VTQ, F0-1: 1.14, F2:1.27, F3: 1.82, F4: 3.10; FIB-4 index, F0-1: 1.31, F2: 2.00, F3: 3.94, F4: 3.31; M2BPGi, F0-1: 0.62, F2: 0.96, F3: 2.64, F4: 3.45 (Figure 3). The r values for VTQ were higher than those of FibroScan, FIB-4 index and M2BPGi.
ROC analysis of FibroScan, VTQ, FIB-4 index and M2BPGi
All patients
The sensitivity, specificity, and cut-off values were compared among the four diagnostic methods. The ROC curves for each method are shown in Figure 4 (Figure 4). The areas under the ROC curve (AUC) for diagnosis of fibrosis stage F2 or greater were as follows: 0.95 for FibroScan, 0.93 for VTQ, 0.87 for the FIB-4 index, and 0.81 for the M2BPGi level. The respective values for diagnosis of grade F3 or greater were 0.85, 0.83, 0.67, and 0.67, and those for diagnosis of F4 were 0.89, 0.86, 0.65, and 0.76 (Figure 4). In the ROC comparison, there was a significant difference in "VTQ vs FIB-4 index", "FibroScan vs FIB-4 index", "FibroScan vs M2BPGi" , "VTQ vs M2BPGi"in the F0-2 vs F3-4 group, "VTQ vs FIB-4 index", "FibroScan vs FIB-4 index", "FibroScan vs M2BPGi" in the F0-3 vs F4 group (Figure 4). The cutoff values for each test for a diagnosis of grade F2 or greater were as follows: FibroScan, 5.6; VTQ, 1.26; FIB-4 index, 1.74; M2BPGi, 1.63. The respective values for a diagnosis of F3 or greater were 9.8, 1.78, 3.20, and 2.15, and those for a diagnosis of F4 were 16.0, 1.94, 4.56, and 2.70 (Table 3).
Non-SVR group
The results for the non-SVR group are shown in Figure 5 (Figure 5). The fibrosis stage of the 14 control patients were defined as F0-1 in the analysis. The AUC for diagnosis of fibrosis stage F2 or greater were as follows: 0.94 for FibroScan, 0.89 for VTQ, 0.85 for the FIB-4 index, and 0.77 for the M2BPGi level. The respective values for a diagnosis of grade F3 or greater were 0.85, 0.84, 0.74, and 0.73, and those for a diagnosis of F4 were 0.91, 0.88, 0.67, and 0.78. In the ROC comparison, there were significant differences in "VTQ vs FIB-4 index", "FibroScan vs FIB-4 index", "FibroScan vs M2BPGi" in the F0-2 vs F3-4 group, "VTQ vs FIB-4 index", "FibroScan vs FIB-4 index", "FibroScan vs M2BPGi", "VTQ vs M2BPGi" in the F0-3 vs F4 group. The cutoff values for each test for a diagnosis of grade F2 or greater were as follows: FibroScan, 6.2; VTQ, 1.27; FIB-4 index, 1.74; M2BPGi, 1.40. The respective values for a diagnosis of F3 or greater were 8.9, 1.46, 2.91, and 1.76, and those for a diagnosis of F4 were 15.0, 1.94, 3.25, and 2.70. (Table4)
SVR group
The results for the SVR group are shown in Figure 5S (Figure 5S). The fibrosis stages of the 14 control patients were defined as F0-1 in the analysis. The AUC for a diagnosis of fibrosis stage F2 or greater were as follows: 0.98 for FibroScan, 0.78 for VTQ, 0.78 for the FIB-4 index, and 0.63 for the M2BPGi level. The respective values for a diagnosis of grade F3 or greater were 0.91, 0.89, 0.89, and 0.77, and those for a diagnosis of F4 were 0.94, 0.94, 0.77, and 0.77 (Figure 5S). In the ROC comparison, there were significant differences in "FibroScan vs VTQ", "FibroScan vs FIB-4 index", "FibroScan vs M2BPGi" in the F0-1 vs F2-4 group, "FibroScan vs FIB-4 index" in the F0-3 vs F4 group. The cutoff values for each test for a diagnosis of grade F2 or greater were as follows: FibroScan, 6.2; VTQ, 1.27; FIB-4 index, 1.90; M2BPGi, 1.00. The respective values for a diagnosis of F3 or greater were 9.6, 1.56, 2.70, and 1.50, and those for a diagnosis of F4 were 21.5, 2.63, 2.82, and 2.56. (Table4S)