Case Control Study
Copyright ©The Author(s) 2021.
World J Gastroenterol. Dec 28, 2021; 27(48): 8343-8356
Published online Dec 28, 2021. doi: 10.3748/wjg.v27.i48.8343
Table 1 Characteristics of included patients
Global (n = 203)
Italian (n = 62) (Estimation cohort)
Spanish (n = 141) (Validation cohort)
Univariable analysis
Gender (Male)73.4% (149/203)74.2% (46/62)73.0% (103/141)0.865
mean age (yr)57.93 ± 9.7655.77 ± 10.5158.87 ± 9.22
Etiology0.001
Alcohol54.2% (110/203)41.9% (26/62)59.6% (84/141)
HCV27.1% (55/203)38.7% (24/62)22.0% (31/141)
HBV8.4% (17/203)16.1% (10/62)5% (7/144)
Others10.3% (21/203)3.2% (2/62)13.5% (19/141)
Child-Pugh0.340
A74.9% (152/203)64.5% (40/62)79.4% (112/141)
B21.2% (43/203)27.4% (17/62)18.4% (26/141)
C3.9% (8/203)8.1% (5/62)2.1% (3/141)
AST (IU/mL)51.69 ± 38.4969.17 ± 47.7444.50 ± 31.440.001
ALT (IU/mL)42.54 ± 38.6861.09 ± 56.1134.91 ± 25.160.000
Tot. Bilirubin (mg/dL)1.60 ±1.871.94 ± 2.871.45 ± 1.220.215
Creatinine (mg/dL)0.86 ± 0.680.98 ± 1.210.81 ± 0.220.292
Platelets (× 109/mL)116.00 ± 58.10100.53 ± 43.11122.45 ± 62.320.005
Albumin (mg/dL)3885.19 ± 586.663810.34 ± 613.793916.34 ± 574.960.248
AFP (ng/mL)8.09 ± 17.5012.00 ± 25.436.69 ± 12.820.101
SCCA-IgM (AU/mL)249.13 ± 332.01197.73 ± 431.13271.73 ± 276.350.144
Two-year HCC (Yes)10.8% (22/203)12.9% (8/62)9.9% (14/141)0.530
Five-year HCC (Yes)23.2% (47/203)21.0% (13/62)24.1% (34/141)0.625
Comparisons between groups were made using the Mann-Whitney U test or the Student t-test for continuous variables, and the χ2 test or the Fisher’s exact test for categorical data. P values represent the statistical significance of the differences between both subsets. Data are expressed as numbers of patients (%) or mean ± SD. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HCV: Hepatitis C virus; HBV: Hepatitis B virus; AFP: Alpha-fetoprotein; SCCA-IgM: Squamous cell carcinoma antigen and its immune complexes; Child-Pugh: The Child–Turcotte–Pugh score or Child Criteria; HCC: Hepatocellular carcinoma.
Table 2 Univariable and multivariable analysis regarding two-year hepatocellular carcinoma disease-free survival in the estimation cohort
Covariate
Non-HCC (n = 54)
HCC (n = 8)
Univariable analysis HR (95%CI; P value)
Multivariable analysis HR (95%CI; P value)
Gender (Male)75.9% (41/54)62.5% (5/8)0.571 (0.137-2.392; 0.444)
mean age (yr)55.96 ± 10.8254.5 ± 8.50.987 (0.924-1.055; 0.706)
Etiology (alcohol/HCV/HBV/other)25/17/10/21/7/0/01.075 (0.481-2.405; 0.859)
Child-Pugh (A/B/C)35/14/55/3/00.922 (0.290-2.935; 0.891)
AST (IU/mL)63.94 ± 42.21107.29 ± 69.831.013 (1.002-1.024; 0.021)
ALT (IU/mL)58.86 ± 55.4877.29 ± 62.521.004 (0.993-1.015; 0.452)
Tot. Bilirubin (mg/dL)1.97 ± 3.051.75 ± 1.020.983 (0.734-1.316; 0.906)
Creatinine (mg/dL)0.83 ± 0.202.04 ± 3.441.363 (1.055-1762; 0.018)1.564 (1.151-2.124; 0.004)
Platelets (× 109/mL)102.25 ± 43.2888.00 ± 42.890.992 (0.974-1.010; 0.387)
Albumin (mg/dL)3833 ± 6253642 ± 5251.000 (0.998-1.001; 0.394)
AFP (ng/mL)7.80 ± 9.2540.38 ± 62.711.024 (1.010-1.038; 0.001)1.028 (1.009-1.046; 0.003)
SCCA-IgM (AU/mL)136.83 ± 163.44608.75 ± 1093.531.001 (1.000-1.002; 0.004)1.001 (1.000-1.002; 0.003)
Cox proportional hazards model was used to estimate the hazard ratios and CIs in the multivariable analysis. Data are numbers of patients (%) or mean ± SD. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HCV: Hepatitis C virus; HBV: Hepatitis B virus; AFP: Alfa-fetoprotein; SCCA-IgM: Squamous cell carcinoma antigen and its immune complexes; Child-Pugh score: The Child–Turcotte–Pugh score or Child Criteria; HCC: Hepatocellular carcinoma; HR: Hazard ratio.
Table 3 Predictive discrimination ability of the combination of squamous cell carcinoma antigen immunocomplex and alfa-fetoprotein as compared with squamous cell carcinoma antigen immunocomplex or alfa-fetoprotein alone in both estimation and validation cohorts
Total patients (n = 203)
Combination of SCCA-IgM and AFP (95%CI)
SCCA-IgM (95%CI; P value)
AFP (95%CI; P value)
Estimation cohort (n = 62)
Two-year HCC-free survival0.787 (0.620-0.955)0.727 (0.526-0.927; 0.451)0.705 (0.464-0.946; 0.398)
Five-year HCC-free survival0.744 (0.613-0.876)0.686 (0.535-0.837; 0.299)0.705 (0.539-0.871; 0.581)
Validation cohort (n = 141)
Two-year HCC-free survival0.773 (0.659-0.887)0.706 (0.588-0.827; 0.122)0.748 (0.617-0.880; 0.701)
Five-year HCC-free survival0.730 (0.648-0.813)0.706 (0.623-0.788; 0.297)0.646 (0.548-0.734; 0.067)
C-index values and the corresponding 95% CIs were estimated for each main study time point to assess the model’s discrimination ability. P values represent the statistical significance of the differences between the combination and the squamous cell carcinoma antigen immunocomplex or alfa-fetoprotein alone. AFP: Alfa-fetoprotein; SCCA-IgM: Squamous cell carcinoma antigen and its immune complexes; HCC: Hepatocellular carcinoma.
Table 4 Operating characteristics for the combination of squamous cell carcinoma antigen immunocomplex and alfa-fetoprotein regarding two- and five-year hepatocellular carcinoma disease-free survival
Variables
Two-year incidence in validation cohort
Five-year incidence in validation cohort
Estimation cohort
Validation cohort
Estimation cohort
Validation cohort
Low-risk
High risk
Low-risk
High risk
Low-risk
High risk
Low-risk
High risk
Cut-offAFP < 5 ng/mL and SCCA-IgM < 124 AU/mLAFP > 5 ng/mL and SCCA-IgM > 124 AU/mLAFP < 5 ng/mL and SCCA-IgM < 124 AU/mLAFP > 5 ng/mL and SCCA-IgM > 124 AU/mLAFP < 5 ng/mL and SCCA-IgM < 124 AU/mLAFP > 5 ng/mL and SCCA-IgM > 124 AU/mLAFP < 5 ng/mL and SCCA-IgM < 124 AU/mLAFP > 5 ng/mL and SCCA-IgM > 124 AU/mL
True positive841471353312
False positive338101212878216
True negative21462610621422591
False negative040708122
Sensitivity100%50%100%50%100%38%96%35%
Specificity 39%85%20%83%43%86%23%85%
PPV20%33%12%25%32%42%29%43%
NPV100%92%100%94%100%84%96%81%
LR+1.643.381.263.021.752.691.272.36
LR-0.000.590.000.600.000.720.130.76
Correctly classified75.8%78.8%61.1%68.5%
PPV: positive predictive values; NPV: negative predictive values; LR: likelihood ratio.