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Supplementary files for:

Validation of the GALAD Model and Establishment of GAAP Model for Diagnosis of Hepatocellular Carcinoma in Chinese patients

Miaoxia Liu1,2$, Ruihong Wu1,3$, Xu Liu1, Hongqin Xu1, Xiumei Chi1,3, Xiaomei Wang1, Mengru Zhan1, Bao Wang1, Fei Peng1, Xiuzhu Gao1,3, Ying Shi1, Xiaoyu Wen1, Yali Ji3, Qinglong Jin1, Junqi Niu1

1Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin, China; 2Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; 3Phase I Clinical Research Center, First Hospital of Jilin University, Changchun, Jilin, China;

$These authors contributed equally to this work

Correspondence: Qinglong Jin Department of Hepatology, First Hospital of Jilin University, 71 Xin Min Street, Changchun 130021, China Tel +86-431-81875103 Fax +86-431-81875103 Email [email protected]

Supplementary Figure S1. Correlation of serum AFP and PIVKA-II. Spearman correlation analysis was used for correlation analysis. n=625, horizontal line represented the cut-off value of PIVKA-II at 28.23 mAU/mL, vertical line represented the cut-off value of AFP at 12.62 ng/mL.

Supplementary Figure S2. Serum ALT in CHB, HCC, HBV related Cirrhosis and CHC.

HCC consisted of HBV related HCC and HCV related HCC. Kruskal-wallis H test was used for comparison among three groups, and post hoc Dunn's Multiple Comparison test was performed for pairwise comparison.*** P<0.001,* P<0.05, ns P＞0.05.

Supplementary Figure S3. Correlation between ALT and AFP (A), and PIVKA-II (B). Spearman correlation analysis was used for correlation analysis.

Supplementary Figure S4. Serum AFP and PIVKA-II in HCC with or without Cirrhosis and different Child-Pugh score. (A) AFP level in HCC with Cirrhosis vs without Cirrhosis. (B) PIVKA-II level in HCC with Cirrhosis vs without Cirrhosis. (C) AFP level in HCC with different Child-Pugh score. (D) PIVKA-II level in HCC with different Child-Pugh score. Mann-whitney U test was used for Comparison between two groups, Kruskal-wallis H was used for Comparison among three groups.

Supplementary Figure S5. Performances of GALAD, GALAD-C, GAAP, individual biomarkers in differentiating of HCC and CLD patients with negative AFP (<20ng/mL). The entire dataset, all HCC and CLD patients in table 1 with negative AFP (A); HCV subset, HCC and CLD with HCV infection and negative AFP (B); HBV subset, HCC and CLD with HBV infection and negative AFP (C). Sen, sensitivity; Spe, specificity; Ppv, positive predictive value; Npv, negative predictive value; Ccp, percent correctly classified. *Four kinds of cutoff points were defined. The first one was the cutoff point maximizing sensitivity while keeping specificity at 80% based on the corresponding subset locally. The second one was the cutoff point maximizing sensitivity while keeping specificity at 90% based on the corresponding subset locally. The third one was the cutoff point maximizing the sum of the sensitivity and specificity based on the corresponding subset locally. The fourth one was the cutoff point maximizing the sum of the sensitivity and specificity based on all the HCC and CLD patients in the table 1 with negative AFP.

Supplementary Figure S6. Performances of GALAD, GALAD-C, GAAP, individual biomarkers in differentiating of HCC and Other malignant liver tumor (A), HCC vs. ICC patients (B), HCC vs. liver metastases (C), and HCC vs. healthy controls (D). Sen, sensitivity; Spe, specificity; PPV, positive predictive value; NPV, negative predictive value.

Supplementary Figure S7. Correlation between AFP (A), PIVKA-II (B), GALAD-C (C) and GAAP (D) with maximum tumor diameter.

Supplementary Figure S8. AFP (A), PIVKA-II (B), GALAD-C score (C) and GAAP score (D) in patients with or without portal vein invasion. PVI, Portal Vein Invasion; HCC without PVI (n=193), HCC with PVI (n=41).

Supplementary Figure S9. Conjugated Bilirubin (CB) in ICC, HCC, Cirrhosis, Chronic Hepatitis, MT and HC. ICC, intrahepatic cholangiocarcinoma; HCC, hepatocellular carcinoma (HCC); MT, liver metastases; HC, healthy Controls. Mann-whitney U test was used for Comparison between two groups. *** P<0.001, ** P<0.01, * P<0.05.

Supplementary Table S1. Comparison of serum AFP, PIVKA-II in HBV related liver disease and HCV related liver disease

Variable

HBV related HCC

N=135

HCV related HCC

N=106

HBV related Cirrhosis

N=102

HCV related Cirrhosis

N=84

CHB

N=47

CHC

N=49

H

P value

AFP

(ng/mL)

25.28

(5.55-543.8)

36.68

(9.22-371.9)

3.62

(2.26-10.99)

5.01

(3.06-17.34)

12.0

(4.47-145.4)

4.20

(2.71-9.85)

113.5

＜0.001

PIVKA-II

(mAU/mL)

124.3

(30.0-793.5)

396.7

(45.0-2391)

18.2

(14.1-27.8)

20.0

(14.2-27.9)

24.2

(19.1-32.9)

22.66

(18.0-31.6)

222.1

＜0.001

Note: Kruskal-wallis H was used for Comparison between 6 groups. HBV, Hepatitis B Virus; HCV, Hepatitis C Virus; CHB, Chronic Hepatitis B; CHC, Chronic Hepatitis C.

Supplementary Table S2. Parameter estimates (SE) and OR (95% CI) of variables by logistic regression in GALAD-C and GAAP models

Variable

β (SE)

OR (95% CI)

P

GALAD-C score (based on all HCC patients and all CLD patients in Table 1)

= -11.501 + 0.733 [Gender (1 for male, 0 for female)] + 0.099 [Age] + 0.073 [AFP-L3%] + 0.840 log10 [AFP] + 2.364 log10 [PIVKA-II]

Constant

-11.501 (1.171)

-

-

Gender (Male vs Female)

0.733 (0.295)

2.082 (1.167-3.714)

0.013

Age (years)

0.099 (0.015)

1.104 (1.072-1.136)

＜0.001

AFP-L3%

0.073 (0.020)

1.075 (1.033-1.119)

＜0.001

Log10(AFP)

0.840 (0.183)

2.317(1.618-3.319)

＜0.001

Log10(PIVKA-II)

2.346 (0.318)

10.636 (5.707-19.822)

＜0.001

GAAP score (based on all HCC patients and all CLD patients in Table 1)

= -11.203 + 0.699 [Gender (1 for male, 0 for female)] + 0.094 [Age] + 1.076 log10 [AFP] + 2.376 log10 [PIVKA-II]

Constant

-11.203 (1.111)

-

-

Gender (Male vs Female)

0.699 (0.284)

2.012 (1.152-3.512)

0.014

Age (years)

0.094 (0.014)

1.099 (1.069-1.130)

＜0.001

Log10 (AFP)

1.076 (0.176）

2.932 (2.078-4.138)

＜0.001

Log10 (PIVKA-II)

2.376 (0.308）

10.765 (5.882-19.703)

＜0.001

Supplementary Table S3. ROC curve analysis of GALAD, GALAD-C, GAAP and individual serum biomarkers for discriminating HCC (n=242) and cirrhosis (n=187)

Model/biomarker

cut-off value

AUC（95%CI）

P value (GALAD-C vs others)

Sensitivity %

Specificity%

PPV %

NPV %

Correctly classified %

GALAD

0.946

0.893(0.864-0.922)

0.0192

81.8

79.7

83.9

77.2

80.9

GALAD-C

-0.374

0.916(0.891-0.942)

/

82.6

85.0

87.7

79.1

83.7

GAAP

-0.650

0.907(0.879-0.934)

0.0430

87.2

77.0

83.1

82.3

82.8

PIVKA-II mAU/mL

28.23

0.876(0.844-0.908)

0.0033

82.6

75.9

81.6

77.2

79.7

AFP ng/ml

12.62

0.773(0.730-0.817)

<0.0001

64.5

74.9

76.8

61.9

69

AFP-L3%

1.744

0.719(0.671-0.767)

<0.0001

54.1

86.6

84.0

59.3

68.3

Note: AUC=area under receiver operating characteristic curve; PPV= Positive Predictive Value; NPV= Negative Predictive Value.

Supplementary Table S4. ROC curve analysis of GALAD, GALAD-C, GAAP and individual serum biomarkers for discriminating HCC (n=242) and Hepatitis (n=96)

Model/biomarker

cut-off value

AUC（95%CI）


Sensitivity %

Specificity%

PPV %

NPV %


GALAD

0.946

0.887(0.848-0.927)

<0.0001

81.8

80.2

91.2

63.6

81.4

GALAD-C

-0.374

0.934(0.908-0.96)

/

82.6

87.5

94.3

66.7

84.0

GAAP

-0.650

0.927(0.898-0.956)

0.1786

87.2

83.3

93.0

72.1

86.1

PIVKA-II mAU/mL

28.23

0.856(0.817-0.896)

<0.0001

82.6

70.8

87.7

61.8

79.3

AFP ng/ml

12.62

0.706(0.646-0.765)

<0.0001

64.5

66.7

83.0

42.7

65.1

AFP-L3%

1.744

0.696(0.641-0.752)

<0.0001

54.1

80.2

87.3

41.0

61.5


Supplementary Table S5. ROC curve analysis of GALAD, GALAD-C, GAAP and individual serum biomarkers for discriminating HCC within Milan criteria (n=86) and CLD (n=283)

Model/biomarker

cut-off value

AUC（95%CI）


Sensitivity %

Specificity%

PPV %

NPV %


GALAD

0.946

0.810(0.761-0.859)

0.0984

62.8

79.9

48.6

87.6

75.9

GALAD-C

-0.374

0.841(0.794-0.889)

/

61.6

85.9

57.0

88.0

80.2

GAAP

-0.650

0.840(0.793-0.887)

0.8121

70.9

79.2

50.8

90.0

77.2

PIVKA-II mAU/mL

28.23

0.801(0.748-0.854)

0.0983

72.1

74.2

45.9

89.7

73.7

AFP ng/ml

12.62

0.679(0.615-0.742)

<0.0001

51.2

72.1

35.8

82.9

67.2

AFP-L3%

1.744

0.602(0.529-0.675)

<0.0001

34.9

84.5

40.5

81.0

72.9


Supplementary Table S6. ROC curve analysis of GALAD, GALAD-C, GAAP and individual serum biomarkers for discriminating HCC with maximum diameter ＜ 5cm (n=145) and CLD (n=283)

Model/biomarker

cut-off value

AUC（95%CI）


Sensitivity %

Specificity%

PPV %

NPV %


GALAD

0.946

0.855(0.819-0.892)

0.0102

74.5

79.9

65.5

85.9

78.0

GALAD-C

-0.374

0.889(0.856-0.921)

/

73.8

85.9

72.8

86.5

81.8

GAAP

-0.650

0.882(0.849-0.915)

0.1433

80.7

79.2

66.5

88.9

79.7

PIVKA-II mAU/mL

28.23

0.827(0.787-0.868)

0.0008

76.6

74.2

60.3

86.1

75.0

AFP ng/ml

12.62

0.730(0.681-0.780)

<0.0001

60.7

72.1

52.7

78.2

68.2

AFP-L3%

1.744

0.669(0.610-0.727)

<0.0001

46.9

84.5

60.7

75.6

71.7


Supplementary Table S7. ROC curve analysis of GALAD, GALAD-C, GAAP and individual serum biomarkers for discriminating HCC with maximum diameter ≥ 5cm (n=75) and CLD (n=283)

Model/biomarker

cut-off value

AUC（95%CI）


Sensitivity %

Specificity%

PPV %

NPV %


GALAD

0.946

0.960(0.937-0.982)

0.0029

94.7

79.9

55.5

98.3

83.0

GALAD -C

-0.374

0.983(0.969-0.998)

/

96.0

85.9

64.3

98.8

88.0

GAAP

-0.650

0.982(0.966-0.997)

0.1298

98.7

79.2

55.6

99.6

83.2

PIVKA-II mAU/mL

28.23

0.969(0.946-0.993)

0.0121

97.3

74.2

50.0

99.1

79.1

AFP ng/ml

12.62

0.793(0.729-0.856)

<0.0001

70.7

72.1

40.2

90.3

71.8

AFP-L3%

1.744

0.782(0.710-0.853)

<0.0001

65.3

84.5

52.7

90.2

80.4


Supplementary Table S8. ROC curve analysis of serum biomarkers alone, GALAD-C and GAAP for discriminating HCC and CLD stratified by etiology.

Model/biomarker

cut-off value

AUC（95%CI）


Sensitivity %

Specificity%

PPV%

NPV %


With HCV etiology, HCC ( n=106 ) vs CLD ( cirrhosis =84, hepatitis = 49 )

GALAD

0.946

0.939(0.911-0.966)

0.024

89.6

81.2

79.2

90.8

84.9

GALAD-C

-0.374

0.958(0.936-0.981)

/

92.5

83.5

81.7

93.3

87.4

GAAP

-0.650

0.954(0.931-0.977)

0.145

95.3

72.9

73.7

95.1

82.8

PIVKA-II mAU/mL

28.23

0.909(0.872-0.947)

0.002

87.7

75.2

73.8

88.5

80.8

AFP ng/ml

12.62

0.797(0.739-0.854)

<0.001

68.9

73.7

67.6

74.8

71.5

AFP-L3%

1.744

0.777(0.714-0.841)

<0.001

60.4

89.5

82.1

73.9

76.6

AFP+PIVKA-II

Same as above

0.72(0.655-0.785)

<0.001

90.6

53.4

60.8

87.7

69.9

AFP+AFP-L3%

Same as above

0.718(0.652-0.785)

<0.001

70.8

72.9

67.6

75.8

72

AFP+PIVKA-II+AFP-L3%

Same as above

0.716(0.651-0.781)

<0.001

90.6

52.6

60.4

87.5

69.5

With HBV etiology, HCC ( n=135 ) vs CLD ( cirrhosis = 102, hepatitis = 47)

GALAD

0.946

0.855(0.812-0.897)

<0.001

75.6

78.5

76.1

78.0

77.1

GALAD-C

-0.374

0.904(0.869-0.939)

/

75.6

87.9

85.0

79.9

82

GAAP

-0.650

0.894(0.857-0.931)

0.179

80.7

84.6

82.6

82.9

82.7

PIVKA-II mAU/mL

28.23

0.839(0.793-0.884)

<0.001

78.5

73.8

73.1

79.1

76.1

AFP ng/ml

12.62

0.719(0.661-0.778)

<0.001

60.7

70.5

65.1

66.5

65.8

AFP-L3%

1.744

0.658(0.593-0.722)

<0.001

49.6

79.9

69.1

63.6

65.5

AFP+PIVKA-II

Same as above

0.72(0.66-0.78)

<0.001

90.4

53.7

63.9

86.0

71.1

AFP+AFP-L3%

Same as above

0.679(0.616-0.742)

<0.001

65.9

69.8

66.4

69.3

68

AFP+PIVKA-II+AFP-L3%

Same as above

0.728(0.669-0.787)

<0.001

92.6

53.0

64.1

88.8

71.8


Supplementary Table S9. Diagnostic efficiency of GAAP in test dataset

Model for Validate Data N=308

AUC (95%CI)

cut-off value

Sensitivity %

Specificity %

FPR

%

FNR

%

Correctly

classified

%

GAAP

0.922(0.893-0.950)

-0.650

88(149/169)

80(111/139)

12(20/169)

20(28/139)

84(260/308)

AUC=area under receiver operating characteristic curve; FPR, false positive rate; FNR, false negative rate.

Supplementary Table S10. Distributions of tumor size in HCC patients with different etiologies

tumor size

all (n=242)

HCV (n=106)

HBV (n=135)

unifocal < 2cm

29 (12.0)

6 (5.7)

23 (17.0)

unifocal < 3cm

55 (22.7)

14 (13.2)

40 (29.6)

unifocal < 4cm

71 (29.3)

21 (19.8)

49 (36.3)

unifocal < 5cm

81 (33.5)

26 (24.5)

54 (40.0)

unifocal < 10cm

97 (40.1)

32 (30.2)

64 (47.4)

Within Milan criteria

86 (35.5)

29 (27.4)

56 (41.5)

max diameter < 5cm

145 (59.9)

61 (57.5)

83 (61.5)

max diameter ≥ 5cm

75 (31.0)

34 (32.1)

41 (30.4)

2

supplementary Table S11. Models/individual markers performance in subsets

model/ marker

subset

HCC or CLD patients, entire dataset

HCC or CLD patients, with an HCV etiology

HCC or CLD patients, with an HBV etiology

HCCvsCLD

AUC(95%CI)

sen spe ppv npv ccp

HCCvsCLD

AUC(95%CI)

sen spe ppv npv ccp

HCCvsCLD

AUC(95%CI)

sen spe ppv npv ccp

GALAD

unifocal < 2cm

29 vs. 283

0.783(0.698-0.868)

62.1 79.9 24.0 95.4 78.2

6 vs. 133

0.789(0.598-0.981)

66.7 81.2 13.8 98.2 80.6

23 vs. 149

0.772(0.677-0.866)

60.9 78.5 30.4 92.9 76.2

GALAD

unifocal < 3cm

55 vs. 283

0.789(0.729-0.850)

60.0 79.9 36.7 91.1 76.6

14 vs. 133

0.807(0.694-0.920)

57.1 81.2 24.2 94.7 78.9

40 vs. 149

0.775(0.702-0.849)

60.0 78.5 42.9 88.0 74.6

GALAD

unifocal < 4cm

71 vs. 283

0.819(0.768-0.870)

66.2 79.9 45.2 90.4 77.1

21 vs. 133

0.840(0.755-0.926)

66.7 81.2 35.9 93.9 79.2

49 vs. 149

0.805(0.739-0.870)

65.3 78.5 50.0 87.3 75.3

GALAD

unifocal < 5cm

81 vs. 283

0.814(0.763-0.864)

64.2 79.9 47.7 88.6 76.4

26 vs. 133

0.849(0.774-0.925)

69.2 81.2 41.9 93.1 79.2

54 vs. 149

0.794(0.728-0.860)

61.1 78.5 50.8 84.8 73.9

GALAD

unifocal < 10cm

97 vs. 283

0.830(0.785-0.875)

68.0 79.9 53.7 87.9 76.8

32 vs. 133

0.872(0.807-0.937)

75.0 81.2 49.0 93.1 80.0

64 vs. 149

0.806(0.745-0.867)

64.1 78.5 56.2 83.6 74.2

GALAD


86 vs. 283

0.810(0.761-0.859)

62.8 79.9 48.6 87.6 75.9

29 vs. 133

0.855(0.784-0.926)

69.0 81.2 44.4 92.3 79.0

56 vs. 149

0.785(0.719-0.850)

58.9 78.5 50.8 83.6 73.2

GALAD

max diameter < 5cm

145 vs. 283

0.855(0.819-0.892)

74.5 79.9 65.5 85.9 78.0

61 vs. 133

0.910(0.868-0.952)

82.0 81.2 66.7 90.8 81.4

83 vs. 149

0.816(0.761-0.871)

68.7 78.5 64.0 81.8 75.0

GALAD


75 vs. 283

0.960(0.937-0.982)

94.7 79.9 55.5 98.3 83.0

34 vs. 133

0.990(0.978-1.000)

100 81.2 57.6 100 85.0

41 vs. 149

0.935(0.895-0.974)

90.2 78.5 53.6 96.7 81.1

GALAD-C

unifocal < 2cm

29 vs. 283

0.788(0.704-0.872)

51.7 85.9 27.3 94.6 82.7

6 vs. 133

0.783(0.605-0.961)

50.0 83.5 12.0 97.4 82.0

23 vs. 149

0.807(0.715-0.898)

52.2 87.9 40.0 92.3 83.1

GALAD-C

unifocal < 3cm

55 vs. 283

0.808(0.746-0.871)

58.2 85.9 44.4 91.4 81.4

14 vs. 133

0.858(0.750-0.966)

71.4 83.5 31.2 96.5 82.3

40 vs. 149

0.811(0.737-0.885)

55.0 87.9 55.0 87.9 81.0

GALAD-C

unifocal < 4cm

71 vs. 283

0.844(0.792-0.896)

64.8 85.9 53.5 90.7 81.6

21 vs. 133

0.885(0.806-0.963)

71.4 83.5 40.5 94.9 81.8

49 vs. 149

0.843(0.779-0.907)

63.3 87.9 63.3 87.9 81.8

GALAD-C

unifocal < 5cm

81 vs. 283

0.844(0.795-0.893)

64.2 85.9 56.5 89.3 81.0

26 vs. 133

0.892(0.824-0.961)

73.1 83.5 46.3 94.1 81.8

54 vs. 149

0.838(0.775-0.900)

61.1 87.9 64.7 86.2 80.8

GALAD-C

unifocal < 10cm

97 vs. 283

0.865(0.822-0.908)

69.1 85.9 62.6 89.0 81.6

32 vs. 133

0.912(0.854-0.970)

78.1 83.5 53.2 94.1 82.4

64 vs. 149

0.857(0.801-0.912)

65.6 87.9 70.0 85.6 81.2

GALAD-C


86 vs. 283

0.841(0.794-0.889)

61.6 85.9 57.0 88.0 80.2

29 vs. 133

0.895(0.831-0.959)

72.4 83.5 48.8 93.3 81.5

56 vs. 149

0.832(0.770-0.894)

57.1 87.9 64.0 84.5 79.5

GALAD-C

max diameter < 5cm

145 vs. 283

0.889(0.856-0.921)

73.8 85.9 72.8 86.5 81.8

61 vs. 133

0.938(0.903-0.973)

86.9 83.5 70.7 93.3 84.5

83 vs. 149

0.866(0.818-0.915)

65.1 87.9 75.0 81.9 79.7

GALAD-C


75 vs. 283

0.983(0.969-0.998)

96.0 85.9 64.3 98.8 88.0

34 vs. 133

0.999(0.997-1.000)

100 83.5 60.7 100 86.8

41 vs. 149

0.972(0.948-0.997)

92.7 87.9 67.9 97.8 88.9

GAAP

unifocal < 2cm

29 vs. 283

0.786(0.705-0.866)

62.1 79.2 23.4 95.3 77.6

6 vs. 133

0.799(0.635-0.964)

50.0 72.9 7.69 97.0 71.9

23 vs. 149

0.804(0.717-0.892)

65.2 84.6 39.5 94.0 82.0

GAAP

unifocal < 3cm

55 vs. 283

0.805(0.744-0.865)

63.6 79.2 37.2 91.8 76.6

14 vs. 133

0.866(0.767-0.966)

71.4 72.9 21.7 96.0 72.8

40 vs. 149

0.808(0.735-0.880)

60.0 84.6 51.1 88.7 79.4

GAAP

unifocal < 4cm

71 vs. 283

0.840(0.790-0.891)

71.8 79.2 46.4 91.8 77.7

21 vs. 133

0.885(0.812-0.958)

81.0 72.9 32.1 96.0 74.0

49 vs. 149

0.840(0.777-0.902)

67.3 84.6 58.9 88.7 80.3

GAAP

unifocal < 5cm

81 vs. 283

0.841(0.793-0.889)

71.6 79.2 49.6 90.7 77.5

26 vs. 133

0.892(0.827-0.958)

80.8 72.9 36.8 95.1 74.2

54 vs. 149

0.836(0.774-0.897)

66.7 84.6 61.0 87.5 79.8

GAAP

unifocal < 10cm

97 vs. 283

0.862(0.820-0.905)

76.3 79.2 55.6 90.7 78.4

32 vs. 133

0.912(0.857-0.967)

84.4 72.9 42.9 95.1 75.2

64 vs. 149

0.854(0.799-0.909)

71.9 84.6 66.7 87.5 80.8

GAAP


86 vs. 283

0.840(0.793-0.887)

70.9 79.2 50.8 90.0 77.2

29 vs. 133

0.895(0.834-0.956)

82.8 72.9 40.0 95.1 74.7

56 vs. 149

0.832(0.772-0.893)

64.3 84.6 61.0 86.3 79.0

GAAP

max diameter < 5cm

145 vs. 283

0.882(0.849-0.915)

80.7 79.2 66.5 88.9 79.7

61 vs. 133

0.935(0.900-0.970)

91.8 72.9 60.9 95.1 78.9

83 vs. 149

0.861(0.812-0.909)

72.3 84.6 72.3 84.6 80.2

GAAP


75 vs. 283

0.982(0.966-0.997)

98.7 79.2 55.6 99.6 83.2

34 vs. 133

0.998(0.994-1.000)

100 72.9 48.6 100 78.4

41 vs. 149

0.970(0.944-0.996)

97.6 84.6 63.5 99.2 87.4

PIVKA-II

unifocal < 2cm

29 vs. 283

0.746(0.658-0.835)

62.1 74.2 19.8 95.0 73.1

6 vs. 133

0.748(0.500-0.996)

66.7 75.2 10.8 98.0 74.8

23 vs. 149

0.744(0.649-0.838)

60.9 73.8 26.4 92.4 72.1

PIVKA-II

unifocal < 3cm

55 vs. 283

0.759(0.690-0.828)

65.5 74.2 33.0 91.7 72.8

14 vs. 133

0.819(0.694-0.945)

78.6 75.2 25.0 97.1 75.5

40 vs. 149

0.734(0.650-0.819)

60.0 73.8 38.1 87.3 70.9

PIVKA-II

unifocal < 4cm

71 vs. 283

0.794(0.735-0.853)

70.4 74.2 40.7 90.9 73.4

21 vs. 133

0.825(0.726-0.924)

76.2 75.2 32.7 95.2 75.3

49 vs. 149

0.779(0.704-0.854)

67.3 73.8 45.8 87.3 72.2

PIVKA-II

unifocal < 5cm

81 vs. 283

0.802(0.748-0.856)

72.8 74.2 44.7 90.5 73.9

26 vs. 133

0.833(0.746-0.920)

76.9 75.2 37.7 94.3 75.5

54 vs. 149

0.785(0.715-0.856)

70.4 73.8 49.4 87.3 72.9

PIVKA-II

unifocal < 10cm

97 vs. 283

0.827(0.779-0.875)

77.3 74.2 50.7 90.5 75.0

32 vs. 133

0.861(0.787-0.935)

81.2 75.2 44.1 94.3 76.4

64 vs. 149

0.809(0.746-0.872)

75.0 73.8 55.2 87.3 74.2

PIVKA-II


86 vs. 283

0.801(0.748-0.854)

72.1 74.2 45.9 89.7 73.7

29 vs. 133

0.839(0.759-0.920)

75.9 75.2 40.0 93.5 75.3

56 vs. 149

0.781(0.711-0.851)

69.6 73.8 50.0 86.6 72.7

PIVKA-II

max diameter < 5cm

145 vs. 283

0.827(0.787-0.868)

76.6 74.2 60.3 86.1 75.0

61 vs. 133

0.886(0.837-0.935)

85.2 75.2 61.2 91.7 78.4

83 vs. 149

0.786(0.726-0.845)

69.9 73.8 59.8 81.5 72.4

PIVKA-II


75 vs. 283

0.969(0.946-0.993)

97.3 74.2 50.0 99.1 79.1

34 vs. 133

0.994(0.986-1.000)

100 75.2 50.7 100 80.2

41 vs. 149

0.950(0.908-0.991)

95.1 73.8 50.0 98.2 78.4

AFP

unifocal < 2cm

29 vs. 283

0.692(0.584-0.799)

62.1 72.1 18.6 94.9 71.2

6 vs. 133

0.852(0.741-0.963)

83.3 73.7 12.5 99.0 74.1

23 vs. 149

0.652(0.529-0.774)

56.5 70.5 22.8 91.3 68.6

AFP

unifocal < 3cm

55 vs. 283

0.684(0.606-0.763)

54.5 72.1 27.5 89.1 69.2

14 vs. 133

0.712(0.546-0.878)

57.1 73.7 18.6 94.2 72.1

40 vs. 149

0.668(0.576-0.760)

52.5 70.5 32.3 84.7 66.7

AFP

unifocal < 4cm

71 vs. 283

0.703(0.635-0.772)

56.3 72.1 33.6 86.8 68.9

21 vs. 133

0.729(0.607-0.850)

52.4 73.7 23.9 90.7 70.8

49 vs. 149

0.691(0.606-0.776)

57.1 70.5 38.9 83.3 67.2

AFP

unifocal < 5cm

81 vs. 283

0.688(0.622-0.753)

51.9 72.1 34.7 84.0 67.6

26 vs. 133

0.696(0.584-0.808)

46.2 73.7 25.5 87.5 69.2

54 vs. 149

0.683(0.601-0.765)

53.7 70.5 39.7 80.8 66.0

AFP

unifocal < 10cm

97 vs. 283

0.697(0.634-0.759)

53.6 72.1 39.7 81.9 67.4

32 vs. 133

0.724(0.617-0.831)

53.1 73.7 32.7 86.7 69.7

64 vs. 149

0.681(0.603-0.760)

53.1 70.5 43.6 77.8 65.3

AFP


86 vs. 283

0.679(0.615-0.742)

51.2 72.1 35.8 82.9 67.2

29 vs. 133

0.694(0.587-0.802)

48.3 73.7 28.6 86.7 69.1

56 vs. 149

0.669(0.589-0.750)

51.8 70.5 39.7 79.5 65.4

AFP

max diameter < 5cm

145 vs. 283

0.730(0.681-0.780)

60.7 72.1 52.7 78.2 68.2

61 vs. 133

0.772(0.701-0.844)

63.9 73.7 52.7 81.7 70.6

83 vs. 149

0.703(0.635-0.771)

57.8 70.5 52.2 75.0 65.9

AFP


75 vs. 283

0.793(0.729-0.856)

70.7 72.1 40.2 90.3 71.8

34 vs. 133

0.827(0.728-0.925)

76.5 73.7 42.6 92.5 74.3

41 vs. 149

0.769(0.684-0.853)

65.9 70.5 38.0 88.2 69.5

AFP-L3%

unifocal < 2cm

29 vs. 283

0.638(0.519-0.758)

41.4 84.5 21.4 93.4 80.4

6 vs. 133

0.709(0.451-0.967)

50.0 89.5 17.6 97.5 87.8

23 vs. 149

0.604(0.469-0.740)

39.1 79.9 23.1 89.5 74.4

AFP-L3%

unifocal < 3cm

55 vs. 283

0.610(0.522-0.699)

36.4 84.5 31.2 87.2 76.6

14 vs. 133

0.671(0.497-0.845)

42.9 89.5 30.0 93.7 85.0

40 vs. 149

0.579(0.474-0.684)

35.0 79.9 31.8 82.1 70.4

AFP-L3%

unifocal < 4cm

71 vs. 283

0.631(0.553-0.710)

40.8 84.5 39.7 85.1 75.7

21 vs. 133

0.670(0.527-0.813)

42.9 89.5 39.1 90.8 83.1

49 vs. 149

0.606(0.511-0.702)

40.8 79.9 40.0 80.4 70.2

AFP-L3%

unifocal < 5cm

81 vs. 283

0.619(0.544-0.693)

38.3 84.5 41.3 82.7 74.2

26 vs. 133

0.648(0.517-0.778)

38.5 89.5 41.7 88.1 81.1

54 vs. 149

0.598(0.505-0.691)

38.9 79.9 41.2 78.3 69.0

AFP-L3%

unifocal < 10cm

97 vs. 283

0.645(0.576-0.713)

42.3 84.5 48.2 81.0 73.7

32 vs. 133

0.689(0.573-0.806)

43.8 89.5 50.0 86.9 80.6

64 vs. 149

0.617(0.530-0.703)

42.2 79.9 47.4 76.3 68.5

AFP-L3%


86 vs. 283

0.602(0.529-0.675)

34.9 84.5 40.5 81.0 72.9

29 vs. 133

0.646(0.521-0.770)

37.9 89.5 44.0 86.9 80.2

56 vs. 149

0.573(0.482-0.664)

33.9 79.9 38.8 76.3 67.3

AFP-L3%

max diameter < 5cm

145 vs. 283

0.669(0.610-0.727)

46.9 84.5 60.7 75.6 71.7

61 vs. 133

0.737(0.652-0.822)

54.1 89.5 70.2 81.0 78.4

83 vs. 149

0.617(0.538-0.696)

42.2 79.9 53.8 71.3 66.4

AFP-L3%


75 vs. 283

0.782(0.710-0.853)

65.3 84.5 52.7 90.2 80.4

34 vs. 133

0.828(0.730-0.925)

67.6 89.5 62.2 91.5 85.0

41 vs. 149

0.739(0.638-0.841)

63.4 79.9 46.4 88.8 76.3

Note: AUC=area under receiver operating characteristic curve; PPV= Positive Predictive Value; NPV= Negative Predictive Value. Ccp, correctedly classfied %

web viewparameter estimates (se) and or (95% ci) of variables by logistic regression in galad-c and...

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