Table 3 Predictive factors of HCC development during entecavir treatment.

From: Soluble programmed cell death-1 predicts hepatocellular carcinoma development during nucleoside analogue treatment

Factor

Category

Univariate analysis

Multivariate analysis

HR

95% CI

p-value

HR

95% CI

p-value

Clinical factor

Age (years)

 ≥ 49

7.458

1.652

33.669

0.0090*

    

Sex

Male

0.839

0.274

2.569

0.76

    

Body mass index (kg/m2)

 ≥ 21.9

2.665

0.733

9.691

0.14

    

Cirrhosis

(+)

8.008

2.611

24.562

0.0003*

    

HCC family history

(+)

1.979

0.438

8.936

0.38

    

Previous interferon treatment

(+)

1.128

0.310

4.103

0.85

    

Alcohol consumption

(+)

1.621

0.445

5.902

0.46

    

Cigarette smoking

(+)

1.154

0.377

3.530

0.80

    

Diabetes mellitus

(+)

2.836

0.627

12.828

0.18

    

Fatty liver

(+)

0.196

0.025

1.506

0.12

    

Platelet count (×103/mm3)

≤ 117

9.546

2.928

31.127

0.0002*

    

Aspartate aminotransferase (U/L)

≤ 80

1.517

0.467

4.931

0.49

    

Alanine aminotransferase (U/L)

≤ 81

3.058

0.941

9.936

0.063

    

γ-glutamyltransferase (U/L)

≥ 40

2.082

0.573

7.565

0.27

    

Total bilirubin (mg/dL)

≥ 0.9

2.268

0.742

6.934

0.15

    

Albumin (g/dL)

≤ 4.1

2.847

0.783

10.352

0.11

    

Prothrombin time (%)

≤ 84

2.535

0.740

8.680

0.14

    

α-fetoprotein (ng/mL)

≥ 6.4

5.812

1.288

26.231

0.022*

5.524

1.084

28.164

0.040*

HBV genotype

C

0.847

0.187

3.837

0.83

    

HBeAg

Positivity

1.491

0.500

4.447

0.47

    

HBsAg (log IU/mL)

≤ 3.53

5.507

1.220

24.859

0.027*

    

HBV-DNA (log copies/mL)

≤ 6.9

2.264

0.696

7.362

0.17

    

Precore

G1896A

1.230

0.402

3.764

0.72

    

Basic core promoter

A1762T/G1764A

1.070

0.289

3.962

0.92

    

Hyaluronic acid (ng/mL)

≥ 143

3.922

1.281

12.008

0.017*

    

Type III procollagen-N-peptide (U/mL)

≥ 0.9

1.770

0.579

5.414

0.32

    

Type IV collagen (ng/mL)

≥ 200

5.300

1.458

19.270

0.011*

    

M2BPGi (C.O.I)

≥ 1.71

2.286

0.767

6.811

0.14

    

AST to platelet ratio index

≥ 1.58

3.108

0.954

10.127

0.060

    

Fibrosis-4 index

≥ 4.08

10.117

3.093

33.089

0.0001*

    

Soluble immune checkpoint proteins

sBTLA (pg/mL)

≥ 100.68

2.093

0.641

6.831

0.22

    

sCD27 (pg/mL)

≤ 2262.18

2.175

0.668

7.079

0.20

    

sCD28 (pg/mL)

≥ 1705.07

2.584

0.711

9.393

0.15

    

sTIM-3 (pg/mL)

≤ 3184.99

1.861

0.573

6.048

0.30

    

sHVEM (pg/mL)

≤ 2470.83

3.078

1.006

9.416

0.049*

    

sCD40 (pg/mL)

≤ 493.68

4.518

1.000

20.405

0.050

    

sGITR (pg/mL)

≤ 0.49

2.984

0.661

13.476

0.16

    

sLAG-3 (pg/mL)

≤ 11,206.70

1.704

0.524

5.539

0.38

    

sTLR-2 (pg/mL)

≤ 321.19

2.554

0.786

8.301

0.12

    

sGITRL (pg/mL)

≤ 26.52

2.429

0.747

7.892

0.14

    

sPD-1 (pg/mL)

≤ 447.27

3.393

1.044

11.033

0.042*

4.537

1.363

15.103

0.014*

sCTLA-4 (pg/mL)

≥ 12.63

3.461

0.766

15.631

0.11

    

sCD80 (pg/mL)

≥ 12.99

1.752

0.573

5.359

0.33

    

sCD86 (pg/mL)

≥ 310.61

2.511

0.690

9.143

0.16

    

sPD-L1 (pg/mL)

≤ 24.67

2.435

0.670

8.856

0.18

    

sICOS (pg/mL)

≥ 164.71

3.713

1.210

11.393

0.022*

    
  1. *p < 0.05. HCC, hepatocellular carcinoma.
  2. HBV, hepatitis B virus; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; sBTLA, soluble B- and T-lymphocyte attenuator; sCD27, soluble CD27; sCD28, soluble CD28; sTIM-3, soluble T-cell immunoglobulin and mucin domain-3; sHVEM, soluble herpes virus entry mediator; sCD40, soluble CD40; sGITR, soluble glucocorticoid-induced TNFR-related; sLAG-3, soluble lymphocyte-activation gene 3; sTLR-2, soluble toll-like receptor 2; sGITRL, soluble glucocorticoid-induced TNFR-related ligand; sPD-1, soluble programmed cell death-1; sCTLA-4, soluble cytotoxic T-lymphocyte-associated antigen 4; sCD80, soluble CD80; sCD86, soluble CD86; sPD-L1, soluble programmed cell death-ligand 1; sICOS, soluble inducible T-cell co-stimulator.
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