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Table 2 Host and viral risk factors for post-sustained virologic response (SVR) hepatocellular carcinoma (HCC) development (summarized from multivariable Cox regression models)

From: Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals

Risk factor

 

Variable

n

Country

Follow-up, median, years

Hazard ratio

95% CI

P value

Reference

Host factor

Fibrosis

        
 

Pre-SVR

        
  

Histological stage F2-4

562

Japan

4.8

10.7

2.2–192.1

<0.001

[53]

  

Histological stage, F3-4

1273

Japan

1.1

9.0

2.3–35.2

0.002

[34]

  

Histological stage, F3-4

1094

Japan

4.2

3.2

1.6–7.2

<0.001

[58]

  

Histological stage, F3-4

376

Taiwan

7.6

12.8

1.6–101.9

0.021

[56]

  

Histological stage, F3-4

871

Taiwan

3.4

4.0

1.5–10.7

0.007

[51]

  

Platelet, < 150 × 103/mm3

1056

Japan

4.7

2.8

1.1–7.2

0.04

[68]

  

Platelet, < 150 × 103/mm3

871

Taiwan

3.4

2.8

1.2–6.4

0.015

[51]

  

Platelet, < 150 × 103/mm3

1000

Europe and Canada

5.7

1.1

1.0–1.1

0.029

[61]

  

Albumin, < 35 g/dL

399

Sweden

7.8

4.4

1.3–14.7

0.016

[69]

  

Liver cirrhosis, yes

1351

Taiwan

4.0

8.4

4.1–17.0

<0.001

[70]

  

Liver cirrhosis, yes

4663

Canada

5.6

3.2

1.2–9.0

[71]

 

Post-SVR

        
  

FIB-4 index, high

522

Japan

7.2

1.7

1.1–2.9

0.02

[55]

  

APRI ≥ 0.7

1351

Taiwan

4.0

2.9

1.5–5.7

0.002

[70]

  

Elastography liver stiffness > 12 kPa

376

Taiwan

7.6

6.3

2.1–19.5

0.001

[56]

  

Liver cirrhosis, yes

10,738

USA

2.8

6.7

4.3–10.4

<0.001

[36]

  

Platelet, < 130 × 103/mm3

571

Japan

9.0

3.9

1.5–10.1

0.004

[72]

 

Age, years

≥50

562

Japan

4.8

4.1

1.4–17.4

<0.01

[53]

  

≥55

571

Japan

9.0

3.6

1.4–9.6

0.009

[72]

  

≥60

642

Taiwan

4.4

3.7

1.3–10.2

0.012

[52]

  

≥60

871

Taiwan

3.4

3.8

1.7–8.4

0.001

[51]

  

≥60

4663

Canada

5.6

4.4

1.3–15.3

[71]

  

>60

1094

Japan

4.2

3.1

1.3–6.6

0.009

[58]

  

>60

1056

Japan

4.7

3.1

1.3–7.4

0.01

[68]

  

>60

1000

Europe and Canada

5.7

9.8

1.2–77.8

0.031

[61]

  

≥65

1425

Japan

3.3

5.8

1.1–30.1

0.036

[54]

  

≥65

1351

Taiwan

4.0

2.7

1.2–6.3

0.017

[70]

  

≥65

10,738

USA

2.8

4.5

2.0–10.4

<0.001

[36]

  

Older

589

Taiwan

4.7

1.1

1.0–1.1

0.046

[73]

 

Sex

Male

1094

Japan

4.2

12.0

2.8–50.0

<0.001

[58]

  

Male

4663

Canada

5.6

3.3

1.1–9.6

[71]

  

Male

571

Japan

9.0

7.6

1.7–33.1

0.007

[72]

 

Diabetes

Yes

522

Japan

7.2

2.1

1.1–4.0

0.045

[55]

  

Yes

376

Taiwan

7.6

4.0

1.3–12.1

0.021

[56]

  

Yes

399

Sweden

7.8

3.2

1.1–9.6

0.035

[69]

  

Yes

10,738

USA

2.8

1.9

1.2–2.9

0.005

[36]

  

Yes

1000

Europe and Canada

5.7

2.3

1.0–5.3

0.057

[61]

  

Yes

4663

Canada

5.6

1.6

0.6–4.0

[71]

  

Yes

589

Taiwan

4.7

3.8

1.4–10.1

0.008

[73]

 

Elixhauser comorbidity index

Yes (≥1)

4663

Canada

5.6

2.2

1.0–5.1

[71]

 

Alpha-fetoprotein, ng/mL

        
 

Pre-SVR

≥8

562

Japan

4.8

2.6

1.2–6.1

<0.05

[53]

  

≥15

1351

Taiwan

4.0

1.9

1.0–3.6

0.038

[70]

  

≥20

871

Taiwan

3.4

3.2

1.6–6.2

0.001

[51]

 

Post-SVR

≥5

1425

Japan

3.3

8.1

2.7–23.9

<0.001

[54]

  

≥5

571

Japan

9.0

3.6

1.4–9.6

0.009

[72]

  

≥15

1351

Taiwan

4.0

2.3

1.0–5.3

0.043

[70]

  

≥10

1094

Japan

4.2

7.8

2.9–16.8

<0.001

[58]

 

Race/ethnicity

Hispanic

10,738

USA

2.8

2.3

1.1–4.8

0.032

[36]

 

Alcohol abuse

Yes

562

Japan

4.8

3.9

1.7–9.0

<0.01

[53]

  

Yes

10,738

USA

2.8

1.7

1.1–2.6

0.021

[36]

  

Yes

4663

Canada

5.6

1.1

0.34–3.3

[71]

 

Illicit drug use

Yes

4663

Canada

5.6

3.7

1.0–14.3

[71]

 

AST

>100 IU/L

1056

Japan

4.7

3.1

1.3–7.3

0.01

[68]

 

AST/ALT ratio

>0.72

1000

Europe and Canada

5.7

1.0

1.0–1.1

0.068

[61]

 

GGT

>75 U/L

642

Taiwan

4.4

6.4

2.2–18.9

0.001

[52]

Viral factor

Genotype 1b with Gln70 (His70) variant

 

1273

Japan

1.1

10.5

2.9–38.2

<0.001

[34]

 

Genotype 3

 

10,738

USA

2.8

1.6

1.0–2.7

0.071

[36]

 

Genotype 3

 

4663

Canada

5.6

1.4

0.58–3.4

[71]

  1. All data are from interferon-based studies
  2. APRI aspartate aminotransferase-to-platelet ratio index, ALT alanine aminotransferase, AST aspartate aminotransferase, FIB-4 fibrosis-4, GGT gamma-glutamyl transpeptidase, HCV hepatitis C virus, HCC hepatocellular carcinoma, SVR sustained virologic response