supplementary table 1. study characteristics: an overview of...

Supplementary Table 1. Study characteristics: An overview of studies regarding APRI for prediction of varices in liver cirrhosis.

First

author

(Year)

RegionsStudy

description

No.

total

Pts

Age (year)Male

(%)

Etiology of

cirrhosis

HCC

(%)

Child-Pugh

class (%)

No. Pts

who

underwent

endoscopy

Location

of

varices

Prevalenc

e of

varices

(%)

Prevalence

of large

varices (%)

Definitions of large

varices

Cut-off

of

varices/

large

varices

QUADAS

Score

Morishita

(2014)Japan NA 92 68.7±9.3 51.1% HCV 100% 50.0%

A 65.2 %

B 32.6 %

C 2.2 %

92 EV 51.1% 33.7%

Straight small-

calibered varices with

red color signs;

moderately enlarged,

beady varices;

markedly enlarged,

nodular, or tumor-

shaped varices.

1.5 /

1.6210

Salzl

(2014)Austria Prospective 88 NA NA

Viral 32%,

alcohol 49%,

viral+alcohol

7%,

cryptogenic or

others 12%

NA

A 17%

B 66%

C 17%

88 EV 69.3% 39.8% NA1.906 /

NA8

Calvaruso

(2013)Italy Prospective 96 63.2±9.5 69.8% HCV 100% 0.0% A 100% 96 EV 56.3% 27.1%

>30% of the lumen

was occupied.

1.5 /

210

Feng

(2013)China Prospective 89

55.04±11.1

178.7%

HBV 71.9%,

HCV 3.4%,

alcohol 7.9%,

cryptogenic or

others 16.9%

0.0% NA 89 EV/GV 66.3% 30.3%

Tortuous varices with

red color signs; beady,

nodular, or tumor-

shaped varices with or

without red color signs.

0.93 /

1.0211

Zambam

de Mattos

(2013)

BrazilRetrospective

cross-sectional164 56.7 59.8%

HCV 54.88%,

alcohol 38.41%,

others 6.7%

NA

A 52.44%

B/C

47.56%

164 EV 72.6% NA NA1.3 /

NA8

Pai

(2012)India

Prospective

(abstract)114 NA NA NA NA NA 114 EV NA 48.2% NA

NA /

150.568

Wang

(2012)China Prospective 126 54.5±10.1 73.8% HBV 100% 0.0% A 100% 126 EV 38.1% 10.3%

Small varices of red

color, and medium or

large varices.

0.77 /

1.2410

Reed

(2011)England NA (abstract) 96 NA NA

HCV 28.1%,

alcohol 27.1%,

cryptogenic or

others 44.8%

NA NA 96 EV 26.0% 13.5% NANA /

NA8

Stefanesc

u

(2011)

Romania Cross-sectional 23155.6

6±9.51958.4%

HCV 49.78%,

alcohol 38.96%,

viral+alcohol

11.26%

NA

A 75.9%

B 18.4%

C 5.7%

231 EV 68.0% 29.5%

Enlarged, tortuous EV

occupying <1/3 of the

lumen; large, coil-

shaped EV occupying

>1/3 of the lumen.

1.434 /

2.20110

Tafarel

(2011)Brazil Prospective 300 53.1±12.15 64.3%

Viral 49%,

alcohol 24%,

viral+alcohol

5.33%,

cryptogenic or

others 21.67%

0.0%

A 70.7%

B 24.3%

C 5%

300 EV 57.0% 3.3%

Varices did not

disappear with air

insufflation and

occupied >1/3 of the

esophageal lumen.

1.64 /

NA10

Sebastiani

(2010)Italy Retrospective 510 59.5±11 58.0%

HBV 8.8%,

HCV 55.1%,

alcohol 30.4%,

0.0%

A 79.4%

B 16.7%

C 3.9%

510 EV 56.9% 19.0%

Non-confluent EV

protruding in the lumen

despite insufflation;

1.4 /

1.512

cryptogenic or

others 5.7%

confluent thick EV,

gastroesophageal

junction varices and

isolated GVs.

Castéra

(2009)France Prospective 70 54.1±11.8 60.0% HCV 100% NA A 100% 70 EV 35.7% 18.6% NA

1.3 /

1.39

Abbreviations: EV,esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.

Supplementary Table 2. Study quality: An overview of studies regarding APRI for prediction of varices in liver cirrhosis.

No. ItemSalz

l Calvaruso

Zambam de

MattosMorishita Wang Tafarel Stefanescu Sebastiani Castéra Pai

Ree

d Feng

1Was the spectrum of patients representative of the patients

who will receive the test in practice?Y N U N N N N Y N U Y Y

2 Were selection criteria clearly described? Y Y N Y Y Y Y Y Y N U Y

3Is the reference standard likely to correctly classify the target

condition?Y Y Y Y Y Y Y Y Y Y Y Y

4

Is the time period between reference standard and index test

short enough to be reasonably sure that the target condition

did not change between the two tests? (≤3 months)

U Y N U U Y U Y U Y U U

5Did the whole sample or a random selection of the sample,

receive verification using a reference standard of diagnosis?Y Y Y Y Y Y Y Y Y Y Y Y

6Did patients receive the same reference standard regardless

of the index test result?Y Y Y Y Y Y Y Y Y Y Y Y

7

Was the reference standard independent of the index test

(i.e. the index test did not form part of the reference

standard)?

Y Y Y Y Y Y Y Y Y Y Y Y

8Was the execution of the index test described in sufficient

detail to permit replication of the test?Y N Y Y Y N Y Y Y N N Y

9Was the execution of the reference standard described in

sufficient detail to permit its replication?N Y N Y Y Y Y Y N N N Y

10Were the index test results interpreted without knowledge of

the results of the reference standard?U U U U U U U U U U U U

11Were the reference standard results interpreted without

knowledge of the results of the index test?U U U U U U U U U U U U

12

Were the same clinical data available when test results were

interpreted as would be available when the test is used in

practice?

Y Y Y Y Y Y Y Y Y Y Y Y

13 Were uninterpretable/ intermediate test results reported? U Y Y Y Y Y Y Y Y Y Y Y

14 Were withdrawals from the study explained? N Y Y Y Y Y Y Y Y Y Y Y

　 Score 8 10 8 10 10 10 10 12 9 8 8 11

Supplementary Table 3. An overview of studies regarding AAR for prediction of varices in liver cirrhosis.

First

author

(Year)

RegionsStudy

description

No.

total

Pts

Age

(year)

Male

(%)

Etiology of

cirrhosis

HCC

(%)

Child-Pugh

class (%)

No. Pts

who

underwent

endoscopy

Locatio

n of

varices

Prevalence

of varices

(%)

Prevalence

of large

varices (%)


varices

Cut-off of

varices/

large

varices

QUADAS

Score

Calvaruso

(2013)Italy Prospective 96 63.2±9.5 69.8% HCV 100% 0.0% A 100% 96 EV 56.3% 27.1%

>30% of the lumen

was occupied.0.8/ 1 10

Reed


HCV 28.1%,

alcohol 27.1%,

cryptogenic or

others 44.8%

NA NA 96 EV 26.0% 13.5% NA NA 8

Sebastiani

(2010)Italy

Retrospectiv

e510 59.5±11 58.0%

HBV 8.8%,

HCV 55.1%,

alcohol 30.4%,

cryptogenic or

others 5.7%

0.0%

A 79.4%

B 16.7%

C 3.9%

510 EV 56.9% 19.0%

Non-confluent EV

protruding in the

lumen despite

insufflation; confluent

thick EV,

gastroesophageal


isolated GVs.

1/ 1.1 12

Castéra

(2009)France Prospective 70 54.1±11.8 60.0% HCV 100% NA A 100% 70 EV 35.7% 18.6% NA 1/ 1 9

Abbreviations: EV, esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.

Supplementary Table 4. Study quality: An overview of studies regarding AAR for prediction of varices in liver

cirrhosis.

No

.Item Calvaruso Sebastiani Castéra Reed


who will receive the test in practice?N Y N Y

2 Were selection criteria clearly described? Y Y Y U


condition?Y Y Y Y

4




Y Y U U


receive verification using a reference standard of diagnosis?Y Y Y Y


of the index test result?Y Y Y Y

7Was the reference standard independent of the index test (i.e.

the index test did not form part of the reference standard)?Y Y Y Y


detail to permit replication of the test?N Y Y N


sufficient detail to permit its replication?Y Y N N


the results of the reference standard?U U U U


knowledge of the results of the index test?U U U U

12

Were the same clinical data available when test results were


practice?

Y Y Y Y

13 Were uninterpretable/ intermediate test results reported? Y Y Y Y

14 Were withdrawals from the study explained? Y Y Y Y

　 Score 10 12 9 8

Supplementary Table 5. Study characteristics: An overview of studies regarding FIB-4 for prediction of varices in liver cirrhosis.

First

author

(Year)

RegionsStudy

description

No.

total

Pts

Age

(year)

Male

(%)

Etiology of

cirrhosis

HCC

(%)

Child-Pugh

class (%)

No. Pts

who

underwent

endoscopy

Location

of

varices

Prevalence

of varices

(%)

Prevalenc

e of large

varices

(%)

Definitions of

large varices

Cut-off

of

varices/

large

varices

QUADAS

Score

Morishita

(2014)Japan NA 92 68.7±9.3 51.1% HCV 100% 50.0%

A 65.2 %

B 32.6 %

C 2.2 %

92 EV 51.1% 33.7%

Straight small-

calibered varices

with RC signs;

moderately

enlarged, beady

varices; markedly

enlarged, nodular,

or tumor-shaped

varices.

6.21/

7.710

Reed


HCV 28.1%,

alcohol 27.1%,

cryptogenic or

others 44.8%

NA NA 96 EV 26.0% 13.5% NANA/

NA7

Stefanesc

u

(2011)

Romania Cross-

sectional

231 55.6

6±9.519

58.4% HCV 49.78%,

alcohol 38.96%,

viral+alcohol

11.26%

NA A 75.9%

B 18.4%

C 5.7%

231 EV 68.0% 29.5% Enlarged, tortuous

EV occupying less

than one third of

the lumen; large,

coil-shaped EV

occupying more

than one third of

3.98/

6.7498

10

the lumen.

Sebastiani


HBV 8.8%,

HCV 55.1%,

alcohol 30.4%,

cryptogenic or

others 5.7%

0.0%

A 79.4%

B 16.7%

C 3.9%

510 EV 56.9% 19.0%

Non-confluent EV

protruding in the

lumen despite

insufflation;

confluent thick EV,

gastroesophageal

junction varices

and isolated

gastric varices.

3.5/

4.312

Hassan

(2014)Egypt Prospective 65

52.40 ±

6.1560.0% HCV 100% 0.0%

A 80.0%

B 20.0%65 EV 76.9% 49.2%

Enlarged, tortuous

EV occupying less

than one-third of

the lumen; large,

coil-shaped EV

occupying more

than one-third of

the lumen.

2.8/

3.310


Supplementary Table 6. Study quality: An overview of studies regarding FIB-4 for prediction of varices in liver cirrhosis.

No. Item Morishita Stefanescu Sebastiani Reed Hassan


who will receive the test in practice?N N Y Y N

2 Were selection criteria clearly described? Y Y Y U Y


condition?Y Y Y Y Y

4




U U Y U U


receive verification using a reference standard of diagnosis?Y Y Y Y Y


of the index test result?Y Y Y Y Y


the index test did not form part of the reference standard)?Y Y Y Y Y


detail to permit replication of the test?Y Y Y N Y


sufficient detail to permit its replication?Y Y Y N Y


the results of the reference standard?U U U U U


knowledge of the results of the index test?U U U U U

12Were the same clinical data available when test results were

interpreted as would be available when the test is used in Y Y Y U Y

practice?

13 Were uninterpretable/ intermediate test results reported? Y Y Y Y Y

14 Were withdrawals from the study explained? Y Y Y Y Y

　 Score 10 10 12 7 10

Supplementary Table 7. Study characteristics: An overview of studies regarding Lok for prediction of varices in liver cirrhosis.

First

author

(Year)

RegionsStudy

description

No.

total

Pts

Age

(year)

Male

(%)

Etiology of

cirrhosis

HCC

(%)

Child-Pugh

class (%)

No. Pts

who

underwent

endoscopy

Location

of

varices

Prevalence

of varices

(%)

Prevalence

of large

varices (%)


varices

Cut-off

of

varices/

large

varices

QUADAS

Score

Hassan


52.40 ±

6.1560.0% HCV 100%

0.0

%

A 80.0%

B 20.0%65 EV 76.9% 49.2%



lumen; large, coil-

shaped EV occupying

>1/3 of the lumen.

0.63/

0.710

Stefanescu

(2011)

Romania Cross-sectional 23155.6

6±9.51958.4%

HCV 49.78%,

alcohol

38.96%,

viral+alcohol

11.26%

NA

A 75.9%

B 18.4%

C 5.7%

231 EV 68.0% 29.5%



lumen; large, coil-

shaped EV occupying

>1/3 of the lumen.

0.62/

0.79610

Sebastiani


HBV 8.8%,

HCV 55.1%,

alcohol 30.4%,

cryptogenic or

others 5.7%

0.0

%

A 79.4%

B 16.7%

C 3.9%

510 EV 56.9% 19.0%

Non-confluent EV



confluent thick EV,

gastroesophageal


isolated GVs.

0.9/

1.512

Castéra

(2009)France Prospective 70 54.1±11.8 60.0% HCV 100% NA A 100% 70 EV 35.7% 18.6% NA

0.6/

0.69

Abbreviations: EV,esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.

Supplementary Table 8. Study quality: An overview of studies regarding Lok for prediction of varices in liver

cirrhosis.

No

.Item Stefanescu Sebastiani Hassan Castéra

1Was the spectrum of patients representative of the

patients who will receive the test in practice?N Y N N

2 Were selection criteria clearly described? Y Y Y Y

3Is the reference standard likely to correctly classify the

target condition?Y Y Y Y

4

Is the time period between reference standard and index

test short enough to be reasonably sure that the target

condition did not change between the two tests? (≤3

months)

U Y U U

5

Did the whole sample or a random selection of the sample,

receive verification using a reference standard of

diagnosis?

Y Y Y Y

6Did patients receive the same reference standard

regardless of the index test result?Y Y Y Y

7

Was the reference standard independent of the index test

(i.e. the index test did not form part of the reference

standard)?

Y Y Y Y


detail to permit replication of the test?Y Y Y Y


sufficient detail to permit its replication?Y Y Y N

10 Were the index test results interpreted without knowledge U U U U

of the results of the reference standard?


knowledge of the results of the index test?U U U U

12

Were the same clinical data available when test results

were interpreted as would be available when the test is

used in practice?

Y Y Y Y

13 Were uninterpretable/ intermediate test results reported? Y Y Y Y

14 Were withdrawals from the study explained? Y Y Y Y

　 Score 10 12 10 9

Supplementary Table 9. Study characteristics: An overview of studies regarding Forns score for prediction of varices in liver cirrhosis.

First

author

(Year)

RegionsStudy

description

No.

total

Pts

Age

(year)

Male

(%)

Etiology of

cirrhosis

HCC

(%)

Child-Pugh

class (%)

No. Pts

who

underwent

endoscopy

Locatio

n of

varices

Prevalence

of varices

(%)

Prevalence

of large

varices (%)


varices

Cut-off

of

varices/

large

varices

QUADAS

Score

Hassan


52.40 ±

6.1560.0% HCV 100% 0.0%

A 80.0%

B 20.0%65 EV 76.9% 49.2%



lumen; large, coil-shaped

EV occupying >1/3 of the

lumen.

6.61/

6.910

Stefanesc

u

(2011)

Romania Cross-sectional 231

55.6

6±9.51

9

58.4%

HCV 49.78%,

alcohol 38.96%,

viral+alcohol

11.26%

NA

A 75.9%

B 18.4%

C 5.7%

231 EV 68.0% 29.5%



lumen; large, coil-shaped

EV occupying >1/3 of the

lumen.

7.297/

8.53810

Sebastiani

(2010)Italy Retrospective 510

59.5±1

158.0%

HBV 8.8%,

HCV 55.1%,

alcohol 30.4%,

cryptogenic or

others 5.7%

0.0%

A 79.4%

B 16.7%

C 3.9%

510 EV 56.9% 19.0%

Non-confluent EV



confluent thick EV,

gastroesophageal


isolated GVs.

8.5/

8.812


Supplementary Table 10. Study quality: An overview of studies regarding Forns score for prediction of

varices in liver cirrhosis.

No. Item Stefanescu Sebastiani Hassan


who will receive the test in practice?N Y N

2 Were selection criteria clearly described? Y Y Y


condition?Y Y Y

4




U Y U


receive verification using a reference standard of diagnosis?Y Y Y


of the index test result?Y Y Y


the index test did not form part of the reference standard)?Y Y Y


detail to permit replication of the test?Y Y Y


sufficient detail to permit its replication?Y Y Y


the results of the reference standard?U U U


knowledge of the results of the index test?U U U

12 Were the same clinical data available when test results were Y Y Y


practice?

13 Were uninterpretable/intermediate test results reported? Y Y Y

14 Were withdrawals from the study explained? Y Y Y

　 Score 10 12 10

Supplementary Table 11. Study characteristics: An overview of studies regarding FibroIndex for prediction of varices in liver cirrhosis.

First

author

(Year)

RegionsStudy

description

No.

total

Pts

Age

(year)

Male

(%)

Etiology of

cirrhosis

HCC

(%)

Child-Pugh

class (%)

No. Pts

who

underwent

endoscopy

Location

of

varices

Prevalence

of varices

(%)

Prevalence

of large

varices (%)


varices

Cut-off of

varices/

large

varices

QUADAS

Score

Sebastiani

(2010)

ItalyRetrospectiv

e510 59.5±11 58.0%

HBV 8.8%,

HCV 55.1%,

alcohol 30.4%,

cryptogenic or

others 5.7%

0.0%

A 79.4%

B 16.7%

C 3.9%

510 EV 56.9% 19.0%

Non-confluent EV



confluent thick EV,

gastroesophageal junction

varices and isolated GVs.

2.2/

2.512


Supplementary Table 12. Study quality: An overview of studies regarding

FibroIndex for prediction of varices in liver cirrhosis.

No. Item Sebastiani


who will receive the test in practice?Y

2 Were selection criteria clearly described? Y


condition?Y

4




Y


receive verification using a reference standard of diagnosis?Y


of the index test result?Y


the index test did not form part of the reference standard)?Y


detail to permit replication of the test?Y


sufficient detail to permit its replication?Y


the results of the reference standard?U


knowledge of the results of the index test?U

12 Were the same clinical data available when test results were Y


practice?

13 Were uninterpretable/ intermediate test results reported? Y

14 Were withdrawals from the study explained? Y

　 Score 12

Supplementary Figure 1. Flowchart of study inclusion regarding APRI score.

Supplementary Figure 2. Flowchart of study inclusion regarding

AAR score.

Supplementary Figure 3. Flowchart of study inclusion regarding

FIB-4 score.

Supplementary Figure 4. Flowchart of study inclusion

regarding FI score.

Supplementary Figure 5. Flowchart

of study inclusion regarding King score.

Supplementary Figure 6. Flowchart

of study inclusion regarding Lok score.

regarding Forns score.


regarding FibroIndex score.

Supplementary Figure 9. Summary PLRs of APRI, AAR,

and Lok scores for the prediction of varices in liver cirrhosis. Panel A: APRI; panel B: AAR; panel C: Lok.

Supplementary Figure 10. Summary PLRs of APRI, AAR, FIB-4, Lok, and Forns scores for

the prediction of large varices in liver cirrhosis. Panel A: APRI; panel B: AAR; panel C: FIB-4; panel D: Lok; panel E: Forns.

Supplementary Figure 11. Summary NLRs of APRI, AAR, and Lok scores for the prediction of varices in liver cirrhosis.

Panel A: APRI; panel B: AAR; panel C: Lok.

Supplementary Figure 12. Summary NLRs of APRI, AAR, FIB-4, Lok, and Forns scores for

the prediction of large varices in liver cirrhosis. Panel A: APRI; panel B: AAR; panel C: FIB-4; panel D: Lok; panel E: Forns.

Supplementary Figure 13. Summary DORs of APRI, AAR, and Lok scores for the prediction of varices in liver

cirrhosis. Panel A: APRI; panel B: AAR; panel C: Lok.

Supplementary Figure 14. Summary DORs of APRI, AAR, FIB-4, Lok, and Forns scores

for the prediction of large varices in liver cirrhosis. Panel A: APRI; panel B: AAR; panel C: FIB-4; panel D: Lok; panel E: Forns.

supplementary table 1. study characteristics: an overview of...

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