Supplementary Table 1. Study characteristics: An overview ...



Supplementary Table 1. Study characteristics: An overview of studies regarding APRI for prediction of varices in liver cirrhosis.First author (Year)RegionsStudy descriptionNo. total PtsAge (year)Male (%)Etiology of cirrhosis HCC (%)Child-Pugh class (%)No. Pts who underwent endoscopyLocation of varicesPrevalence of varices (%)Prevalence of large varices (%)Definitions of large varicesCut-off of varices/large varicesQUADAS ScoreMorishita (2014)JapanNA9268.7±9.351.1%HCV 100%50.0%A 65.2 %B 32.6 %C 2.2 %92EV51.1%33.7%Straight small-calibered varices with red color signs; moderately enlarged, beady varices; markedly enlarged, nodular, or tumor-shaped varices.1.5 /1.6210Salzl (2014)AustriaProspective88NANAViral 32%, alcohol 49%,viral+alcohol 7%, cryptogenic or others 12%NAA 17%B 66%C 17%88EV69.3%39.8%NA1.906 /NA8Calvaruso (2013)ItalyProspective9663.2±9.569.8%HCV 100%0.0%A 100%96EV56.3%27.1%>30% of the lumen was occupied.1.5 /210Feng (2013)ChinaProspective 8955.04±11.1178.7%HBV 71.9%, HCV 3.4%, alcohol 7.9%,cryptogenic or others 16.9%0.0%NA89EV/GV66.3%30.3%Tortuous varices with red color signs; beady, nodular, or tumor-shaped varices with or without red color signs.0.93 /1.0211Zambam de Mattos (2013)BrazilRetrospective cross-sectional16456.759.8%HCV 54.88%, alcohol 38.41%, others 6.7%NAA 52.44%B/C 47.56%164EV72.6%NANA1.3 /NA8Pai (2012)IndiaProspective (abstract)114NANANANANA114EVNA48.2%NANA /150.568Wang (2012)ChinaProspective12654.5±10.173.8%HBV 100%0.0%A 100%126EV38.1%10.3%Small varices of red color, and medium or large varices.0.77 /1.2410Reed (2011)EnglandNA (abstract)96NANAHCV 28.1%, alcohol 27.1%, cryptogenic or others 44.8%NANA96EV26.0%13.5%NANA /NA8Stefanescu (2011)RomaniaCross-sectional23155.66±9.51958.4%HCV 49.78%, alcohol 38.96%, viral+alcohol 11.26%NAA 75.9%B 18.4%C 5.7%231EV68.0%29.5%Enlarged, tortuous EV occupying <1/3 of the lumen; large, coil-shaped EV occupying >1/3 of the lumen.1.434 /2.20110Tafarel (2011)BrazilProspective30053.1±12.1564.3%Viral 49%, alcohol 24%, viral+alcohol 5.33%, cryptogenic or others 21.67%0.0%A 70.7%B 24.3%C 5%300EV57.0%3.3%Varices did not disappear with air insufflation and occupied >1/3 of the esophageal lumen.1.64 /NA10Sebastiani (2010)ItalyRetrospective51059.5±1158.0%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%510EV56.9%19.0%Non-confluent EV protruding in the lumen despite insufflation; confluent thick EV, gastroesophageal junction varices and isolated GVs.1.4 /1.512Castéra (2009)FranceProspective7054.1±11.860.0%HCV 100%NAA 100%70EV35.7%18.6%NA1.3 /1.39Abbreviations: 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.ItemSalzl Calvaruso Zambam de MattosMorishita WangTafarelStefanescuSebastianiCastéraPaiReed Feng1Was the spectrum of patients representative of the patients who will receive the test in practice?YNUNNNNYNUYY2Were selection criteria clearly described?YYNYYYYYYNUY3Is the reference standard likely to correctly classify the target condition?YYYYYYYYYYYY4Is 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)UYNUUYUYUYUU5Did the whole sample or a random selection of the sample, receive verification using a reference standard of diagnosis?YYYYYYYYYYYY6Did patients receive the same reference standard regardless of the index test result?YYYYYYYYYYYY7Was the reference standard independent of the index test (i.e. the index test did not form part of the reference standard)?YYYYYYYYYYYY8Was the execution of the index test described in sufficient detail to permit replication of the test?YNYYYNYYYNNY9Was the execution of the reference standard described in sufficient detail to permit its replication?NYNYYYYYNNNY10Were the index test results interpreted without knowledge of the results of the reference standard?UUUUUUUUUUUU11Were the reference standard results interpreted without knowledge of the results of the index test?UUUUUUUUUUUU12Were the same clinical data available when test results were interpreted as would be available when the test is used in practice?YYYYYYYYYYYY13Were uninterpretable/ intermediate test results reported?UYYYYYYYYYYY14Were withdrawals from the study explained?NYYYYYYYYYYY　Score8108101010101298811Supplementary Table 3. An overview of studies regarding AAR for prediction of varices in liver cirrhosis.First author(Year)RegionsStudy descriptionNo. total PtsAge (year)Male (%)Etiology of cirrhosis HCC (%)Child-Pugh class (%)No. Pts who underwent endoscopyLocation of varicesPrevalence of varices (%)Prevalence of large varices (%)Definitions of large varicesCut-off of varices/large varicesQUADAS ScoreCalvaruso(2013)ItalyProspective9663.2±9.569.8%HCV 100%0.0%A 100%96EV56.3%27.1%>30% of the lumen was occupied.0.8/ 110Reed(2011)EnglandNA (abstract)96NANAHCV 28.1%, alcohol 27.1%, cryptogenic or others 44.8%NANA96EV26.0%13.5%NANA8Sebastiani(2010)ItalyRetrospective51059.5±1158.0%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%510EV56.9%19.0%Non-confluent EV protruding in the lumen despite insufflation; confluent thick EV, gastroesophageal junction varices and isolated GVs.1/ 1.112Castéra(2009)FranceProspective7054.1±11.860.0%HCV 100%NAA 100%70EV35.7%18.6%NA1/ 19Abbreviations: 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.ItemCalvaruso SebastianiCastéraReed 1Was the spectrum of patients representative of the patients who will receive the test in practice?NYNY2Were selection criteria clearly described?YYYU3Is the reference standard likely to correctly classify the target condition?YYYY4Is 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)YYUU5Did the whole sample or a random selection of the sample, receive verification using a reference standard of diagnosis?YYYY6Did patients receive the same reference standard regardless of the index test result?YYYY7Was the reference standard independent of the index test (i.e. the index test did not form part of the reference standard)?YYYY8Was the execution of the index test described in sufficient detail to permit replication of the test?NYYN9Was the execution of the reference standard described in sufficient detail to permit its replication?YYNN10Were the index test results interpreted without knowledge of the results of the reference standard?UUUU11Were the reference standard results interpreted without knowledge of the results of the index test?UUUU12Were the same clinical data available when test results were interpreted as would be available when the test is used in practice?YYYY13Were uninterpretable/ intermediate test results reported?YYYY14Were withdrawals from the study explained?YYYY　Score101298Supplementary Table 5. Study characteristics: An overview of studies regarding FIB-4 for prediction of varices in liver cirrhosis.First author(Year)RegionsStudy descriptionNo. total PtsAge (year)Male (%)Etiology of cirrhosisHCC (%)Child-Pugh class (%)No. Pts who underwent endoscopyLocation of varicesPrevalence of varices (%)Prevalence of large varices (%)Definitions of large varicesCut-off of varices/large varicesQUADAS ScoreMorishita(2014)JapanNA9268.7±9.351.1%HCV 100%50.0%A 65.2 %B 32.6 %C 2.2 %92EV51.1%33.7%Straight small-calibered varices with RC signs; moderately enlarged, beady varices; markedly enlarged, nodular, or tumor-shaped varices.6.21/7.710Reed(2011)EnglandNA (abstract)96NANAHCV 28.1%,alcohol 27.1%, cryptogenic or others 44.8%NANA96EV26.0%13.5%NANA/NA7Stefanescu (2011)RomaniaCross-sectional23155.66±9.51958.4%HCV 49.78%, alcohol 38.96%, viral+alcohol 11.26%NAA 75.9%B 18.4%C 5.7%231EV68.0%29.5%Enlarged, tortuous EV occupying less than one third of the lumen; large, coil-shaped EV occupying more than one third of the lumen.3.98/6.749810Sebastiani (2010)ItalyRetrospective51059.5±1158.0%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%510EV56.9%19.0%Non-confluent EV protruding in the lumen despite insufflation; confluent thick EV, gastroesophageal junction varices and isolated gastric varices.3.5/4.312Hassan (2014)EgyptProspective6552.40 ± 6.1560.0%HCV 100%0.0%A 80.0%B 20.0%65EV76.9%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.2.8/3.310Abbreviations: EV, esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.Supplementary Table 6. Study quality: An overview of studies regarding FIB-4 for prediction of varices in liver cirrhosis.No.ItemMorishita StefanescuSebastianiReed Hassan1Was the spectrum of patients representative of the patients who will receive the test in practice?NNYYN2Were selection criteria clearly described?YYYUY3Is the reference standard likely to correctly classify the target condition?YYYYY4Is 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)UUYUU5Did the whole sample or a random selection of the sample, receive verification using a reference standard of diagnosis?YYYYY6Did patients receive the same reference standard regardless of the index test result?YYYYY7Was the reference standard independent of the index test (i.e. the index test did not form part of the reference standard)?YYYYY8Was the execution of the index test described in sufficient detail to permit replication of the test?YYYNY9Was the execution of the reference standard described in sufficient detail to permit its replication?YYYNY10Were the index test results interpreted without knowledge of the results of the reference standard?UUUUU11Were the reference standard results interpreted without knowledge of the results of the index test?UUUUU12Were the same clinical data available when test results were interpreted as would be available when the test is used in practice?YYYUY13Were uninterpretable/ intermediate test results reported?YYYYY14Were withdrawals from the study explained?YYYYY　Score101012710Supplementary Table 7. Study characteristics: An overview of studies regarding Lok for prediction of varices in liver cirrhosis.First author(Year)RegionsStudy descriptionNo. total PtsAge (year)Male (%)Etiology of cirrhosisHCC (%)Child-Pugh class (%)No. Pts who underwent endoscopyLocation of varicesPrevalence of varices (%)Prevalence of large varices (%)Definitions of large varicesCut-off of varices/large varicesQUADAS ScoreHassan (2014)EgyptProspective6552.40 ± 6.1560.0%HCV 100%0.0%A 80.0%B 20.0%65EV76.9%49.2%Enlarged, tortuous EV occupying <1/3 of the lumen; large, coil-shaped EV occupying >1/3 of the lumen.0.63/0.710Stefanescu (2011)RomaniaCross-sectional23155.66±9.51958.4%HCV 49.78%, alcohol 38.96%, viral+alcohol 11.26%NAA 75.9%B 18.4%C 5.7%231EV68.0%29.5%Enlarged, tortuous EV occupying <1/3 of the lumen; large, coil-shaped EV occupying >1/3 of the lumen.0.62/0.79610Sebastiani (2010)ItalyRetrospective51059.5±1158.0%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%510EV56.9%19.0%Non-confluent EV protruding in the lumen despite insufflation; confluent thick EV, gastroesophageal junction varices and isolated GVs.0.9/1.512Castéra (2009)FranceProspective7054.1±11.860.0%HCV 100%NAA 100%70EV35.7%18.6%NA0.6/0.69Abbreviations: 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.ItemStefanescuSebastianiHassanCastéra1Was the spectrum of patients representative of the patients who will receive the test in practice?NYNN2Were selection criteria clearly described?YYYY3Is the reference standard likely to correctly classify the target condition?YYYY4Is 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)UYUU5Did the whole sample or a random selection of the sample, receive verification using a reference standard of diagnosis?YYYY6Did patients receive the same reference standard regardless of the index test result?YYYY7Was the reference standard independent of the index test (i.e. the index test did not form part of the reference standard)?YYYY8Was the execution of the index test described in sufficient detail to permit replication of the test?YYYY9Was the execution of the reference standard described in sufficient detail to permit its replication?YYYN10Were the index test results interpreted without knowledge of the results of the reference standard?UUUU11Were the reference standard results interpreted without knowledge of the results of the index test?UUUU12Were the same clinical data available when test results were interpreted as would be available when the test is used in practice?YYYY13Were uninterpretable/ intermediate test results reported?YYYY14Were withdrawals from the study explained?YYYY　Score1012109Supplementary Table 9. Study characteristics: An overview of studies regarding Forns score for prediction of varices in liver cirrhosis.First author(Year)RegionsStudy descriptionNo. total PtsAge (year)Male (%)Etiology of cirrhosis HCC (%)Child-Pugh class (%)No. Pts who underwent endoscopyLocation of varicesPrevalence of varices (%)Prevalence of large varices (%)Definitions of large varicesCut-off of varices/large varicesQUADAS ScoreHassan (2014)EgyptProspective6552.40 ± 6.1560.0%HCV 100%0.0%A 80.0%B 20.0%65EV76.9%49.2%Enlarged, tortuous EV occupying <1/3 of the lumen; large, coil-shaped EV occupying >1/3 of the lumen.6.61/6.910Stefanescu (2011)RomaniaCross-sectional23155.66±9.51958.4%HCV 49.78%, alcohol 38.96%, viral+alcohol 11.26%NAA 75.9%B 18.4%C 5.7%231EV68.0%29.5%Enlarged, tortuous EV occupying <1/3 of the lumen; large, coil-shaped EV occupying >1/3 of the lumen.7.297/8.53810Sebastiani (2010)ItalyRetrospective51059.5±1158.0%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%510EV56.9%19.0%Non-confluent EV protruding in the lumen despite insufflation; confluent thick EV, gastroesophageal junction varices and isolated GVs.8.5/8.812Abbreviations: EV, esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.Supplementary Table 10. Study quality: An overview of studies regarding Forns score for prediction of varices in liver cirrhosis.No.ItemStefanescuSebastianiHassan1Was the spectrum of patients representative of the patients who will receive the test in practice?NYN2Were selection criteria clearly described?YYY3Is the reference standard likely to correctly classify the target condition?YYY4Is 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)UYU5Did the whole sample or a random selection of the sample, receive verification using a reference standard of diagnosis?YYY6Did patients receive the same reference standard regardless of the index test result?YYY7Was the reference standard independent of the index test (i.e. the index test did not form part of the reference standard)?YYY8Was the execution of the index test described in sufficient detail to permit replication of the test?YYY9Was the execution of the reference standard described in sufficient detail to permit its replication?YYY10Were the index test results interpreted without knowledge of the results of the reference standard?UUU11Were the reference standard results interpreted without knowledge of the results of the index test?UUU12Were the same clinical data available when test results were interpreted as would be available when the test is used in practice?YYY13Were uninterpretable/intermediate test results reported?YYY14Were withdrawals from the study explained?YYY　Score101210Supplementary Table 11. Study characteristics: An overview of studies regarding FibroIndex for prediction of varices in liver cirrhosis.First author (Year)RegionsStudy descriptionNo. total PtsAge (year)Male (%)Etiology of cirrhosis HCC (%)Child-Pugh class (%)No. Pts who underwent endoscopyLocation of varicesPrevalence of varices (%)Prevalence of large varices (%)Definitions of large varicesCut-off of varices/large varicesQUADAS ScoreSebastiani (2010)ItalyRetrospective51059.5±1158.0%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%510EV56.9%19.0%Non-confluent EV protruding in the lumen despite insufflation; confluent thick EV, gastroesophageal junction varices and isolated GVs.2.2/ 2.512Abbreviations: EV, esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.Supplementary Table 12. Study quality: An overview of studies regarding FibroIndex for prediction of varices in liver cirrhosis.No.ItemSebastiani1Was the spectrum of patients representative of the patients who will receive the test in practice?Y2Were selection criteria clearly described?Y3Is the reference standard likely to correctly classify the target condition?Y4Is 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)Y5Did the whole sample or a random selection of the sample, receive verification using a reference standard of diagnosis?Y6Did patients receive the same reference standard regardless of the index test result?Y7Was the reference standard independent of the index test (i.e. the index test did not form part of the reference standard)?Y8Was the execution of the index test described in sufficient detail to permit replication of the test?Y9Was the execution of the reference standard described in sufficient detail to permit its replication?Y10Were the index test results interpreted without knowledge of the results of the reference standard?U11Were the reference standard results interpreted without knowledge of the results of the index test?U12Were the same clinical data available when test results were interpreted as would be available when the test is used in practice?Y13Were uninterpretable/ intermediate test results reported?Y14Were withdrawals from the study explained?Y　Score12Supplementary 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.Supplementary Figure 7. Flowchart of study inclusion regarding Forns score.Supplementary Figure 8. Flowchart of study inclusion 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. ................
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