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. 2018 Nov 7;17(4):301–315. doi: 10.1007/s11901-018-0420-z

Table 1.

Summary of prospective studies and meta-analyses on the diagnostic value of transient elastography for the diagnosis of any varices and “varices needing treatment”

Author, journal, year Design and etiology N patients overall
N patients with any EV (%)
N patients with VNT (%)
TE-cutoffs and AUC any EV/VNT Main conclusions (specificity/sensitivity, PPV/NPV) Additional parameters used in the study and comments
Foucher, Gut, 2006 [17] Prospective
Mixed etiology
n = 144 patients with F3/F4 fibrosis
n with any EV: n/a
n = 42 (29%)/85 (59%) with VNT
LSM:
Any: n/a
VNT 27.5 kPa, AUC 0.73
LSM:
Any: n/a
VNT: Sens. 88%, Spec. 53%, PPV 45%, NPV 90%
• The main focus was diagnosis of fibrosis stages using TE
Kazemi, J Hepatol, 2006 [18] Prospective
Mixed etiology
N = 165 patients analyzed
n = 74 (44.8%) with EV
n = 47 (28.5%) with VNT
LSM:
Any 13.9 kPa, AUC 0.84
VNT 19.0 kPa, AUC 0.83,
LSM:
Any: Sens. 92%, Spec. 39%, PPV 55%, NPV 85%
VNT Sens. 89%, Spec. 59%, PPV 47%, NPV 93%
Parameters: PLT, spleen diameter, PLT, LSM/spleen size
Vizzutti, Hepatology, 2007 [19] Prospective
Etiology: HCV
n = 61 patients analyzed
n = 30 (49.2%) with esophageal EV
n = 18 (38.2%) with large EV/VNT
LSM:
Any 17.6 kPa, AUC 0.76
VNT 27.4 kPa, AUC 0.76
LSM:
Any Sens. 90%, spec. 43%, PPV 77%, NPV 66%
VNT Sens. 70%, spec. 78%, PPV 90%, NPV 55%
Bureau, Aliment Pharmacol Ther, 2008 [20] Prospective
Mixed etiology
n = 150 patients analyzed
n = 64 (42.6%) with EV
n = 43 (28.6%) with VNT
LSM:
Any 21.1 kPa, AUC 0.85
VNT/large 29.3 kPa
AUC 0.76
LSM:
Any Sens. 84%, Spec. 71%
VNT Sens. 81%, Spec. 61%
Parameters: Prothrombin index
VNT: large EV
Castéra, J Hepatol, 2009 [21] Prospective
Etiology: HCV
n = 70 patients with cirrhosis analyzed
n = 25 with EV
n = 13 with VNT
LSM:
* Any
13.9 kPa (Kazemi 2006)
17.6 kPa (Vizutti 2007)
21.5 kPa, AUC 0.96
* VNT
19 kPa (Kazemi 2006)
21.5 kPa, AUC 0.87
30 kPa, AUC 0.87
LSM:
*Any:
Cutoff 13.9 kPa: Sens. 96%, Spec. 39%, PPV 49%, NPV 94%
Cutoff 17.6 kPa: Sens. 84%, Spec. 61%, PPV 57%, NPV 86%
Cutoff 21.5 kPa: Sens. 76%, Spec. 78%, PPV 68%, NPV 84%
*VNT:
Cutoff 19.0 kPa: Sens. 85%, Spec. 62%, PPV 35%, NPV 94%
Cutoff 21.5 kPa: Sens. 85%, Spec. 68%, PPV 39%, NPV 95%
Cutoff 30.5 kPa: Sens. 77%, Spec. 5%, PPV 56%, NPV 94%10
Parameters: PLT, FibroTest, prothrombin index, AST/ALT ratio, APRI, Lok index
Kim, Am J Gastroenterol, 2010 [22] Prospective
Etiology: HBV
n = 391
n = 184 (47%) with EV
n = 133 (34%) with VNT
LSM: n/a
LSPS:
Any: n/a
VNT 3.5, AUC 0.95
LSM: n/a
LSPS:
VNT: Cutoff 3.5: Sens. 88%, Spec. 91%, PPV 82%, NPV 94%
VNT: Cutoff 5.5: Sens. 72%, Spec. 98% PPV 94%, NPV 88%
• Diagnostic accuracy varies with severity of cirrhosis: LPS: AUC 0.94 (Child-Pugh A), AUC 0.88 (Child-Pugh B/C).
• Included cirrhosis Child-Pugh A-C, training cohort and validation cohort
Nguyen-Khac, Alcohol Clin Exp Res, 2010 [23] Prospective
Mixed etiologies
n = 183 patients analyzed
n = 41 (22%) with large EV/VNT
LSM:
VNT 48 kPa; AUC 0.75
VNT (ALD) 47.2 kPa, AUC 0.77
VNT (viral) 19.8 kPa, AUC 0.73
LSM:
VNT: Sens. 73%, Spec. 73%, PPV 44%, NPV 90%
VNT (ALD): Sens. 85%, Spec. 64%, PPV 44%, NPV 93%
VNT (viral): Sens. 89%, Spec. 55%, PPV 27%, NPV 96%
Stefanescu, J Gastroenterol Hepatol, 2011 [24] Prospective
Etiology: ALD and/or HCV or healthy controls
n = 137 with cirrhosis analyzed
n = 116 (85%) with EV
n = 60 (44%) with VNT
LSM:
Any 28 kPa, AUC 0.75
SSM:
Any 46.4 kPa, AUC 0.78
LSM + SSM:
Any: LSM 19 kPa, SSM 55 kPa
LSM:
Any: Sens. 74%, Spec. 64%, PPV 92%, NPV 31%
SSM:
Any: Sens. 84%, Spec. 71%, PPV 94%, NPV 46%
LSM (19 kPa) + SSM (55 kPa):
Any: Sens. 93%, Spec. 40%, PPV 95%, NPV 33%
Parameters: PLT/spleen size ratio; LSM × SSM
VNT: cutoffs n/a
Stefanescu, J Gastrointest Liver Dis, 2011 [25] Prospective
Etiology: ALD and/or HCV
n = 231 patients analyzed
n = 157 (68%) with EV
n = 68 (30%) with VNT
LSM:
Any 19 kPa, AUC 0.66
VNT 38 kPa, AUC 0.69
LSM:
Any: Sens. 84%, Spec. 32%, PPV 72%, NPV 49%
VNT: Sens. 56%, Spec. 75%, PPV 47%, NPV 81%
Included cirrhosis
Excluded decompensated cirrhosis, co-infection with viral hepatitis
Parameters: APRI, Forns Index, Lok Score, FIB4
VNT: grades 2–3 EV
Chen, J Gastroenterol Hepatol, 2012 [26] Prospective
Etiology: HBV
n = 222 patients analyzed
n = 96 (43%) with EV
n = 82 (40%) with VNT
LSM:
VNT 17.1 kPa, AUC 0.73 (all)
VNT 36.1 kPa, AUC 0.92 (ALT > 5 × ULN)
VNT 7.9 kPa, AUC 0.79 (Child-Pugh A, rule out EV)
VNT 34.6 kPa (Child-Pugh A, rule in EV)
LSPS:
VNT Cutoff 3.5, cutoff 5.5; AUC 0.81
LSM:
VNT: Cutoff 17.1 kPa: Sens. 90%, Spec. 44%, PPV 47%, NPV 88%
VNT: Cutoff 36.1 kPa: PPV 73%, NPV 100%
VNT: Cutoff 7.9 kPa: Sens. 97%, NPV 95%
VNT: Cutoff 34.6 kPa: Spec. 94%, PPV 73%
LSPS:
VNT: Cutoff 3.5: Sens. 78%, NPV 86% (exclusion)
VNT: Cutoff 5.5: Spec. 90%, PPV 76% (inclusion)
Included cirrhosis
Excluded history of variceal bleeding, NSBB therapy, TIPS
VNT: medium or large EV, or small with RSS, or decompensated cirrhosis
Parameters: USLS; LSM × ALT, LSM × Child-Pugh, LSPS, age-PLT-AST/ALT ratio, PLT/spleen diameter ratio
Wang, J Gastroenterol Hepatol, 2012 [27] Prospective
Etiology: HBV
n = 126 patients analyzed
n = 48 (38%) with EV
n = 13 (10%) with VNT
LSM:
Any 12.0 kPa, AUC 0.79
VNT 21.0 kPa, AUC 0.87
LSM:
Any: Sens. 67%, Spec. 77%, PPV 64%, NPV 79%
VNT: Sens. 77%, Spec. 87%, PPV 40%, NPV 97%
Parameters:
APRI, PLT, AST/ALT ratio
Colecchia, Gastroenterology, 2012 [28] Prospective
Etiology: HCV
n = 100 patients analyzed
n = 53 (53%)with EV
n = 26 (26%) with VNT
LSM (AUC 0.90):
Any: cutoff 16.4 kPa
Any: cutoff 25.0 kPa
SSM (AUC 0.94):
Any: cutoff 41.3 kPa
Any: cutoff 55.0 kPa
LSPS (AUC 0.91)
Any: cutoff 1.32
Any: cutoff 3.83
LSM:
Any: cutoff 16.4 kPa; Sens. 96%, Spec. 60% (rule out)
Any: cutoff 25.0 kPa, Sens. 57%, Spec. 98% (rule in)
SSM:
Any: cutoff 41.3 kPa, Sens. 98%, Spec. 66% (rule out)
Any: cutoff 55.0 kPa, Sens. 72%, Spec. 96% (rule in)
LSPS:
Any: cutoff 1.32: Sens. 98%, Spec. 64% (rule out)
Any: cutoff 3.83: Sens. 60%, Spec. 98% (rule in)
• LSM and SSM for detection of HVPG > 12 mmHg and EV
• Parameters:
• LSPS, PLT/spleen size
Calvaruso,
J Viral Hepat, 2013 [29]
Prospective
Etiology: HCV
n = 96 patients analyzed
n = 54 (56.3%) with EV
n = 26 (27.1%) with VNT
LSM:
Any 17.0 kPa, AUC 0.71
VNT 19.0 kPa, AUC 0.71
Modified SSM (0-150 kPa):
Any 50.0 kPa, AUC 0.70
VNT 54.0 kPa, AUC 0.82
LSM:
Any: Sens. 71%, Spec. 57%, PPV 67%, NPV 62%
VNT: Sens. 72% Spec. 55%, PPV 38%, NPV 84%
Modified SSM:
Any: Sens. 65%, Spec. 61%, PPV 69%, NPV 57%
VNT: Sens. 80%, Spec. 70%, PPV 47%, NPV 90%
• Modified SSM: values 0–150 kPa
• Parameters: Gender, age, AST, ALT, PLT, AST/ALT ratio, APRI, spleen diameter
Shi, Liver Int, 2013 [30] Meta-analysis
All etiologies, with sub-analyses for viral etiology (HCV + HBV)
n = 3644 patients analyzed
n = 1786? (49.0%) with EV
n = 1166? (32.0%) with VNT
LSM (pooled):
Any: Cutoffs 15.1–28.0 kPa; AUC 0.84
VNT: Cutoffs: 17.8–48.0 kPa; AUC 0.78
LSM (pooled):
Any: Cutoffs 15.1–28.0 kPa: Sens. 87%, Spec. 53%, PPV 79%, NPV 64%
VNT: Cutoffs: 17.8–48.0 kPa: Sens. 86%, Spec. 59%,, PPV 79%, NPV 66%
Sharma, Am J Gastroenterol, 2013 [31] Prospective
Mixed etiologies
n = 174 patients analyzed
n = 124 patients with EV
n = 78 with large EV/VNT
LSM:
Any 27.3 kPa, AUC 0.91
VNT: n/a
SSM:
Any 40.8 kPa, AUC 0.90
LSPS:
Any 3.09, AUC 0.87
LSM:
Any: Sens. 91%, Spec. 72%, PPV 89%, NPV 76%
SSM:
Any: Sens. 94%, Spec. 76%, PPV 91%, NPV 84%
LSPS:
Any: Sens. 89%, Spec. 76%, PPV and NPV not reported
• Only LS und SS independently associated with presence of EV;
• SSM: can differentiate between large and small EV
• LSM: Cannot differentiate between large and small EV
• Included cirrhosis
• Excluded decompensated cirrhosis, ACLF, active alcohol abuse
• Parameters: LSPS, PLT/spleen diameter ratio
Binţinţan, Med Ultrason, 2015 [32] Prospective
Etiology: viral and/or ALD
n = 60 patients with cirrhosis
n = 47 (78%) with EV
n = 32 (53%) with VNT
LSM:
Any 15 kPa, AUC 0.96
VNT 28.8 kPa, AUC 0.90
LSM:
Any: Sens. 95%, Spec. 100%, PPV 100%, NPV 86%
VNT: Sens. 87%, Spec. 83%, PPV 84%, NPV 86%
Parameters: hemodynamic liver index, portal vascular resistance, spleno-portal index
Hu, Ultrasound Med Biol, 2015 [33] Prospective
Etiology: viral (HBV, HCV)
n = 200 patients analyzed
n = 110 (55%) with EV
n = 69 (35%) with large EV
LSM:
Any 20.3 kPa, AUC 0.84
VNT 25.6 kPa, AUC 0.86
LSM:
Any: Sens. 84%, Spec. 73%, PPV 72%, NPV 91%
VNT: Sens. 86%, Spec. 72%, PPV 79%, NPV 81%
VNT: grade 2 or 3 EV
Parameters: LSM x PLT (no detailed description available)
Marot, Liver Int, 2017 [34] Meta-analysis
Mixed etiologies
n = 3364
n = (49.0%) with EV
n = (32.0%) with VNT
LSM:
Any 20 kPa*
LSM and PLT (150 G/L):
VNT 20 kPa × PLT 150 G/L*
LSM and PLT (150 G/L):
Any: Sens. 89%, Spec. 38%, PPV 43%, NPV 86%
VNT: Sens. 93%, Spec. 30%, PPV 14%, NPV 97%
• Focus on risk of bleeding rather than finding cutoffs for prediction of EV
• VNT: variable definition between studies
Pu, J Gastroenterol, 2017 [35] Meta-analysis
Mixed etiologies
n = 2697 patients analyzed
Patients with EV: n/a
LSM (pooled):
Any 20 kPa, AUC 0.83
VNT 30 kPa, AUC 0.83
LSM:
Any (pooled): Sens. 84%, Spec. 62%,
Any: Cutoff 20 kPa: Sens. 83%, Spec. 68%, PPV: n/a, NPV: n/a
VNT (pooled): Sens. 78%, Spec. 76%,
VNT: Cutoff 30 kPa: Sens. 73%, Spec. 74%, PPV: n/a, NPV: n/a
VNT: large EV
Llop, J Gastroenterol Hepatol, 2017 [36] Retrospective analysis of prospective data
Mixed etiology
n = 161 patients analyzed
n = 25 (15.5%) with EV
VNT: n/a
LSM
Any 20.0 kPa*
LSM + PLT:*
Any 20.0 kPa x PLT 150 G/L*
LSPS:
Any: cutoff 3.21;
LSM:
Any: Cutoff 20 kPa*: Sens. 76%, Spec. 71%, PPV 32%, NPV 94%
LSM and PLT (150 G/L)*:
Any: Cutoff 20 kPa*: Sens. 88%, Spec. 38%, PPV 21%, NPV 94%
LSPS:
Any: Sens. 36%, Spec. 84%, PPV 30%, NPV 88%
TE is the best single method to predict EV; LSPS had high and Baveno VI criteria low risk of misclassifying patients with EV
Included LSM >10 kPa
Excluded decompensated cirrhosis
Parameters: PLT, spleen diameter, LSPS, variceal risk index
Augustin algorithm, Baveno VI
AUC was calculated but not reported
Wong, Liver Int, 2018 [37] Prospective LSM: Total n = 274/548
n = 51 (18.6%) with EV
n = 11 (4.0%) with VNT
LSM:
Any 12.5 kPa*
VNT 20.0 kPa × PLT 150 G/L*
SSM:
VNT 41.3 kPa
LSM:
Any: Cutoff 20 kPa*: Sens 96%, Spec. 91%, PPV 26%, NPV 47%
VNT: Cutoff 12.5 kPa: Sens. 98%, NPV: 94%
VNT: Cutoff 20 kPa*: Sens. 91%, Spec. 18.1%, PPV 10%, NPV 96%
SSM:
Any 98%, NPV 94%
LSM (12.5 kPa) × SSM (41.3 kPa)
Manatsathit, J Gastroenterol Hepatol, 2018 [38] Meta-analysis
Mixed etiologies
Any EV:
n = 1681/3001 (56% of LSM) and n = 968/1911 (51% of SSM) with EV
VNT:
n = 1466/4337 (34% of LSM) and n = 383/1119 (34% of SSM) with VNT
LSM (pooled):
Any: AUC 0.82
VNT: AUC 0.83
SSM (pooled):
Any: AUC 0.90
VNT: AUC 0.81
LSPS (pooled):
Any: AUC 0.85
VNT: AUC 0.86
LSM (pooled):
Sens. 84%, Spec. 64%
Any: Sens. 85%, Spec. 64%
VNT: Sens. 85%, Spec. 63%
SSM (pooled):
Sens. 91% Spec. 66%
Any: Sens. 90%, Spec. 73%
VNT: Sens. 87%, Spec. 52%
LSPS (pooled):
Any: Sens. 91%, Spec. 67%
VNT: Sens. 82%, Spec. 87%
Sub-analyses regarding method (TE, ARFI, others), etiology (ALD vs viral), ethnicity (Asian vs Western), and cACLD vs decompensated cirrhosis
No cutoffs calculated!

ALD, alcoholic liver disease; ACLF, acute on chronic liver failure; APRI, AST to PLT ratio index; ARFI, acoustic radiation force impulse; AUC, area under the (receiver operating) curve; cACLD, compensated advanced chronic liver disease; EV, esophageal varices; F, fibrosis stage; FIB4, fibrosis 4 (score); kPa, kilopascal (unit); LS(M), liver stiffness (measurement); LSPS, liver-stiffness-to-spleen-diameter-to-platelet-ratio score; NPV, negative predictive value; PLT, platelet count; PPV, positive predictive value; RSS, red spot sign; SS(M), spleen stiffness (measurement); TE, transient elastography; TIPS, transjugular intrahepatic portosystemic shunt; ULN, upper limit of normal; USLS, ultrasound and liver stiffness score; VNT, varices in need of treatment

The asterisk * refers to validation data for the cutoff recommend by the Baveno VI consensus conference