Elastography-based screening for esophageal varices in patients with advanced chronic liver disease

Table 1 Studies on transient elastography for the prediction of varices

Author, journal, year of publication	Country	Study design	Etiology	N Patients included % with EV % with VNT		TE-Cut-offs and AUC EV/VNT	Main conclusions (Specificity/Sensitivity, PPV/NPV)
Foucher, Gut, 2006[16]	France	Prospective	Mixed	EV: VNT:	144 42 (29%) 85 (59%)	LSM: n/a 27.5 kPa, AUC 0.73	LSM: EV: n/a VNT: Sens. 88%, Spec. 53%, PPV: 45%, NPV: 90%
Kazemi, J Hepatol, 2006[15]	France	Prospective	Mixed	EV: VNT	Total: 165 74 (44.8%) 47 (28.5%)	LSM: 13.9 kPa, AUC: 0.84 19.0 kPa, AUC 0.83,	LSM: EV: Sens. 92%, Spec. 39%, PPV 55%, NPV 85% VNT: Sens. 89%, Spec. 59%, PPV 47%, NPV: 93%
Vizzutti, Hepatology, 2007[80]	Italy	Prospective	HCV	EV: VNT	Total: 61 30 (49.2%) 18 (38.2%)	LSM: 17.6 kPa, AUC 0.76 27.4 kPa, AUC 0.76	LSM: EV: Sens. 90%, spec. 43%, PPV 77%, NPV 66% VNT: Sens. 70%, spec. 78%, PPV 90%, NPV 55%
Bureau, Aliment Pharmacol Ther, 2008[81]	France	Prospective	Mixed	EV: VNT	Total: 150 64 (42.6%) 43 (28.6%)	LSM: EV: 21.1 kPa, AUC 0.85 VNT/large: 29.3 kPa, AUC 0.76	LSM: EV: sens. 84%, spec. 71% VNT: sens. 81%, spec. 61%
Castéra, J Hepatol, 2009[82]	France	Prospective	HCV	EV: VNT	Total: 70 25 (35.7%) 15 (21.4%)	LSM: 13.9 kPa, 17.6 kPa, 21.5 kP; AUC 0.96 19 kPa, 21.5 kPa; 30 kPa, AUC 0.87	LSM: Cut-off 13.9 kPa: Sens. 96%, Spec. 39%, PPV 49%, NPV 94% Cut-off 17.6 kPa: Sens. 84%, Spec. 61%, PPV 57%, NPV 86% Cut-off 21.5 kPa: Sens. 76%, Spec. 78%, PPV 68%, NPV 84% Cut-off 19.0 kPa: Sens. 85%, Spec. 62%, PPV 35%, NPV 94% Cut-off 21.5 kPa: Sens. 85%, Spec. 68%, PPV 39%, NPV 95% Cut-off 30.5 kPa: Sens. 77%, Spec. 5%, PPV 56%, NPV 94%10
Nguyen-Khac, Alcohol Clin Exp Res; 2010[20]	France	Prospective	Mixed	EV: VNT	Total: 183 NR 41 (22%)	LSM: 48 kPa; AUC 0.75 ALD: 47.2 kPa, AUC 0.77 Viral: 19.8 kPa, AUC 0.73	LSM: Sens. 73%, Spec. 73%, PPV 44%, NPV 90% ALD: Sens. 85%, Spec. 64%, PPV 44%, NPV 93% Viral: Sens. 89%, Spec. 55%, PPV 27%, NPV 96%
Stefanescu, J Gastroenterol Hepatol, 2011[18]	Romania	Prospective	ALD and/or HCV or healthy controls	EV: VNT	Total: 137 116 (85%) 60 (44%)	LSM: EV: 28 kPa, AUC 0.75 SSM: EV: 46.4 kPa, AUC 0.78 LSM + SSM: EV: LSM 19 kPa, SSM 55 kPa NR	LSM: Sens. 74%, Spec. 64%, PPV 92%, NPV 31% SSM: Sens. 84%, Spec. 71%, PPV 94%, NPV 46% LSM (19 kPa) + SSM (55 kPa): Sens. 93%, Spec. 40%, PPV 95%, NPV 33% NR
Stefanescu, J Gastrointestin Liver Dis, 2011[83]	Romania	Prospective	ALD and/or HCV	EV: VNT	Total: 231 157 (68%) 68 (30%)	LSM: 19 kPa, AUC 0.66 38 kPa, AUC 0.69	LSM: Sens. 84%, Spec. 32%, PPV 72%, NPV 49% Sens. 56%, Spec. 75%, PPV 47%, NPV 81%
Chen, J Gastroenterol Hepatol, 2012[84]	China	Prospective	HBV	EV: VNT	Total: 222 96 (43%) 82 (40%)	LSM: NR All 17.1 kPa, AUC 0.73 ALT >5 x ULN: 36.1 kPa, AUC 0.92 CPC A, rule-out EV : 7.9 kPa, AUC 0.79 CPC A, rule-in 34.6 kPa, AUC 0.79	LSM: NR Cut-off 17.1 kPa: Sens. 90%, Spec. 44%, PPV 47%, NPV: 88% Cut-off 36.1 kPa: PPV 73%, NPV 100% Cut-off 7.9 kPa: Sens. 97%, NPV 95% Cut-off 34.6 kPa: Spec. 94%, PPV 73% LSPS: Cut-off 3.5: Sens. 78%, NPV 86% (exclusion) Cut-off 5.5: Spec. 90%, PPV 76% (inclusion)
Wang, J Gastroenterol Hepatol, 2012[85]	Taiwan	Prospective	HBV	EV: VNT	Total: 126 48 (38%) 13 (10%)	LSM: 12.0 kPa, AUC 0.79 21.0 kPa, AUC 0.87	LSM: Sens. 67%, Spec. 77%, PPV 64%, NPV 79% Sens. 77%, Spec. 87%, PPV 40%, NPV 97%
Colecchia, Gastroenterology, 2012[32]	Italy	Prospective	HCV	EV: VNT:	Total: 100 53 (53%) 26 (26%)	LSM (AUC 0.90): cut-off 16.4 kPa cut-off 25.0 kPa SSM (AUC 0.94): cut-off 41.3 kPa cut-off 55.0 kPa NR	LSM: Sens. 96%, Spec. 60% (rule out) Sens. 57%, Spec. 98% (rule in) SSM: Sens. 98%, Spec. 66% (rule out) Sens. 72%, Spec. 96% (rule in) NR
Sporea, Med Ultrason, 2013[86]	Romania	Prospective	Viralalcoholic	EV: VNT:	Total: 697 387 (54.5%) 273 (39.1%)	NR All: 29.5 kPa (0.871) Alcohol: 32.5 kPa (0.836) Viral: 24.8 kPa (0.867)	NR Sens. 77.5%, Spec. 86.9% Sens. 85.0%, Spec. 74.6% Sens. 81.0%, Spec. 80.7%
Calvaruso, J Viral Hepat, 2013[33]	Italy	Prospective	HCV	EV: VNT:	Total: 96 54 (56.3%) 26 (27.1%)	LSM:17.0 kPa, AUC 0.71 Modified SSM (0-150kPa): 50.0kPa, AUC 0.70 LSM: 19.0 kPa, AUC 0.71 Modified SSM (0-150kPa): 54.0 kPa, AUC 0.82	LSM: Sens. 71%, Spec. 57%, PPV 67%, NPV 62% Modified SSM: Sens. 65%, Spec. 61%, PPV: 69%, NPV: 57% LSM: Sens. 72% Spec. 55%, PPV 38%, NPV 84% Modified SSM: Sens. 80%, Spec. 70%, PPV: 47%, NPV: 90%
Shi, Liver Int, 2013[87]	China	Meta-analysis	Mixed Sub-analyses for viral etiologies	EV: VNT:	Total: 3644 1786 (49.0%) 1166 (32.0%)	LSM (pooled): 15.1-28.0 kPa; AUC 0.84 17.8-48.0 kPa; AUC 0.78	LSM (pooled): Sens. 87%, Spec. 53%, PPV 79%, NPV 64% Sens. 86%, Spec. 59%,, PPV 79%, NPV 66%
Sharma, Am J Gastroenterol, 2013[30]	India	Prospective	Mixed	EV: VNT:	Total: 174 124 (71.3%) 78 (44.8%)	LSM: 27.3 kPa, AUC 0.91; SSM: 40.8 kPa, AUC 0.90 NR	LSM: Sens. 91%, Spec. 72%, PPV 89%, NPV 76%, SSM: Sens. 94%, Spec. 76%, PPV 91%, NPV 84%
Hassan, Gastroenterol Hepatol, 2014[88]	Egypt	Prospective	HCV	EV: VNT:	Total: 62 50 (81%) 32 (52%)	LSM: 18.2 kPa, AUC 0.79 22.4 kPa, AUC 0.80	LSM: Sens. 82%, Spec. 73%, PPV 89%, NPV 49% Sens. 84%, Spec. 72%, PPV 84%, NPV 72%
Binţinţan, Med Ultrason, 2015[21]	Romania	Prospective	ViralALD	EV: VNT:	Total: 60 47 (78%) 32 (53%)	LSM: 15 kPa, AUC 0.96 28.8 kPa, AUC 0.90	LSM: Sens. 95%, Spec. 100%, PPV 100%, NPV 86% Sens. 87%, Spec. 83%, PPV: 84%, NPV: 86%
Hu, Ultrasound Med Biol, 2015[89]	China	Prospective	Viral	EV: VNT:	Total: 200 110 (55%) 69 (35%)	LSM: 20.3 kPa, AUC 0.84 25.6 kPa, AUC 0.86	LSM: Sens. 84%, Spec. 73%, PPV 72%, NPV: 91% Sens. 86%, Spec. 72%, PPV 79%, NPV: 81%
Li et al. Rev Esp Enferm Dig 2016[90]	International	Meta-analysis	Mixed	EV: VNT:	Total: 2,994 Studies: 20 NR NR	LSM NR 14.5-48.0 kPa (0.83)	LSM Sens 81%, Spec 71%,
Wong, J Dig Dis, 2016[17]	Hong Kong	Prospective	Chronic HBV	EV: VNT:	Total: 144 31 (21.5%) 2 (1.4%)	LSM: (0.690) Rule out: 6.8 kPa Rule in: 20.8 kPa SSM: (0.736) Rule out: 21.4 kPa Rule in: 50.5 kPa NR	Sens. 90.3%, Spec 29.2%, PPV 25.9%, NPV 91.7% Sens. 29.0%, Spec. 90.3%, PPV 45.0%, NPV 82.3% Sens. 90.3%, Spec 43.4%, PPV 30.4%, NPV 94.2% Sens. 45.2%, Spec. 90.3%, PPV 56.0%, NPV 85.7% NR
Maurice, J Hepatol, 2016 [22]	United Kingdom	Retrospective	Mixed	EV: VNT:	Total: 310 72 (23%) 15 (5%)	LSM: 20 kPa, AUC 0.686 LSM (20 kPa) and PLT (150 G/L): AUC 0.746	Sens. 67%, Spec. 55%, PPV 7%, NPV 97% Sens. 87%, Spec. 34%, PPV 6%, NPV 98%
Abraldes, Hepatology, 2016 [19]	International	Retrospective	Mixed	EV: VNT:	Total: 518 217 (42%) 67 (13%)	NR (AUC 0.71) LSM: 14.0 kPa (AUC 0.67) LSM (20 kPa) and PLT (150 G/L): AUC 0.76	NR NR NR
Marot, Liver Int, 2017[25]	International	Meta-analysis	Mixed	EV: VNT	Total: 3364 NR (49.0%) NR (32.0%)	LSM: 20 kPa: AUC: NR LSM (20 kPa) and PLT (150 G/L): AUC: NR	LSM and PLT (150 G/L): Sens. 89%, Spec. 38%, PPV: 43%, NPV: 86% Sens. 93%, Spec. 30%, PPV 14%, NPV 97%
Pu, World J Gastroenterol, 2017[26]	International	Meta-analysis	Mixed	EV: VNT:	Total: 2697 NR NR	LSM (pooled): 20 kPa, AUC 0.83 30 kPa, AUC: 0.83	LSM: Pooled: Sens. 84%, Spec. 62%, Cut-off 20 kPa: Sens. 83%, Spec. 68%, PPV: n/a, NPV: n/a Pooled: Sens. 78%, Spec. 76%, Cut-off 30 kPa: Sens. 73%, Spec. 74%, PPV: n/a, NPV: n/a
Llop, J Gastroenterol Hepatol, 2017[23]	Spain	Retrospective analysis of prospective data	Mixed	EV: VNT:	Total: 161 25 (15.5%) NR	LSM: 20.0 kPa, AUC: NR LSM (20 kPa) and Plt (150 G/L), AUC: NR	LSM: Sens. 76%, Spec. 71%, PPV: 32%, NPV: 94% LSM+Plt: Sens. 88%, Spec. 38%, PPV 21%, NPV 94%
Wong, Liver Int, 2018[27]	Hong Kong	Prospective	Mixed	EV: VNT:	TE exam.: 264 51 (18.6%) 11 (4.0%)	LSM:20.0 kPa, AUC: NR LSM (20 kPa) and Plt (150 G/L): AUC: NR SSM: 41.3 kPa; AUC: NR	LSM: Sens: 96%, Spec.: 26%, PPV: 47%, NPV: 91% LSM+PLT: Sens. 91%, Spec.: 18.1%, PPV: 10%, NPV: 96% NR
Manatsathit, J Gastroenterol Hepatol, 2018[31]	USA	Meta-analysis	Mixed	EV: VNT:	LSM: 4,337 SSM: 1,1119 LSM: 1681 (56%) SSM: 968 (51%) LSM: 1466 (34%) SSM: 383 (34%)	LSM (pooled): cut-offs NR; AUC 0.82 SSM (pooled): cut-offs NR; AUC: 0.90 LSM (pooled): cut-offs NR; AUC 0.83 SSM (pooled): cut-offs NR; AUC 0.81	LSM (pooled): Sens. 84%, Spec. 64% SSM (pooled): Sens. 91% Spec. 66% LSM: Sens. 85%, Spec. 64% SSM: Sens. 90%, Spec. 73% LSM: Sens. 85%, Spec. 63% SSM: Sens. 87%, Spec. 52%
Petta, J Hepatol, 2018[28]	Italy	Retrospective analysis of prospective data	NAFLD/NASH	EV: VNT:	Total: 790 249 (31.5%) 91 (11.5%)	NR LSM: 20 kPa + Plt 150 G/L: AUC LSM 25 kPa + Plt 110 G/L: AUC LSM 30 kPa + Plt 110 G&L:	NR Validation set: Sens. 37%, spec. 96%, PPV:18%, NPV:0.96 XL probe, Validation set: Sens. 93%, spec. 51%, PPV: 18%, NPV:98% M probe, validation set: Sens. 78%, spec. 68%, PPV:27%, NPV:96%
Colecchia, J Hepatol, 2018[34]	Italy	Prospective + retrospective validation cohort	Mixed	EV: VNT:	Total: 498 252 (50.6%) 100 (20.1%)	NR LSM: AUC: 0.768 LSM (20 kPa) + Plt (150 G/L): AUC 0.732 SSM: 46 kPa: AUC 0.847 LSM (20 kPa)+Plt (150 G/L)+SSM (46 kPa):AUC 0.787	NR NR Sens. 98%, Spec. 26%, NPV 98% Sens. 98%, Spec. 44%, NPV 99% Sens. 96%, Spec. 53%, NPV 98%

AUC: Area under the (receiver operating) curve; CSPH: Clinically significant portal hypertension; LSM: Liver stiffness measurement; L-SWE: Liver shear wave elastography esophageal varices; TE: Transient elastography; Plt: Platelet count; VNT: Varices needing treatment; Se: Sensitivity; SSM: Spleen stiffness measurement; Sp: Specificity; +LR: Positive likelihood ratio; -LR: Negative likelihood ratio; NR: Not reported; S-SWE: Spleen share wave elastography; ASPS: ARFI-spleen diameter to platelet ratio; ARFI: Acoustic radiation force impulse; PRED: Prediction of significant EV score.