SUPPLEMENTARY MATERIAL
Supplementary Table 1. Search engine in EMBASE and PUBMED (last upadated
03/17/2010) ..................................................................................................................... 2
Supplementary Table 2. Characteristics of the studies that provided data on intra- or
inter-observer reliability, chronologically ordered ............................................................ 3
Supplementary table 3. Sensitivity and Specificity in by different histology cut-offs ........ 4
Supplementary Table 4. Diagnostic accuracy of the different components of the
ultrasound evaluation. ..................................................................................................... 4
Supplementary Table 5. Reliability studies estimates by method of assessment ............ 5
Supplementary Table 6. Comparative analysis in studies that used ultrasonography,
histology and other imaging technique. ........................................................................... 7
Supplementary Figure 1. Flowchart of the study (October 1967 to March, 17 th, 2010 .... 8
Supplementary Figure 2. Sensitivity Analyses among for ultrasound to detect
histologically defined steatosis. ....................................................................................... 9
References- Supplementary Material ............................................................................ 10
Supplementary Material 1
Supplementary Table 1. Search engine in EMBASE and PUBMED (last upadated
03/17/2010)
EMBASE:
'echography'/exp OR 'echography' OR 'ultrasound'/exp OR 'ultrasound' OR
'ultrasonography'/exp OR 'ultrasonography' OR ultrasounds AND ('fatty liver'/exp OR 'fatty liver'
OR 'steatosis'/exp OR 'steatosis' OR 'steatohepatitis' OR nafld OR nash OR 'bright liver' OR
'echogenic liver' OR 'hyperechogenic liver') AND [embase]/lim
PUBMED:
((echography/exp OR echography) OR (ultrasound/exp OR ultrasound) OR
(ultrasonography/exp OR ultrasonography) OR ultrasounds) AND ((fatty liver/exp OR fatty liver)
OR (steatosis/exp OR steatosis) OR steatohepatitis OR nafld OR nash OR bright liver OR
echogenic liver OR hyperechogenic liver)
Supplementary Material 2
Supplementary Table 2. Characteristics of the studies that provided data on intraor inter-observer reliability, chronologically ordered
Indication
US/Standard
Suspicion liver
disease
Known liver
disease
Liver
Disease
Stand
ard
Histolo
gy
Histolo
gy
N (pairs of reliability
analyses)
N/A
58
Author, year (ref.)
Country
Setting
Debongnie, 1981 (1)
Belgium
N/R
Sanford, 1985 (2)
Australia
Hospital
Brodkin, 1995(3)
USA
General population
Graif, 2000 (4)
Israel
N/R
Sadeeh, 2002 (5)
USA
Outpatient clinic
Chan, 2004 (6)
China
Outpatient clinic
Suspicion liver
disease
Known liver
disease
Health screening
Magalotti, 2004 (7)
Italy
Outpatient clinic
Other
NAFLD
Vehmas, 2004 (8)
Finland
General population
Suspicion liver
disease
N/R
N/A
22
Fishbein, 2005 (9)
USA
Mixed
(inpatient/outpatient
)
Known liver
disease
Mixed
Histolo
gy
38
Capanni, 2006 (10)
Italy
Outpatient clinic
NAFLD
N/A
12
Holt, 2006 (11)
UK
General population
Known liver
disease
Other
NAFLD
N/A
22
Liu, 2006 (12)
Mendez Sanchez,
2006(13)
China
General population
Health screening
NAFLD
N/A
17
Mexico
Outpatient clinic
Health screening
Mixed
N/a
141
Riley, 2006 (14)
USA
Outpatient clinic
Known liver
disease
Mixed
Histolo
gy
10
Outpatient clinic
Health screening
NAFLD
N/A
30
General population
NAFLD
N/A
Mixed
N/A
Histolo
gy
N/A
Health screening
Mixed
Mixed
No
NAFLD
Mixed
NAFLD
NAFLD
Histolo
gy
Histolo
gy
N/A
Histolo
gy
77
125
28
25
84 * (used consensus)
20
Chang, 2007 (16)
Netherla
nds
Korea
Liang, 2007 (17)
Taiwan
Hospital
Strauss, 2007 (18)
Israel
N/R
Health screening
Suspicion liver
disease
Mixed
D’Adamo, 2008 (19)
Italy
Outpatient clinic
Health screening
NAFLD
N/A
10
Fallo, 2008 (20)
Italy
Outpatient clinic
Health screening
NAFLD
N/A
120
Jun, 2008 (21)
Korea
Outpatient clinic
Mixed
NAFLD
408
Soresi, 2009(22)
Italy
N/R
Mixed
Mixed
N/A
Histolo
gy
Brouwers, 2007 (15)
NAFLD
60
168
150
Supplementary Material 3
Supplementary Table 3. Sensitivity and Specificity in by different histology cutoffs
New cut offs Sensitivity
>0-5%
0.65
(0.51, 0.76)
≥10%
0.93
(0.88, 0.97)
≥20-30%
0.91
(0.68, 0.98)
N/R
0.78
(0.71, 0.84)
Specificity
0.81
(0.70, 0.88)
0.88
(0.63, 0.97)
0.99
(0.75, 1.00)
0.97
(0.92, 0.99)
Supplementary Table 4. Diagnostic accuracy of the different components of the
ultrasound evaluation.
N
7
Sensitivity
Specificity
LR+
LRLiver to kidney
0.98 (0.75,
0.93 (0.69,
14.0 (2.6, 74.9)
0.02 (0, 0.37)
contrast
1.00)
0.99)
Deep beam
7
0.59 (0.45,
0.95 (0.80,
0.43 (0.32,
11.7 (3.1, 44.5)
attenuation
0.72)
0.99)
0.57)
7
0.81 (0.70,
0.98 (0.71,
0.19 (0.12,
Vessel (porta*)
43.5 (2.2, 853.7)
0.89)
1.00)
0.31)
7
0.85 (0.70,
0.98 (0.66,
47.5 (1.88,
0.15 (0.07,
Vessel (hepatic*)
0.93)
1.00)
1196.94)
0.32)
2
0.62 (0.50,
1.00 (0.97,
0.38 (0.29,
Gall bladder walls
∞ (N/A)
0.73)
1.00)
0.51)
4
0.85 (0.79,
0.94 (0.87,
Overall
13.3 (6.4-27.6)
0.16 (0.12-0.22)
9
0.89)
0.97)
*Ferrari and Dasarathy reported two different accuracy estimates for the evaluation of porta vein and
hepatic vein
Supplementary Material 4
Supplementary Table 5. Reliability studies estimates by method of assessment
Author
Fallo(20)
Reliability
estimate
Correlation
Compo
nent
Number
readers
2
# intra-reader
studies
120
Estimate Intrareader
0.945
# inter-reader
studies
120
Estimate Interreader
0.88
Magalotti
(7)
Capanni(
10)
D’Adamo
(19)
Debongn
ie (1)
Vehmas,
2004 (8)
Sandford
(2)
Sandford
(2)
Brodkin(
3)
Graif(4)
CV
1
CV
1
12
<5%
CV
1
10
<1%
Disagreement
1
104
9%
ICC
3
0.47a
Kappa
2
0.44
2
0.39
Kappa
DBA
<5%
Kappa
3
Kappa
3
Sadeeh(
5)
Chan (6)
Kappa
2
Kappa
2
0.89d
Fishbein(
9)
Holt(11)
Kappa
2
0.78
Kappa
2
22
0.93
Liu(12)
Kappa
2
17
1
Mendez
Sanchez
(13)
Riley(14)
Kappa
1
141
0.92
Kappa
15
10
Brouwer
s(15)
Brouwer
s(15)
Chang(1
6)
Liang
(17)
Liang
(17)
Liang
(17)
Liang
(17)
Liang
(17)
Kappa
1
30
0.68 (0.62,
0.74)
0.74
1
30
0.68
Kappa
Par (4)
Kappa
Kappa
Kappa
Kappa
Kappa
Kappa
58
0.62b
0.57c
25
0.63 (0.26,
0.90)
25
0.4 (0.07, 0.72)
3
Fatty
liver
Par (4)
DBA
GBW
Portal
vein
0.98
2
60
0.79 (0.69-0.89)
60
0.53 (0.40-0.66)
2
60
0.87 (0.78-0.96)
60
0.65 (0.53-0.77)
2
60
0.76 (0.65-0.87)
60
0.65 (0.53-0.77)
2
60
0.82 (0.72-0.92)
60
0.75 (0.64-0.86)
2
60
0.65 (0.53-0.77)
60
0.61 (0.49-0.73)
Supplementary Material 5
Supplementary Table 5. Reliability studies estimates by method of assessment
(cont’d)
Author
Liang(1
7)
Strauss
(18)
Strauss
(18)
Jun(21)
Soresi(
22)
Soresi(
22)
Reliability
estimate
Kappa
Compo
nent
Hepatic
vein
Kappa
Kappa
Severity
(4)
Number
readers
# intra-reader
studies
Estimate Interreader
60
0.75 (0.64-0.86)
60
0.57 (0.44-0.70)
3
168
0.54
168
0.46
168
0.49
408
0.64
0.79 (0.600.82)
0.86 (0.780.91)
3
2
Kappa
2
DBA
# inter-reader
studies
2
Kappa
Kappa
Estimate Intrareader
168
2
0.58
DBA: deep beam attenuation, Par.: parenchyma; GBW: gallbladder walls
Supplementary Material 6
Supplementary Table 6. Comparative analysis in studies that used ultrasonography, histology and other imaging
technique.
Author (ref.)
Lee(23)
Yamashiki(24)
Lee(25)
Year
country
2007
Korea
2009
2010
Japan
Korea
Histology cut-off
Fat%
>=30
>=10
>=30
Technique
Cut-off
TP
TN
FP
FN
SN
SP
US
LKC+vessels+DBA
60
407
117
5
0.923
0.777
CT
>10 HU lower than spleen
42
474
117
23
0.646
0.802
US
NR
7
53
16
2
0.778
0.768
CT
LS ratio <1.1
6
65
4
3
0.667
0.942
US
moderate/severe
9
147
3
2
0.818
0.980
CT
3.2
8
137
13
3
0.727
0.913
US
moderate/severe
9
147
3
2
0.818
0.980
MRS
7.7
8
119
31
3
0.727
0.793
US
moderate/severe
9
147
3
2
0.818
0.980
MRI
6.5
10
141
9
1
0.909
0.940
Abbreviations: TP true positives, TN: true negatives, FP: false positives; FN: False negatives: SN: sensitivity; SP: specificity. CT: Computerized
tomography; MRS: magnetic resonance spectroscopy; MRI: magnetic resonance imaging; US: ultrasounds.
Supplementary Material 7
Supplementary Figure 1. Flowchart of the study (October 1967 to March, 17th,
2010
Supplementary Material 8
Supplementary Figure 2. Sensitivity Analyses among for ultrasound to detect histologically defined steatosis.
Supplementary Material 9
References- Supplementary Material
1. Debongnie JC, Pauls C, Fievez M, Wibin E. Prospective evaluation of the diagnostic
accuracy of liver ultrasonography. Gut 1981 Feb;22(2):130-135.
2. Sanford NL, Walsh P, Matis C, Baddeley H, Powell LW. Is ultrasonography useful in the
assessment of diffuse parenchymal liver disease? Gastroenterology 1985 Jul;89(1):186191.
3. Brodkin CA, Daniell W, Checkoway H, Echeverria D, Johnson J, Wang K, et al. Hepatic
ultrasonic changes in workers exposed to perchloroethylene. Occup Environ Med 1995
Oct;52(10):679-685.
4. Graif M, Yanuka M, Baraz M, Blank A, Moshkovitz M, Kessler A, et al. Quantitative
estimation of attenuation in ultrasound video images: correlation with histology in diffuse
liver disease. Invest Radiol 2000 May;35(5):319-324.
5. Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of
radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002
Sep;123(3):745-750.
6. Chan DF, Li AM, Chu WC, Chan MH, Wong EM, Liu EK, et al. Hepatic steatosis in
obese Chinese children. Int J Obes Relat Metab Disord 2004 Oct;28(10):1257-1263.
7. Magalotti D, Marchesini G, Ramilli S, Berzigotti A, Bianchi G, Zoli M. Splanchnic
haemodynamics in non-alcoholic fatty liver disease: effect of a dietary/pharmacological
treatment. A pilot study. Dig Liver Dis 2004 Jun;36(6):406-411.
8. Vehmas T, Kaukiainen A, Luoma K, Lohman M, Nurminen M, Taskinen H. Liver
echogenicity: measurement or visual grading? Comput Med Imaging Graph 2004
Jul;28(5):289-293.
9. Fishbein M, Castro F, Cheruku S, Jain S, Webb B, Gleason T, et al. Hepatic MRI for fat
quantitation: its relationship to fat morphology, diagnosis, and ultrasound. J Clin
Gastroenterol 2005 Aug;39(7):619-625.
10. Capanni M, Calella F, Biagini MR, Genise S, Raimondi L, Bedogni G, et al. Prolonged n3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients
with non-alcoholic fatty liver disease: a pilot study. Aliment Pharmacol Ther 2006 Apr
15;23(8):1143-1151.
11. Holt HB, Wild SH, Wood PJ, Zhang J, Darekar AA, Dewbury K, et al. Non-esterified fatty
acid concentrations are independently associated with hepatic steatosis in obese
subjects. Diabetologia 2006 Jan;49(1):141-148.
12. Liu KH, Chan YL, Chan JC, Chan WB, Kong WL. Mesenteric fat thickness as an
independent determinant of fatty liver. Int J Obes (Lond) 2006 May;30(5):787-793.
Supplementary Material 10
13. Mendez-Sanchez N, Chavez-Tapia NC, Medina-Santillan R, Villa AR, Sanchez-Lara K,
Ponciano-Rodriguez G, et al. The efficacy of adipokines and indices of metabolic
syndrome as predictors of severe obesity-related hepatic steatosis. Dig Dis Sci 2006
Oct;51(10):1716-1722.
14. Riley TR, III, Mendoza A, Bruno MA. Bedside ultrasound can predict nonalcoholic fatty
liver disease in the hands of clinicians using a prototype image. Dig Dis Sci 2006
May;51(5):982-985.
15. Brouwers MC, Bilderbeek-Beckers MA, Georgieva AM, van der Kallen CJ, van
Greevenbroek MM, de Bruin TW. Fatty liver is an integral feature of familial combined
hyperlipidaemia: relationship with fat distribution and plasma lipids. Clin Sci (Lond) 2007
Jan;112(2):123-130.
16. Chang Y, Ryu S, Sung E, Jang Y. Higher concentrations of alanine aminotransferase
within the reference interval predict nonalcoholic fatty liver disease. Clin Chem 2007
Apr;53(4):686-692.
17. Liang RJ, Wang HH, Lee WJ, Liew PL, Lin JT, Wu MS. Diagnostic value of
ultrasonographic examination for nonalcoholic steatohepatitis in morbidly obese patients
undergoing laparoscopic bariatric surgery. Obes Surg 2007 Jan;17(1):45-56.
18. Strauss S, Gavish E, Gottlieb P, Katsnelson L. Interobserver and intraobserver variability
in the sonographic assessment of fatty liver. AJR Am J Roentgenol 2007
Dec;189(6):W320-W323.
19. D'Adamo E, Impicciatore M, Capanna R, Loredana MM, Masuccio FG, Chiarelli F, et al.
Liver steatosis in obese prepubertal children: a possible role of insulin resistance.
Obesity (Silver Spring) 2008 Mar;16(3):677-683.
20. Fallo F, Dalla PA, Sonino N, Federspil G, Ermani M, Baroselli S, et al. Nonalcoholic fatty
liver disease, adiponectin and insulin resistance in dipper and nondipper essential
hypertensive patients. J Hypertens 2008 Nov;26(11):2191-2197.
21. Jun DW, Han JH, Kim SH, Jang EC, Kim NI, Lee JS, et al. Association between low
thigh fat and non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2008
Jun;23(6):888-893.
22. Soresi M, Giannitrapani L, Florena AM, La SE, Di G, V, Rappa F, et al. Reliability of the
bright liver echo pattern in diagnosing steatosis in patients with cryptogenic and HCVrelated hypertransaminasaemia. Clin Radiol 2009 Dec;64(12):1181-1187.
23. Lee JY, Kim KM, Lee SG, Yu E, Lim YS, Lee HC, et al. Prevalence and risk factors of
non-alcoholic fatty liver disease in potential living liver donors in Korea: a review of 589
consecutive liver biopsies in a single center. J Hepatol 2007 Aug;47(2):239-244.
24. Yamashiki N, Sugawara Y, Tamura S, Kaneko J, Matsui Y, Togashi J, et al. Noninvasive
estimation of hepatic steatosis in living liver donors: usefulness of visceral fat area
measurement. Transplantation 2009 Aug 27;88(4):575-581.
Supplementary Material 11
25. Lee SS, Park SH, Kim HJ, Kim SY, Kim MY, Kim DY, et al. Non-invasive assessment of
hepatic steatosis: prospective comparison of the accuracy of imaging examinations. J
Hepatol 2010 Apr;52(4):579-585.
Supplementary Material 12