Table of Contents

Component Description

Chronic liver disease and cirrhosis are significant contributors to morbidity and mortality in the U.S. population. (Singh et al., 2013; Tapper and Parikh, 2018; Yoon and Chen, 2018). With the obesity epidemic, nonalcoholic fatty-liver disease is considered the most common cause of chronic liver disease in U.S. adults and children. Other important causes of chronic liver diseases in the general population include alcoholic liver disease and chronic viral hepatitis infections (C or B).

The main goals of the liver ultrasound transient elastography (variable name prefix LUX) component are to provide objective measures for two important liver disease manifestations: liver fibrosis (scarring in the liver) and hepatic steatosis (fat in the liver). Liver fibrosis was measured by FibroScan® which uses ultrasound and the vibration controlled transient elastography (VCTETM ) to derive liver stiffness. The device also simultaneously measures the ultrasound attenuation related to the presence of hepatic steatosis and records the controlled attenuation parameter (CAPTM) as the indicator for the fatness in the liver. Elastography has been evaluated by others for its accuracy to assess liver steatosis and liver fibrosis (Tang et al, 2015, Castéra et al, 2005, Barr et al, 2015).

Users of this component are strongly encouraged to review the Procedures Manual of this component for a further details.

Eligible Sample

All participants aged 12 years and over were eligible. Participants were excluded if they (1) were unable to lie down on the exam table, (2) were pregnant (or unsure if pregnant) at the time of their exam, or a urine could not be obtained to test for pregnancy, (3) had an implanted electronic medical device, or (4) were wearing a bandage or had lesions on the right side of their abdomen by the ribs (where measurements would be taken).

Protocol and Procedure

A detailed description of the procedures were documented in the Liver Ultrasound Transient Elastography Procedures Manual of this component. The elastography measurements were obtained in the NHANES Mobile Examination Center (MEC), using the FibroScan® model 502 V2 Touch equipped with a medium (M) or extra large (XL) wand (probe).

With FibroScan®, a mechanical vibration of mild amplitude and low frequency (50Hz) is transmitted through the intercostal space using a vibrating tip contacting the skin. The vibration induces a shear wave that propagates through the liver. The displacements induced by the shear waves are tracked and measured using pulse echo ultrasound acquisition algorithms. The shear wave velocity is related directly to tissue stiffness; with harder tissues, there is faster shear wave propagation. Using the Young modulus, the velocity is converted into liver stiffness, and expressed in kilopascals. In systematic reviews comparing VCTETM to biopsy (as a gold standard) for the detection of severe liver fibrosis, the mean area under the ROC curve was 0.89 (95% CI, 0.88-0.91) (Tsochatzis et al, 2011, Friedrich-Rust et al, 2008) and the overall sensitivity and specificity were 82% (95% CI, 78-86%) and 86% (95% CI 0.80-0.91). In addition to the high accuracy, meta-analyses have demonstrated FibroScan® results carry significant prognostic value (Singh et al, 2013). Transient elastography has been FDA approved as a test for the evaluation of liver fibrosis.

The FibroScan® machine has also incorporated a novel physical parameter, CAPTM, which measures the ultrasound attenuation related to the presence of hepatic steatosis. The controlled attenuation parameter measurement is recorded simultaneously with the liver stiffness measurement. The accuracy of the CAPTM measurement for the detection of steatosis against biopsy has been reported in few studies; for steatosis ≥10%, the area under the ROC curve is 0.81, with a sensitivity and specificity of 76% and 79%; for steatosis >34% these values were 0.80, 79% and 71%, respectively. (Myers et al, 2012, de Ledinghen V et al, 2016 Sasso et al, 2016)

The elastography exam was performed by NHANES health technicians, who were trained and certified by NHANES staff and the equipment manufacturer (EchosensTM North America). The exams were performed according to the manufacturer guidelines.

Quality Assurance & Quality Control

A detailed description of quality assurance and quality control measures considered for this component can be found in the Procedures Manual. Briefly, the NHANES health technicians completed a 2-day training program with survey staff and an expert FibroScan® Technician (reference examiner). The training included an overview of the component, demonstrations conducted by the reference examiner with volunteer subjects. The reference examiner reviewed and demonstrated the proper technique of the FibroScan® examination. Supervised practice exercises followed, conducted with several volunteer subjects. The reference examiner would certify the health technician after observing 3 satisfactory exams. The inter-rater reliability (health technician compared with reference examiners, n=32) was 0.86 for stiffness, and 0.94 for CAP-steatosis. With mean differences (SD) for stiffness (E, kPa) =0.44 (1.3), and for steatosis (CAP, dB/m) 4.5 (19.8).

Survey staff members and an external university-based medical epidemiologist with expertise in chronic liver disease, monitored MEC staff performance in the field through periodic visits and direct observations. Health technician performance was also monitored using data reviews for each health technician compared to all other health technicians and annual reference examiner refresher training.

Multiple times per year NHANES staff, including the NHANES Senior Medical Officer, would select a sample of the original FibroScan® PDF files obtained by the health technicians in the MEC for re-review. The samples selected for review include ones from new and experienced health techs, and participants with 1) extreme E, CAP, or E-IQR values, 2) E or CAP values that seemed unusual for younger participants, or 3) inconsistent extreme E and CAP values in the same person (i.e. low E and high CAP or high E and low CAP).

Annual FibroScan® wand calibration was performed by the manufacturer and software updates were performed according to manufacturer recommendations.

In addition, NHANES used four shear wave liver fibrosis phantoms (CIRS Model 039) for determining variances within and between FibroScan® machines and probes over time. For phantom 1 (stiffness mean = 2.6), the intra-machine coefficient of variation (CV) was 1.4%, and inter-machine intra class correlation (ICC) = 3%. For phantom 2 (stiffness mean = 7.0), the intra-machine CV was 1.2%, and inter- machine ICC = 2%. For phantom 3 (stiffness mean = 23.3), the intra-machine CV was 3.2%, and inter- machine ICC = 2%. For phantom 4 (stiffness mean = 56.8), the intra-machine CV was 2.4%, and inter- machine ICC = 22%.

Data Processing and Editing

Information obtained by staff in the MEC regarding pregnancy status/test results, fasting times, possible exam exclusions, and other comments were recorded in the NHANES database during the participant’s MEC visit. All measures recorded by the FibroScan® machines were directly transferred via the Integrated Survey Information System to the NHANES database system immediately after each exam. Health technicians were instructed to visually verify that the values transferred correctly.

Computerized data quality control procedures were performed to check for completeness and data validity and to identify logical inconsistencies and extreme data values (e.g., fasting times lasting more than 40 hours) and rare deviations in the protocol (e.g., technical error for number of measures recorded or duplicate files due to exam restarts).

Prior to data release, NHANES staff reviewed extreme values and cross-checked with other available data for verification and reviewed free-text comments noted by MEC staff and made edits or corrections as appropriate.

The liver elastography exam status code (LUAXSTAT) was created and indicates the following for each participant:
1 = Complete exam (i.e., fasting time of at least 3 hours, 10 or more complete stiffness (E) measures, and a liver stiffness interquartile (IQRe) range / median E < 30%.
2 = Partial exam (i.e., either a fasting time < 3 hours, < 10 complete stiffness (E) measures, or a liver stiffness interquartile (IQRe) range / median E 30% or higher.
3 = Ineligible participant (see eligibility criteria above).
4= Not done (i.e., refusal, limited time during exam visit, other).

Reason codes for partial exams (LUARXNC), exams not done (LUARXND), and ineligible participants (LUARXIN) were created from MEC staff comments and included in this data release.

The number of measures attempted (LUANMTGP) and the number of measures recorded (LUANMVGP), using the final wand, were categorized at high end to 20 to 29, and 30 or more.

FibroScan® measures were not edited, and there are no imputed values in this file.

Elastography results were not reported to participants if they had <10 complete stiffness (E) measures or liver stiffness interquartile (IQRe) range/median E ≥ 30%, or fasted <3 hours, as recommended by the elastography equipment manufacturer. An exception to these criteria was permitted if the participant had an E value below the referral criteria and had at least 10 complete stiffness measures, even though the 3-hour fasting time was not satisfied. In this data file, elastography results are included for all participants regardless of the number of complete stiffness measures, the IQRe value or the length of fast.

Analytic Notes

As stated above no changes were made to the stiffness, controlled attenuation parameter, IQRe, or IQRc values obtained from the FibroScan® machine. Analysts should be aware that some extreme values may be present. Extreme values may be to the result of difficulty obtaining the measures due to participant body habitus (especially those who are obese or who have narrow intercostal spaces), or may represent truly high values.

Sample weights: the NHANES examination sample weights should be used to analyze elastography data unless it is merged with a more restrictive data file, such as the morning fasting sample, then use the sample weight appropriate for that more selective group.

Please refer to the NHANES Analytic Guidelines and the on-line NHANES Tutorials for further details on the use of sample weights and other analytic issues. Both of these are available on the NHANES website.

References

Codebook and Frequencies

SEQN - Respondent sequence number

Variable Name:
SEQN
SAS Label:
Respondent sequence number
English Text:
Respondent sequence number.
Target:
Both males and females 12 YEARS - 150 YEARS

LUAXSTAT - Elastography exam status

Variable Name:
LUAXSTAT
SAS Label:
Elastography exam status
English Text:
Elastography exam status.
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Complete 5494 5494
2 Partial 493 5987
3 Ineligible 258 6245
4 Not done 156 6401
. Missing 0 6401

LUARXNC - Reason for partial exam

Variable Name:
LUARXNC
SAS Label:
Reason for partial exam
English Text:
Reason for partial exam.
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Fasting < 3hrs 257 257
2 Unable to obtain 10 valid measures 129 386
3 IQR/M >30% 107 493
. Missing 5908 6401

LUARXND - Reason exam not done

Variable Name:
LUARXND
SAS Label:
Reason exam not done
English Text:
Reason exam not done.
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Participant refusal 43 43
2 Limited time 42 85
3 Other (e.g. physical or technical limitations ) 71 156
. Missing 6245 6401

LUARXIN - Reason ineligible

Variable Name:
LUARXIN
SAS Label:
Reason ineligible
English Text:
Reason ineligible.
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Pregnant/ Unable to get urine to test for pregnancy 93 93
2 Other (e.g. insulin pump or other implantable electronic device) 165 258
. Missing 6143 6401

LUAPNME - Exam wand type

Variable Name:
LUAPNME
SAS Label:
Exam wand type
English Text:
Exam wand type.
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
M M 4478 4478
XL XL 1508 5986
< blank > Missing 415 6401

LUANMVGP - Count:complete measures from final wand

Variable Name:
LUANMVGP
SAS Label:
Count:complete measures from final wand
English Text:
Total number of complete measures retained (using final wand).
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 1 11 11
2 2 10 21
3 3 11 32
4 4 15 47
5 5 7 54
6 6 8 62
7 7 9 71
8 8 8 79
9 9 12 91
10 10 3170 3261
11 11 823 4084
12 12 547 4631
13 13 374 5005
14 14 274 5279
15 15 219 5498
16 16 134 5632
17 17 92 5724
18 18 74 5798
19 19 34 5832
20 20 to 29 98 5930
30 30 or more 20 5950
. Missing 451 6401

LUANMTGP - Count:measures attempted with final wand

Variable Name:
LUANMTGP
SAS Label:
Count:measures attempted with final wand
English Text:
Total number of measures attempted (using final wand).
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0 Not done 415 415
1 1 1 416
3 3 1 417
4 4 1 418
5 5 2 420
6 6 1 421
9 9 2 423
10 10 1442 1865
11 11 778 2643
12 12 551 3194
13 13 495 3689
14 14 378 4067
15 15 347 4414
16 16 249 4663
17 17 189 4852
18 18 178 5030
19 19 149 5179
20 20 to 29 682 5861
30 30 or more 540 6401
. Missing 0 6401

LUATECH - Health technician code

Variable Name:
LUATECH
SAS Label:
Health technician code
English Text:
Health technician code.
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
A A 176 176
B B 478 654
C C 485 1139
D D 847 1986
E E 820 2806
F F 815 3621
G G 815 4436
H H 769 5205
I I 247 5452
J J 733 6185
YY Other staff 216 6401
< blank > Missing 0 6401

LUXSMED - Median stiffness (E), kilopascals (kPa)

Variable Name:
LUXSMED
SAS Label:
Median stiffness (E), kilopascals (kPa)
English Text:
Median liver stiffness (E) This indicator is presented with one digit to the right of the decimal ratio (e.g. XX.X), and the units for this measure are kilopascals (kPa).
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1.6 to 75 Range of Values 5950 5950
. Missing 451 6401

LUXSIQR - Stiffness E interquartile range (IQRe)

Variable Name:
LUXSIQR
SAS Label:
Stiffness E interquartile range (IQRe)
English Text:
Stiffness (E) interquartile range (IQRe) of final stiffness measures. This indicator is presented with one digit to the right of the decimal, (e.g. XX.X).
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0 to 66.9 Range of Values 5957 5957
. Missing 444 6401

LUXSIQRM - Ratio: Stiffness IQRe / median E

Variable Name:
LUXSIQRM
SAS Label:
Ratio: Stiffness IQRe / median E
English Text:
Ratio of the stiffness IQRe / median E stiffness value. This indicator is presented as a percent with one digit to the right of the decimal, (e.g. XX.X %).
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0 to 1338 Range of Values 5942 5942
. Missing 459 6401

LUXCAPM - Median CAP, decibels per meter (dB/m)

Variable Name:
LUXCAPM
SAS Label:
Median CAP, decibels per meter (dB/m)
English Text:
Median controlled attenuated parameter (CAP) This indicator is presented as a whole number XXX, and the units for this measure are decibels per meter (dB/m).
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
100 to 400 Range of Values 5948 5948
. Missing 453 6401

LUXCPIQR - CAP interquartile range (IQRc)

Variable Name:
LUXCPIQR
SAS Label:
CAP interquartile range (IQRc)
English Text:
Controlled attenuated parameter (CAP) interquartile range (IQRc) of final CAP measures. This indicator is presented as a whole number (e.g. XX).
Target:
Both males and females 12 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0 to 206 Range of Values 5940 5940
. Missing 461 6401