Supplementary Table 1. Search Strategy Information Search date: March 24, 2022
Databases searched: PubMed MEDLINE, Cochrane, CINAHL, Scopus, Web of Science, SPORT Discus
Limits: English
# Searches Results
PubMed MEDLINE
1 "non-alcoholic fatty liver disease"[mesh] 18358
2 "fatty liver"[mesh] 40424
3 NAFLD[tiab] 19780
4 "non-alcoholic steatohepatitis"[tiab] 5314 5 "nonalcoholic steatohepatits"[tiab] 6797
6 NASH[tiab] 11090
7 "fatty liver"[tiab] 36919
8 or/1-7 57887
9 exercise[mesh] 228057
10 exercis*[tiab] 336220
11 "healthy lifestyle"[mesh] 10489
12 "physical activity"[tiab] 131368
13 "healthy living"[tiab] 1554
14 "health status"[tiab] 67146
15 "sedentary behavior"[mesh] 12310
16 sedentary[tiab] 36369
17 lifestyle[tiab] 114208
18 "life style"[tiab] 11662
19 "life style"[mesh] 105417
20 "physical inactivity"[tiab] 9401
21 "health status"[mesh] 398914
22 "health level"[tiab] 1151
23 "level of health"[tiab] 1938
24 "activity level"[tiab] 14075
25 "exercise therapy"[mesh] 59189
26 or/9-25 1074855
27 "magnetic resonance imaging"[mesh] 505797 28 "diffusion magnetic resonance imaging"[mesh] 33137 29 "magnetic resonance imaging, interventional"[mesh] 1834 30 "liver/diagnostic imaging"[mesh] 18468
31 MRI[tiab] 288957
32 "magnetic resonance imag*"[tiab] 280294
33 "liver fat"[tiab] 3295
34 PDFF[tiab] 520
35 "proton density fat fraction"[tiab] 649 36 "noninvasive quantitative biomarker"[tiab] 4
37 or/27-36 686581
38 8 AND 26 AND 37 403
39 38 AND (english[Filter]) 391
40 39 AND (humans[Filter]) 325
41 40 AND (adults[Filter]) 186
42 41 AND (clinical trials[Filter]) 74
# Searches Results
CINAHL
1 "fatty liver" 6837
2 NAFLD 3730
3 "non-alcoholic steatohepatitis" 545
4 "nonalcoholic steatohepatitis" 1158
5 NASH 1527
6 or/1-5 8282
7 exercis* 134574
8 "physical activity" 68004
9 "healthy living" 1697
10 "health status" 28336
11 sedentary 14279
12 lifestyle 52694
13 "life style" 2287
14 "physical inactivity" 4175
15 "health level" 425
16 "level of health" 1915
17 "activity level" 5459
18 or/7-17 262237
19 "magnetic resonance imag*" 62903
20 MRI 67988
21 "liver fat" 790
22 PDFF 169
23 "noninvasive quantitative biomarker" 1 24 "non-invasive quantitative biomarker" 1
25 or/19-23 104227
26 6 AND 18 AND 25 78
27 26 AND [English filter] 75
28 27 AND (adults[Filter]) 25
# Searches Results
Scopus
1 "fatty liver" 40182
2 NAFLD 20218
3 "non-alcoholic steatohepatitis" 5132
4 "nonalcoholic steatohepatitis" 6692
5 NASH 44180
6 or/1-5 82148
7 exercis* 541472
8 "physical activity" 169034
9 "healthy living" 2963
10 "health status" 88462
11 sedentary 47773
12 lifestyle 173899
13 "life style" 22255
14 "physical inactivity" 11160
15 "health level" 2834
16 "level of health" 5794
17 "activity level" 47173
18 or/7-17 959889
19 "magnetic resonance imag*" 308226
20 MRI 346725
21 "liver fat" 3756
22 PDFF 561
23 "noninvasive quantitative biomarker" 3 24 "non-invasive quantitative biomarker" 4
25 or/19-23 517890
26 6 AND 18 AND 25 261
27 26 AND [English filter] 245
28 27 AND (clinical trials[Filter]) 181
# Searches Results
Web of Science
1 "fatty liver" 39802
2 NAFLD 20886
3 "non-alcoholic steatohepatitis" 5762
4 "nonalcoholic steatohepatitis" 7200
5 NASH 39748
6 or/1-5 80843
7 exercis* 456260
8 "physical activity" 157999
9 "healthy living" 2297
10 "health status" 70155
11 sedentary 42265
12 lifestyle 144131
13 "life style" 12870
14 "physical inactivity" 9488
15 "health level" 1548
16 "level of health" 2058
17 "activity level" 16760
18 or/7-17 795022
19 "magnetic resonance imag*" 274976
20 MRI 306465
21 "liver fat" 3675
22 PDFF 555
23 "noninvasive quantitative biomarker" 3 24 "non-invasive quantitative biomarker" 3
25 or/19-23 466215
26 6 AND 18 AND 25 241
27 26 AND [English filter] 234
28 27 AND (clinical trials[Filter]) 162
# Searches Results
SPORT Discus
1 "fatty liver" 600
2 NAFLD 325
3 "non-alcoholic steatohepatitis" 97
4 "nonalcoholic steatohepatitis" 36
5 NASH 671
6 or/1-5 1261
7 exercis* 150561
8 "physical activity" 47574
9 "healthy living" 545
10 "health status" 3503
11 sedentary 10828
12 lifestyle 15444
13 "life style" 816
14 "physical inactivity" 1697
15 "health level" 125
16 "level of health" 255
17 "activity level" 3092
18 or/7-17 204379
19 "magnetic resonance imag*" 7607
20 MRI 6467
21 "liver fat" 155
22 PDFF 4
26 or/19-23 10930
27 6 AND 18 AND 26 12
28 27 AND [English filter] 11
Supplementary Table 2. Studies excluded after full-text review 1-23
1. Bacchi E, Negri C, Targher G, et al. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial).
Hepatology 2013;58:1287-95. No standard of care comparator.
2. Barsalani R, Riesco E, Lavoie JM, et al. Effect of exercise training and isoflavones on hepatic steatosis in overweight postmenopausal women. Climacteric 2013;16:88-95. No MRI outcome.
3. Cassidy S, Thoma C, Hallsworth K, et al. High intensity intermittent exercise improves cardiac structure and function and reduces liver fat in patients with type 2 diabetes: a randomised controlled trial.
Diabetologia 2016;59:56-66. Not NAFLD patients.
4. Charatcharoenwitthaya P, Kuljiratitikal K, Aksornchanya O, et al. Moderate-Intensity Aerobic vs Resistance Exercise and Dietary Modification in Patients With Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial. Clin Transl Gastroenterol 2021;12:e00316. No MRI outcome.
5. Eckard C, Cole R, Lockwood J, et al. Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial. Therap Adv Gastroenterol 2013;6:249-59. No MRI outcome.
6. Hickman IJ, Jonsson JR, Prins JB, et al. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut 2004;53:413-9. No MRI outcome.
7. Jia GY, Han T, Gao L, et al. [Effect of aerobic exercise and resistance exercise in improving non- alcoholic fatty liver disease: a randomized controlled trial]. Zhonghua Gan Zang Bing Za Zhi 2018;26:34-41. No MRI outcome.
8. Johnson NA, Sachinwalla T, Walton DW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 2009;50:1105-12. Not NAFLD patients.
9. Kantartzis K, Thamer C, Peter A, et al. High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease. Gut 2009;58:1281- 8. No standard of care comparator.
10. Keating SE, Hackett DA, Parker HM, et al. Effect of aerobic exercise training dose on liver fat and visceral adiposity. J Hepatol 2015;63:174-82. Not NAFLD patients.
11. Keating SE, Hackett DA, Parker HM, et al. Effect of resistance training on liver fat and visceral adiposity in adults with obesity: A randomized controlled trial. Hepatol Res 2017;47:622-631. Not NAFLD
patients.
12. Lee S, Bacha F, Hannon T, et al. Effects of aerobic versus resistance exercise without caloric restriction on abdominal fat, intrahepatic lipid, and insulin sensitivity in obese adolescent boys: a randomized, controlled trial. Diabetes 2012;61:2787-95. Not NAFLD patients.
13. Motiani KK, Savolainen AM, Toivanen J, et al. Effects of short-term sprint interval and moderate-
intensity continuous training on liver fat content, lipoprotein profile, and substrate uptake: a randomized trial. J Appl Physiol (1985) 2019;126:1756-1768. No standard of care comparitor.
14. O'Gorman P, Naimimohasses S, Monaghan A, et al. Improvement in histological endpoints of MAFLD following a 12-week aerobic exercise intervention. Aliment Pharmacol Ther 2020. No MRI outcome.
15. Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010;51:121-9. No MRI outcome.
16. Rezende RE, Duarte SM, Stefano JT, et al. Randomized clinical trial: benefits of aerobic physical activity for 24 weeks in postmenopausal women with nonalcoholic fatty liver disease. Menopause 2016;23:876-83. No MRI outcome.
17. Shamsoddini A, Sobhani V, Ghamar Chehreh ME, et al. Effect of Aerobic and Resistance Exercise Training on Liver Enzymes and Hepatic Fat in Iranian Men With Nonalcoholic Fatty Liver Disease.
Hepat Mon 2015;15:e31434. No MRI outcome.
18. Shi X, Yin H, Li J, et al. Circulating branch chain amino acids and improvement in liver fat content in response to exercise interventions in NAFLD. Sci Rep 2021;11:13415. Duplicate patient data (Zhang et al. 2016)
19. Slentz CA, Bateman LA, Willis LH, et al. Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT.
Am J Physiol Endocrinol Metab 2011;301:E1033-9. Not NAFLD patients.
20. Wong VW, Chan RS, Wong GL, et al. Community-based lifestyle modification programme for non- alcoholic fatty liver disease: a randomized controlled trial. J Hepatol 2013;59:536-42. Not exercise training intervention.
21. Yaskolka Meir A, Keller M, Müller L, et al. Effects of lifestyle interventions on epigenetic signatures of liver fat: Central randomized controlled trial. Liver Int 2021;41:2101-2111. No standard of care comparitor.
22. Yoshimura E, Kumahara H, Tobina T, et al. Lifestyle intervention involving calorie restriction with or without aerobic exercise training improves liver fat in adults with visceral adiposity. J Obes
2014;2014:197216. Not NAFLD patients.
23. Zelber-Sagi S, Buch A, Yeshua H, et al. Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial. World J Gastroenterol 2014;20:4382-92. No MRI outcome.
Supplementary Figure 1. Risk of bias. The majority of included studies were adjudicated to have low bias.
Supplementary Figure 2. Publication bias. No significant publication bias was observed.
Supplementary Figure 3. Sensitivity Analysis. No significant differences in results were observed when excluding the large, longer duration study by Zhang et al.(22)
(A)
The pooled mean difference in absolute change in MRI-measured liver fat for exercise training versus the control condition was -6.1%, 95% CI -8.8 to -3.3% (p<0.001).
(B)