Table 1.
Characteristics of 48 meta-analyses of RCTs on therapies that improve NAFLD
| Exposure | Author, year | Measure | Studies (n) | Subjects (n) | Cases (n) | Random effect model Effect size (95% CI) |
p-value | I2 (%) | Heterogeneity p-value |
Small-study effects p-value |
|
|---|---|---|---|---|---|---|---|---|---|---|---|
| Caffeine [26] | Shen2016 | Liver fibrosis | 2 | NR | 292 | MD | −91.35 (−139.42, −43.27) | 0.0002 | 0 | 0.74 | NA |
| Green tea [25] | Ghanaei2018 | ALT | 4 | 234 | 122 | MD | −12.81 (−18.17, −7.45) | <0.00001 | 9 | 0.35 | 0.75 |
| Green tea [25] | Ghanaei2018 | AST | 4 | 234 | 122 | MD | −10.91 (−19.66, −2.17) | 0.01 | 80 | 0.002 | 0.32 |
| Green tea [25] | Ghanaei2018 | TG | 3 | 163 | 87 | MD | −31.86 (−40.62, −23.12) | <0.00001 | 0 | 0.53 | 0.71 |
| Green tea [25] | Ghanaei2018 | TC | 3 | 163 | 87 | MD | −27.57 (−36.17, −18.98) | <0.00001 | 3 | 0.36 | 0.82 |
| Green tea [25] | Ghanaei2018 | LDL | 3 | 163 | 87 | MD | −14.15 (−23.69, −4.60) | 0.004 | 34 | 0.22 | 0.77 |
| Green tea [25] | Ghanaei2018 | BMI | 4 | 234 | 122 | MD | −2.08 (−2.81, −1.36) | <0.00001 | 0 | 0.49 | 0.06 |
| Low carbohydrate diet [27] | Haghighatdoos2016 | IHLC | 4 | NA | 238 |
Mean percentage |
−11.53% (−18.10, −4.96) | 0.00085 | 83.2 | <0.001 | 0.34 |
| Omega-3 PUFAs [63] | Yan2018 | ALT | 14 | 937 | NA | SMD | −0.50 (−0.88, −0.11) | 0.000 | 86.4 | <0.001 | 0.695 |
| Omega-3 PUFAs [63] | Yan2018 | AST | 12 | 903 | NA | SMD | −0.54 (−1.04, −0.05) | 0.000 | 91.2 | <0.001 | 0.733 |
| Omega-3 PUFAs [63] | Yan2018 | GGT | 8 | 1121 | NA | SMD | −0.48 (−0.64, −0.31) | 0.013 | 41.6 | 0.101 | 0.945 |
| Omega-3 PUFAs [63] | Yan2018 | HOMR-IR | 8 | 502 | NA | SMD | −0.40 (−0.58, −0.22) | 0.001 | 16.6 | 0.299 | 0.259 |
| Omega-3 PUFAs [63] | Yan2018 | Glucose | 8 | 474 | NA | SMD | −0.25 (−0.43, −0.06) | 0.002 | 43 | 0.092 | 0.274 |
| Omega-3 PUFAs [63] | Yan2018 | TG | 16 | 1075 | NA | SMD | −0.47 (−0.76, −0.19) | 0.002 | 79.6 | <0.001 | 0.469 |
| Omega-3 PUFAs [59] | Musa-Veloso 2017 | Liver fat content | 5 | NA | NA | MD | −5.19% (−9.58, −0.97) | 0.021 | NA | NA | NA |
| Omega-3 PUFAs [59] | Musa-Veloso 2017 | Grade of steatosis | 7 | NA | NA | MD | −0.71 (−0.99, −0.42) | <0.001 | NA | NA | NA |
| Omega-3 PUFAs [28] | Parker2012 | Liver fat | 7 | NA | 355 | ES | −0.97 (−0.58, −1.35) | <0.001 | 66.12 | 0.007 | NA |
| Omega-3 PUFAs [58] | Yu2017 | LDL | 6 | 468 | 235 | MD | −9.18 (−14.89, −3.47) | 0.002 | 43 | 0.13 | NA |
| Omega-3 PUFAs [58] | Yu2017 | HDL | 7 | 509 | 254 | MD | 4.81 (1.59, 8.03) | 0.03 | 65 | 0.009 | NA |
| Total exercise [60] | Smart 2016 | Intrahepatic fat | 21 | 1530 | NA | SMD | −1.77 (−3.11, −0.42) | 0.01 | 77 | NA | 0.1 |
| Total exercise (irrespectively of weight change) [61] | Katsagoni2016 | IHTG | 10 | 540 | 325 | SMD | −0.98 (−1.30, −0.66) | <0.001 | 62.1 | 0.002 | 0.012 |
| Total exercise (irrespectively of weight change) [61] | Katsagoni2016 | ALT | 11 | 495 | 301 | SMD | −0.39 (−0.66, −0.11) | 0.006 | 55.3 | 0.008 | 0.015 |
| Total exercise (irrespectively of weight change) [61] | Katsagoni2016 | AST | 9 | 494 | 373 | SMD | −0.37 (−0.65, −0.09) | 0.009 | 53.7 | 0.017 | 0.016 |
| Total exercise (irrespectively of weight change) [61] | Katsagoni2016 | WC | NA | 564 | NA | SMD | −0.6 (−0.78, −0.42) | <0.001 | 0 | 0.71 | NA |
| Total exercise (irrespectively of weight change) [61] | Katsagoni2016 | HOMA-IR | NA | 564 | NA | SMD | −0.76 (−1.47, −0.05) | <0.001 | 8 | <0.001 | NA |
| Total exercise (irrespectively of weight change) [22] | Keating2012 | Liver fat | 6 | 156 | 93 | ES | −0.37 (−0.69, −0.06) | 0.02 | NA | NA | NA |
| Exercise (AEx) [ 61] | Katsagoni2016 | IHTG | 5 | 119 | 68 | SMD | −0.84 (−1.27, −0.42) | <0.001 | 66.6 | NA | NA |
| Exercise (RT) [61] | Katsagoni2016 | IHTG | 3 | 133 | 72 | SMD | −1.05 (−1.87, −0.24) | 0.011 | 65.1 | NA | NA |
| Exercise (AEx + RT) [ 61] | Katsagoni2016 | IHTG | 3 | 61 | 36 | SMD | −1.54 (−2.56, −0.52) | 0.003 | 60.5 | NA | NA |
| Exercise (continuous MIT) [61] | Katsagoni2016 | IHTG | 2 | 229 | 93 | SMD | −0.86 (−1.36, −0.34) | 0.001 | 63.5 | NA | NA |
| Exercise (low-to-moderate volume MIT) [61] | Katsagoni2016 | IHTG | 4 | 234 | 124 | SMD | −0.50 (−0.77, −0.23) | <0.001 | 0 | NA | NA |
| Exercise (AEx) [62] | Zou2018 | ALT | 20 | 846 | 134 | WMD | −17.04 (−38.08,-4.00) | 0.01 | 0 | NA | 0.04 |
| Exercise (RT) [62] | Zou2018 | ALT | 20 | 846 | 71 | WMD | −17.33 (− 43.90, −8.22) | <0.001 | 7.6 | NA | 0.59 |
| Exercise (AEx + RT) [62] | Zou2018 | ALT | 20 | 846 | 26 | WMD | −32.12 (− 66.11, −1.87) | <0.001 | NA | NA | NA |
| Exercise (AEx) [62] | Zou2018 | AST | 17 | 790 | 110 | WMD | −5.83 (−12.21, −0.45) | <0.001 | 61.6 | NA | 0.03 |
| Exercise (RT) [62] | Zou2018 | AST | 17 | 790 | 60 | WMD | −4.38 (−20.58, 11.83) | <0.001 | 0 | NA | NA |
| Exercise (AEx) [62] | Zou2018 | HOMR-IR | 11 | 492 | 69 | WMD | −0.17 (−0.69, 0.36) | <0.001 | 0 | NA | 0.02 |
| Exercise (RT) [62] | Zou2018 | HOMR-IR | 11 | 492 | 11 | WMD | −1.70 (− 5.61, 2.21) | <0.001 | NA | NA | NA |
| Exercise (AEx + RT) [62] | Zou2018 | HOMR-IR | 11 | 492 | 26 | WMD | −0.52 (−1.51, 0.41) | <0.001 | NA | NA | NA |
| Exercise (AEx) [62] | Zou2018 | BMI | 20 | 13,426 | 846 | WMD | −1.55 (− 3.52, −0.42) | <0.001 | 59.4 | NA | 0.19 |
| Exercise (RT) [62] | Zou2018 | BMI | 20 | 846 | 71 | WMD | −1.81 (−3.80, −0.18) | <0.001 | 0 | NA | 0.07 |
| Exercise (AEx + RT) [62] | Zou2018 | BMI | 20 | 846 | 26 | WMD | −2.09 (−4.07, −0.10) | <0.001 | NA | NA | NA |
| Weight loss [29] | Koutoukidis 2019 | ALT | 21 | 2558 | 1496 | MD | −9.18 (−13.12, −6.50) | <0.001 | 97 | <0.001 | NA |
| Weight loss [29] | Koutoukidis 2019 | AST | 19 | 2558 | 1446 | MD | −4.84 (−7.13, −2.38) | 0.0001 | 96 | <0.00001 | NA |
| Weight loss [29] | Koutoukidis 2019 | GGT | 9 | 1774 | 1124 | MD | −4.35 (−7.67, −1.04) | 0.01 | 96 | <0.00001 | NA |
| Weight loss [29] | Koutoukidis 2019 | Liver stiffness | 4 | 271 | 151 | SMD | −1.11 (−1.91, −0.32) | 0.006 | 94 | <0.00001 | NA |
| Weight loss [29] | Koutoukidis 2019 | Liver steatosis | 11 | 765 | 405 | SMD | −1.48 (−2.27, −0.7) | <0.001 | 94 | <0.01 | NA |
| Weight loss [29] | Koutoukidis 2019 | NAS | 5 | 164 | 93 | SMD | −0.92 (−1.75, −0.09) | 0.03 | 95 | <0.001 | NA |
NAFLD Nonalcoholic fatty liver disease, IHCL Intrahepatocellular lipids, WHR Waist-tohip ratio, WC Waist circumference, BMI Body mass index, Omega-3 PUFAs Omega-3 Polyunsaturated fatty acids, NASH Non-alcoholic steatohepatitis, NAS Nonalcoholic activity score, ALT Alanine aminotransferase, AST Aspartate aminotransferase, TG Triglyceride, TC Total cholesterol, LDL-C Low-density lipoprotein cholesterol, BMI Body mass index, IHLC Intrahepatic lipid content, GGT G-glutamyl transferase, HOMA-IR Homeostasis model assessment of insulin resistance, HDL-C High density lipoprotein, AEx Aerobic exercise training, RT Resistance training, MIT Moderate-intensity, HIT High-intensity training, HIIT High-intensity interval training, IHTG Intrahepatic triglyceride, MIT Moderate inten-sity, ALP Alkaline phosphatase, MD Mean difference, SMD Standardized mean difference, WMD Weighted mean difference, ES Effect size, OR Odds ratio, RR Relative risk, CI Confidence interval, NA Not available