Literature search and study characteristics
Figure 1 shows the details of the literature search and study selection. Our search strategy initially identified 404 papers. Duplicate removal and screening through article title and abstract review identified 28 studies. Seventeen studies were excluded after the full text was reviewed. Finally, 11 studies involving 1000 participants were included in the meta-analysis [8–9, 12–20]. Among them, two studies [16, ][20]had more than one intervention group, therefore each intervention type was compared with the control group and analyzed. Table 1 outlines the characteristics of the included studies. The majority of the included studies reported both male and female patients with NAFLD; only one involved only male patients [18]. All studies involved adult patients. The intervention duration was 8–48 weeks, with a median duration of 16 weeks (4 months).
Methodological quality
Figure 2 presents the methodological quality of the included studies. Most studies had low risk of bias in random sequence generation and allocation concealment; however, three studies had high risk in blinding of participants and personnel and only one study reported the use of blinding in outcome assessment. All studies had low risk of bias in incomplete outcome data and selective reporting.
Effect of physical activity on hepatic enzyme parameters
Eleven, ten, and eight studies reported data for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT), respectively. The combined results suggested that physical activity alone could significantly improve the three hepatic enzymes: ALT (SMD: –0.17, 95% CI: –0.29 to –0.05), AST (SMD: –0.25, 95% CI: –0.37, –0.13), GGT (SMD: –0.21, 95% CI: –0.35, –0.08), and heterogeneity among the studies was not significant (I2 < 50%). However, the effect size was generally small, with a marginal CI (Fig. 3).
Compared with no physical activity, subgroup analysis showed that aerobic exercise alone could significantly reduce AST (SMD: –0.26, 95% CI: –0.43, –0.10), but the effect size was small. However, aerobic exercise alone did not improve ALT and GGT. Resistance exercise alone had similar small improvement effects on the two enzymes: AST (SMD: –0.23, 95% CI: –0.43, –0.03), GGT (SMD: –0.24, 95% CI: –0.44, –0.03). However, the results regarding the combination of aerobic and resistance exercise showed no improvements for all three parameters. Heterogeneity between the subgroups was not significant (ALT, P = 0.39; AST, P = 0.14; GGT, P = 0.93) (Fig. 3).
Subgroup analysis according to intervention duration showed that, regardless of the type of physical activity, sustaining regular physical activity for >4 months could significantly improve hepatic enzyme levels, while <4 months’ physical activity had no significant effect (Fig. 4).
Effect of physical activity on serum lipid parameters
Ten, nine, seven, and nine studies had sufficient data for inclusion in meta-analyses of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), respectively. There was no significant heterogeneity among these studies for these four parameters (I2 < 50%). The pooled result showed that, compared with the control group, participants with regular physical activity were more likely to have slightly lower TC (SMD: –0.22, 95% CI: –0.34, –0.09), TG (SMD: –0.20, 95% CI: –0.32, –0.07), and LDL-C (SMD: –0.26, 95% CI: –0.39, –0.13). Physical activity tended to increase HDL-C levels as compared with the control, but the effect was not significant (SMD: 0.07, 95% CI: –0.06, 0.19) (Fig. 5).
In the subgroup analysis, resistance exercise alone could significantly reduce TC, but with a small effect size (SMD = –0.31, 95% CI: –0.51, –0.10), while neither aerobic exercise alone nor its combination with resistance exercise could improve TC. Heterogeneity between the subgroups was not significant (P = 0.81). Both resistance exercise alone and its combination with aerobic exercise could significantly reduce TG levels, with small (SMD: –0.32, 95% CI: –0.52 to –0.11) and moderate (SMD: –0.59, 95% CI: –1.06 to –0.12) effect size, respectively. However, aerobic exercise alone did not improve TG. There was no significant heterogeneity between the subgroups for TG (P = 0.10). The subgroup analyses also suggested that aerobic exercise alone and resistance exercise alone can significantly reduce LDL-C levels (SMD: –0.21, 95% CI: –0.37 to –0.04; SMD: –0.35, 95% CI: –0.56 to –0.15, respectively), but the combination of aerobic and resistance exercise had no significant effect on LDL-C, which may due to the small sample size, as only one study was included in this subgroup. Heterogeneity between the subgroups was not significant (P = 0.66). All three subgroups showed non-significant results for HDL-C, and there was no difference between the subgroups (P = 0.94) (Fig. 5).
For duration of physical activity, both the ≥4 months and <4 months groups had a significant effect on TC regardless of the type of physical activity (≥4 months, SMD: –0.19, 95% CI –0.32 to –0.06; <4 months, SMD: –0.40, 95% CI –0.78 to –0.02). Similarly, both the ≥4 months and <4 months groups had a significant effect on TG regardless of the type of physical activity (≥4 months, SMD: –0.16, 95% CI –0.30 to –0.03; <4 months, SMD: –0.48, 95% CI –0.86 to –0.10). However, LDL-C reduction was significant only in the ≥4 months group (SMD: –0.25, 95% CI: –0.38 to –0.12). Both subgroups showed a non-significant effect for HDL-C (Fig. 6).
Effect of physical activity on glucose metabolism parameters
Nine, six, and six studies had sufficient data for inclusion in analyses of fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR), respectively. Heterogeneity among the studies for these three glucose metabolism parameters was not significant (I2 < 50%). The fixed-effect model showed that physical activity could reduce fasting glucose (SMD: –0.25, 95% CI: –0.37 to –0.12) and HOMA-IR (SMD: –0.38, 95% CI: –0.52, –0.24). However, physical activity had no significant effect in improving fasting insulin (SMD: –0.18, 95% CI: –0.45, 0.10) (Fig. 7).
In the subgroup analysis, compared with the control, both aerobic exercise alone and resistance exercise alone could significantly reduce fasting glucose (aerobic exercise alone, SMD: –0.26, 95% CI: –0.43 to –0.10; resistance exercise alone, SMD: –0.27, 95% CI: –0.47 to –0.06) and HOMA-IR (aerobic exercise alone, SMD: –0.42, 95% CI: –0.63 to –0.22; resistance exercise alone, SMD: –0.34, 95% CI: –0.54 to –0.13), but the two exercise types combined could not improve these two parameters. Heterogeneity between both subgroups for fasting glucose and HOMA-IR was not significant (P = 0.07 and P = 0.11 respectively). As for fasting insulin, the difference between subgroups was not significant (Fig. 7).
In the subgroup analysis according to intervention duration, significant improvements were found in the ≥4 months groups for fasting glucose and HOMA-IR. There was no significant effect for subgroup <4 months on all three parameters (Fig. 8).
Sensitivity analysis and publication bias
Sensitivity analysis showed that the study by Jia et al. [20]could possibly influence the pooled results for fasting insulin and HOMA-IR. After excluding it, the pooled results for fasting insulin became significant (SMD: –0.36, 95% CI: –0.69 to –0.02) and that for HOMA-IR became non-significant (SMD: –0.18, 95% CI: –0.39, 0.02), while the results for the other parameters were unlikely to be substantially altered.
Publication bias analysis was conducted when there were more than 10 included studies. Egger’s test indicated statistically significant publication bias among the studies for ALT (P = 0.043).
Adverse events
Three studies [14, 19-] [19] [20]mentioned adverse events during the physical activity intervention. Among 1000 participants, two had knee pain, one had shoulder pain, one had back pain, and two had bone fractures that did not occur during the exercise sessions reported. Overall, the incidence of adverse events was quite low, suggesting that physical activity intervention was well-tolerated. However, only a few studies reported on adverse events, and the trials lasted 2–13 months. Therefore, further studies are needed to prove the long-term safety of physical activity intervention.