Does aerobic exercise reduce NASH and liver fibrosis in patients with non-alcoholic fatty liver disease? A systematic literature review and meta-analysis

Abstract

BackgroundExercise is an effective strategy for the prevention and regression of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD), but it is unclear whether it can reduce advanced stages of NAFLD, i.e., steatohepatitis and liver fibrosis. Furthermore, it is not evident which modality of exercise is optimal to improve/attenuate NAFLD.ObjectivesThe aim is to systematically review evidence for the effect of aerobic exercise (AE) on NAFLD, in particular non-alcoholic steatohepatitis (NASH) and liver fibrosis.MethodsA systematic literature search was conducted in Medline and Embase. Studies were screened and included according to predefined criteria, data were extracted, and the quality was assessed by Cochrane risk of bias tools by two researchers independently according to the protocol registered in the PROSPERO database (CRD42021270059). Meta-analyses were performed using a bivariate random-effects model when there were at least three randomized intervention studies (RCTs) with similar intervention modalities and outcome.ResultsThe systematic review process resulted in an inclusion a total of 24 studies, 18 RCTs and six non-RCTs, encompassing 1014 patients with NAFLD diagnosed by histological or radiological findings. Studies were grouped based on the type of AE: moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT). A total of twelve meta-analyses were conducted. Compared to controls, MICT resulted in a mean difference (MD) in the NAFLD biomarkers alanine transaminase (ALT) and aspartate aminotransferase (AST) of -3.59 (CI: -5.60, -1.59, p<0.001) and -4.05 (CI: -6.39, -1.71, p<0.001), respectively. HIIT resulted in a MD of -4.31 (95% CI: -9.03, 0.41, p=0.07) and 1.02 (95% CI: -6.91, 8.94, p=0.8) for ALT and AST, respectively. Moreover, both AE types compared to controls showed a significantly lower magnetic resonance spectroscopy (MRS) determined liver fat with a MD of -5.19 (95% CI: -7.33, -3.04, p<0.001) and -3.41 (95% CI: -4.74, -2.08, p<0.001), for MICT and HIIT respectively. MICT compared to controls resulted in a significantly higher cardiorespiratory fitness (MD: 4.43, 95% CI: 0.31, 8.55, p=0.03).ConclusionLiver fat is decreased by AE with a concomitant decrease of liver enzymes. AE improved cardiorespiratory fitness. Further studies are needed to elucidate the impact of different types of AE on hepatic inflammation and fibrosis.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier (CRD42021270059).

Effect of exercise intervention on clinical parameters in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a meta-analysis of randomized controlled trials

“…HDL-C levels were elevated in the MICT group, while changes were NS in the HIIT and RT groups. Our results contradict the conclusions of some previous studies; Houttu’s meta-analysis showed that HIIT reduced plasma TG concentrations, while MICT reduced TC and LDL-C levels [25], and Babu’s meta-analysis showed that RT was effective in improving TG levels [10]. The results that caused the variability of each other’s meta-analysis may be that some of the patients included in the study had lipid levels within the normal range before and after the intervention, such as in Cassidy’s and Bacchi’s studies [14,19], and the differences in the included studies may affect the conclusions of the meta-analysis.…”

“…However, subgroup analysis demonstrated that the RT group did not significantly affect HbA1c or HOMA-IR. These findings aligned with previous research, as the meta-analysis by Ye et al also found no significant effect of RT on HbA1c [31], and the meta-analysis by Houttu et al showed a decrease in HOMA-IR in the HIIT group [25]. However, a study by Church et al reported that the combination of RT and aerobic training significantly reduced HbA1c levels [32], and a study by Yavari et al found that both aerobic and RT improved glycemia, but RT had less improvement than aerobic training.…”

“…also found no significant effect of RT on HbA1c [31], and the meta-analysis by Houttu et al . showed a decrease in HOMA-IR in the HIIT group [25]. However, a study by Church et al .…”

“…Several meta-analyses have shown that lifestyle changes such as dietary control and/or exercise can improve several indices and alleviate various complications in patients with NAFLD [10,24–27]. This meta-analysis of our study analyzed the effects of different exercise regimens on clinical parameters such as liver enzymes, lipids, and glucose metabolism in patients with NAFLD combined with T2DM.…”

Effects of short‐term supervised exercise training on liver fat in adolescents with obesity: a randomized controlled trial

“…HIIT, defined as alternating cycles of short periods of intense aerobic and anaerobic exercise at near‐maximum capacity, has been suggested as a time‐efficient and effective exercise modality in MASLD treatment [15,27]. Many different HIIT protocols with varying workout times have been described, but available literature does not support superiority of one protocol over the others; HIIT was shown to improve CRF in healthy adolescents with obesity regardless of body composition, and the effects of prolonged high‐volume versus short‐term low‐volume HIIT programs were comparably effective [28].…”