Research output: Contribution to journal › Review article › Academic › peer-review
Does aerobic exercise reduce NASH and liver fibrosis in patients with non-alcoholic fatty liver disease? A systematic literature review and meta-analysis. / Houttu, Veera; Bouts, Julia; Vali, Yasaman et al.
In: Frontiers in endocrinology, Vol. 13, 1032164, 03.11.2022.Research output: Contribution to journal › Review article › Academic › peer-review
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TY - JOUR
T1 - Does aerobic exercise reduce NASH and liver fibrosis in patients with non-alcoholic fatty liver disease? A systematic literature review and meta-analysis
AU - Houttu, Veera
AU - Bouts, Julia
AU - Vali, Yasaman
AU - Daams, Joost
AU - Grefhorst, Aldo
AU - Nieuwdorp, Max
AU - Holleboom, Adriaan G.
N1 - Funding Information: This work has received funding from an ITN Marie Curie BestTreat – Building a Gut Microbiome Engineering Toolbox for In-Situ Therapeutic Treatments for Non-alcoholic Fatty Liver Disease No. 813781 ITN BestTreat (on which VH is appointed). AH was supported by the Amsterdam UMC Fellowship, Health–Holland TKI-PPP grants, grants for the Dutch Gastroenterology Foundation and by a research grant from Novo Nordisk. MN was supported by a personal ZONMW VICI grant 2020 [09150182010020]. Publisher Copyright: Copyright © 2022 Houttu, Bouts, Vali, Daams, Grefhorst, Nieuwdorp and Holleboom.
PY - 2022/11/3
Y1 - 2022/11/3
N2 - Background: Exercise 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. Objectives: The aim is to systematically review evidence for the effect of aerobic exercise (AE) on NAFLD, in particular non-alcoholic steatohepatitis (NASH) and liver fibrosis. Methods: A 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. Results: The 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). Conclusion: Liver 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 Registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42021270059).
AB - Background: Exercise 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. Objectives: The aim is to systematically review evidence for the effect of aerobic exercise (AE) on NAFLD, in particular non-alcoholic steatohepatitis (NASH) and liver fibrosis. Methods: A 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. Results: The 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). Conclusion: Liver 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 Registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42021270059).
KW - aerobic exercise
KW - high-intensity interval training
KW - meta-analysis
KW - moderate-intensity continuous training
KW - non-alcoholic fatty liver disease
KW - systematic review
UR - http://www.scopus.com/inward/record.url?scp=85142186705&partnerID=8YFLogxK
U2 - 10.3389/fendo.2022.1032164
DO - 10.3389/fendo.2022.1032164
M3 - Review article
C2 - 36407307
VL - 13
JO - Frontiers in endocrinology
JF - Frontiers in endocrinology
SN - 1664-2392
M1 - 1032164
ER -
ID: 27505652