Telemonitoring-Supported Exercise Training in Employees With Metabolic Syndrome Improves Liver Inflammation and Fibrosis

Sven Haufe, Katharina L Hupa-Breier, Pauline Bayerle, Hedwig T Boeck, Simone Rolff, Thorben Sundermeier, Arno Kerling, Julian Eigendorf, Momme Kück, Alexander A Hanke, Ralf Ensslen, Lars Nachbar, Dirk Lauenstein, Dietmar Böthig, Denise Hilfiker-Kleiner, Meike Stiesch, Christoph Terkamp, Heiner Wedemeyer, Axel Haverich, Uwe Tegtbur, Sven Haufe, Katharina L Hupa-Breier, Pauline Bayerle, Hedwig T Boeck, Simone Rolff, Thorben Sundermeier, Arno Kerling, Julian Eigendorf, Momme Kück, Alexander A Hanke, Ralf Ensslen, Lars Nachbar, Dirk Lauenstein, Dietmar Böthig, Denise Hilfiker-Kleiner, Meike Stiesch, Christoph Terkamp, Heiner Wedemeyer, Axel Haverich, Uwe Tegtbur

Abstract

Introduction: Metabolic syndrome (MetS) is a major health problem worldwide and the main risk factor for metabolic-associated fatty liver disease (MAFLD). Established treatment options are lifestyle interventions facilitating dietary change and increased physical activity. Here, we tested the effect of a telemonitoring-supported intervention on liver parameter of inflammation and fibrosis in individuals with MetS.

Methods: This was a prospective, randomized, parallel-group, and assessor-blind study performed in workers of the main Volkswagen factory (Wolfsburg, Germany). Volunteers with diagnosed MetS were randomly assigned (1:1) to a 6-month lifestyle intervention focusing on supervised, activity-tracker-guided exercise or to a waiting-list control group. This secondary analysis assessed the effect of the intervention on liver enzymes and MAFLD-related parameters.

Results: We screened 543 individuals between October 10, 2017, and February 27, 2018, of whom 314 were randomly assigned to the intervention group (n = 160) or control group (n = 154). Liver transaminases, alkaline phosphatase, and gamma-glutamyl transferase significantly decreased after 6 months in the intervention group compared with the CG. Furthermore, an aspartate aminotransferase-to-platelet ratio index score as a marker for liver fibrosis significantly decreased in the intervention group. These improvements were associated with changes in obesity and exercise capacity.

Discussion: A 6-month lifestyle intervention based on exercise training with individualized telemonitoring-based supervision led to improvements of liver inflammation and fibrosis in employees with MetS. Therefore, this intervention shows therapeutic potential for individuals at high risk of MAFLD (ClinicalTrials.gov Identifier: NCT03293264).

Conflict of interest statement

Guarantor of the article: Uwe Tegtbur.

Specific author contributions: Sven Haufe and Katharina Luise Hupa-Breier contributed equally to this work. Study concept and design: U.T., D.H.-K., M.S., C.T., D.H.-K., and A.H. Administrative support: U.T., L.N., and D.L. Performed experiment: P.B., H.T.B., S.R., T.S., A.K., J.E., M.K., A.A.H., and R.E. Analysis and interpretation of data: S.H., K.L.H.-B., and H.W. Statistical analysis: S.H. and D.B. Manuscript writing: S.H. and K.L.H.-B. Obtained funding: U.T. and A.H. All authors approved the final version of the manuscript.

Financial support: This study was supported and funded by grants from Audi BKK health insurance and the German Research Foundation through the Cluster of Excellence “REBIRTH.” The work of K.H.-B. was supported by PRACTIS–Clinician Scientist Program of Hannover Medical School, funded by the German Research Foundation (DFG, ME 3696/3-1, RAW).

Potential competing interests: H.W. received lecture fees from Falk Pharma, Gore, Merz, and Norgine and acts as a principal investigator for Falk Pharma. He received grants from Merz and Norgine. K.H.-B. received lecture fees from Falk Pharma and Gilead. These activities do not relate to the current manuscript which was performed without any support from the above mentioned companies. All other authors declare no conflicts of interest.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.

Figures

Figure 1.
Figure 1.
Participant flow chart.
Figure 2.
Figure 2.
(a) Liver transaminases and (b) liver enzymes before and after the intervention. *Significant within groups from before to after the intervention. Data are mean ± SEM. ALT, alanine aminotransferase; AP, alkaline phosphatase; AST = aspartate aminotransferase; gGT = gamma-glutamyl transferases.
Figure 3.
Figure 3.
Percentage of patients with elevated ALT levels at baseline, who could achieve normalization of ALT levels at the end of treatment according to the local reference values (female: 34 IU/L; male: 45 IU/L) and in accordance to the AASLD recommendation (female: 19 IU/L; male: 30 IU/L). Data are mean ± SEM. AASLD, American Association for the Study of Liver Diseases; ALT, alanine aminotransferase.
Figure 4.
Figure 4.
(a) The calculated APRI score before and after the intervention. (b) Subgroup of patients without fibrosis (APRI score <0.5) and with possible fibrosis (APRI score: >0.5 < 1.5) before and after the intervention. *Significant within groups from before to after the intervention. Data are mean ± SEM. APRI, aspartate aminotransferase-to-platelet ratio index.
Figure 5.
Figure 5.
Change in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) according to change in exercise capacity or change in body mass index (BMI). The framed P values are given for differences across tertiles as analyzed with a 1-way ANOVA. *Different to low tertile with P < 0.01 as analyzed with Bonferroni post hoc tests. Data are mean ± SEM.

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