Effect of High Intensity Exercise Rehabilitation on Liver Function and Insulin Sensitivity in Patients With MASLD

University Ghent92 enrolled

Overview

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, and is associated with obesity and the metabolic syndrome. Physical activity and lifestyle interventions are among the most recommended treatments for individuals with MASLD. In this RCT, we will evaluate the effect of combined exercise training "strength and aerobic training" versus "strength and high intensity training (HIIT)". The main outcome parameter is the severity of liver steatosis. Patients will be recruited at the fatty liver clinic of the UZ Gent.

Physical activity and lifestyle interventions, including exercise, are recommended for individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). Weight loss has been found to improve MASLD histologically, but exercise alone can also reduce liver fat accumulation, even without significant weight loss. Exercise has positive effects on chronic inflammation, type 2 diabetes mellitus (T2DM), and mitochondrial function in MASLD patients. Studies suggest that both aerobic and resistance exercise are effective in reducing fat content and liver enzyme levels in MASLD, and thereby generate positive effects on insulin sensitivity and cardiovascular risk. The potential of high-intensity interval training (HIIT) is large in various settings, but was never explored in this population. Moreover, the combination with strength training can have additional health effects which remain to be explored. All subjects are recruited in the liver steatosis outpatient clinic of the university hospital in Ghent by the physicians and researchers of this study. After patient selection and obtaining informed consent, they will be screened in the rehabilitation center for cardiorespiratory fitness.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Interventions

Combined aerobic + strength trainingOTHER

Participants will follow a combination of endurance and strength training for 14 weeks. There will be three sessions every week: two at Ghent university department of rehabilitation and one at home. Each session will last approximately one hour.

Combined strength + HIIT trainingOTHER

6 weeks of endurance training and strength training, 8 weeks of strength training and HIIT. Participants will follow the same combination of endurance and strength training for the first six weeks, to build up to a baseline level of physical fitness. They will then switch to eight weeks of a combination of strength training and High Intensity Interval Training (HIIT). There will be three sessions every week: two at Ghent university department of rehabilitation and one at home. Each session will last approximately one hour.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosed with MASLD by ultrasound, CAP and/or biopsy * Age between 18 and 75 years old * No significant liver fibrosis (Fibroscan \< 7.5 kPa; if it is between \>7.5 and \<10, there must be absence of liver fibrosis in the biopsy) Exclusion Criteria: * Presence of other liver diseases that may contribute to the clinical presentation in the patient * Severe cardiovascular, orthopedic, physical or other illnesses that make it impossible to participate in the study's exercise rehabilitation program or where safety cannot be guaranteed * Pregnancy * Pharmacological treatment that directly affects MASLD (e.g. GLP-1 analogues) * A change in medication in the last three months before the study that affects metabolic disease stability

Outcomes

Primary Outcomes

Liver steatosis by CAP

Liver stiffness measurement will be performed using vibration-controlled transient elastography, more specifically the Fibroscan. This method measures the fat accumulation in the liver (dB/m) and the level of scar tissue (kPa), represented as the CAP or steatosis score and the fibrosis score respectively.