Aerobic Exercise Training in Patients With Chronic Hepatitis B and Hepatic Steatosis (FitLiver)

Effect of Aerobic Exercise Training on Fat-fraction of the Liver in Patients With Chronic Hepatitis B and Hepatic Steatosis: a Randomised Controlled Intervention Trial. The Fit Liver Study

This study is a randomised, controlled, unblinded, clinical intervention trial consisting of 12 weeks of aerobic exercise training. Thirty persons with chronic hepatitis B (CHB) and hepatic steatosis are randomised to either aerobic exercise training (intervention group, n=15) or no intervention (control group, n=15). The study will investigate the effects of the exercise intervention on the liver and the hypothesis is that the exercise group will reduce the fat-fraction of the liver after the intervention.

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic; Hepatic Steatosis
• Intervention / Treatment: Behavioral: High Intensity Interval Training

Detailed Description

Primary aim: To investigate whether regular aerobic exercise training will decrease the fat-fraction of the liver in persons with CHB and hepatic steatosis shown by magnetic resonance imaging (MRI) by use of Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL-IQ).

Secondary aim: To investigate the effects of aerobic exercise training on hepatokine secretion in persons with CHB and hepatic steatosis. Also, to investigate if regular physical exercise will improve lipid- and glucose metabolism, liver status, markers of inflammation, body composition, and blood pressure.

Study participants will undergo pre and post the interventioon: Clinical examination with ECG, blood pressure measurements, blood sampling, oral glucose tolerance test, a hormone infusion of somatostatin and glucagon, -increasing the glucagon/insulin ratio mimicking an acute exercise bout, measuring the effect on circulating hepatokines and cytokines, fibroscan, VO2-max test, DXA scan, AX3 activity monitoring, nail fold capillaryscopy, IQOLA SF-36 and IPAQ-SF questionnaire, 24H food intake registration, MRI scan of the liver and optional liver biopsy. 6 and 12 months follow-up is planned.

The exercise intervention will be randomised 1:1 with no stratification: The training program includes three weekly supervised training sessions of 40 minutes/session over 12 weeks. Participants are instructed not to change their lifestyles during the intervention.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Centre for Physical Activity Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Chronic hepatitis B defined by HBsAg positive >6 months
• Positive HBV-DNA
• Age >30
• Hepatic steatosis diagnosed by Controlled Attenuated Parameter (CAP) >250 assessed by Transient Elastography or by ultrasound defined hepatic steatosis

Exclusion Criteria:

• HIV, HCV, HDV-co infection
• Primary biliary cholangitis
• Wilsons Disease
• Autoimmune hepatitis
• Hepatocellular carcinoma
• Antiviral medication
• Steatogenic medication (systemic corticosteroids, amiodarone, tamoxifen, valproic acid, and methotrexate)
• Average alcohol intake >30 g for men and >20 g for women pr. day
• Contraindications for MRI scan
• Coronary artery disease contraindicating HIIT
• Unable to understand and read written information for participants written consent
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No Intervention; No lifestyle changes
Experimental: Exercise Intervention Arm; Three high intensity interval exercise sessions per week of 40 minutes duration per session. Exercise will be performed on ergometerbikes.	Behavioral: High Intensity Interval Training; A training session consists of 40 minutes as follows: 4x4 minutes at > 85% of heart rate maximum (HRmax) alternated by 3x3 minutes active recovery at (50-70% of HRmax) and a 10-min-warm-up (60-79% of HRmax) and 5- minute cool-down at ~ warm up intensity. HRmax was determined during the VO2max test at baseline visit. Minutes spent in the different heart rate zones is monitored during the session (zone 1: 60-69%, zone 2: 70-74%, zone 3: 75-79%, zone 4: 80-84%, zone 5: >85% of HRmax).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fat-Fraction of the Liver	Hepatic fat-fraction measured by MRI with IDEAL-IQ (%)	From baseline to follow-up at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibroblast growth factor 21 (FGF21) secretion	FGF21 (ng/L) secretion during a hormone infusion of somatostatin and glucagon	From baseline to follow-up at 12 weeks
Follistatin secretion	Follistatin (ng/L) secretion during a hormone infusion of somatostatin and glucagon	From baseline to follow-up at 12 weeks
Growth/differentiation factor 15 (GDF15) secretion	GDF15 (ng/L) secretion during a hormone infusion of somatostatin and glucagon	From baseline to follow-up at 12 weeks
Angiopoietin-like 4 (ANGPTL4) secretion	ANGPTL4 (μg/L) secretion during a hormone infusion of somatostatin and glucagon	From baseline to follow-up at 12 weeks
C-reactive protein (CRP) secretion	CRP (mg/L) secretion during a hormone infusion of somatostatin and glucagon	From baseline to follow-up at 12 weeks
Interferon-ϒ secretion	Interferon-ϒ (pg/mL) secretion during a hormone infusion of somatostatin and glucagon	From baseline to follow-up at 12 weeks
Interleukin-10 secretion	Interleukin-10 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon	From baseline to follow-up at 12 weeks
Interleukin-8 secretion	Interleukin-8 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon	From baseline to follow-up at 12 weeks
Interleukin-6 secretion	Interleukin-6 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon	From baseline to follow-up at 12 weeks
Interleukin-1 secretion	Interleukin-1 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon	From baseline to follow-up at 12 weeks
TNFα secretion	TNFα (pg/mL) secretion during a hormone infusion of somatostatin and glucagon	From baseline to follow-up at 12 weeks
Visceral fat	Visceral fat assessed by MRI (kg)	From baseline to follow-up at 12 weeks
Total fat mass	Total fat mass assessed by DXA scan (kg)	From baseline to follow-up at 12 weeks
Total free fat mass	Total free fat mass assessed by DXA scan (kg)	From baseline to follow-up at 12 weeks
Total lean body mass	Total lean body mass assessed by DXA scan (kg)	From baseline to follow-up at 12 weeks
Body weight	Body weight (kg)	From baseline to follow-up at 12 weeks
Blood pressure measurements	Systolic blood pressure (mmHg) and diastolic blood pressure (mmHg)	From baseline to follow-up at 12 weeks
Physical fitness (VO2max)	Physical fitness assessed by VO2max (mL/kg/min)	From baseline to follow-up at 12 weeks
Total physical activity	Total physical activity assessed by activity monitor (hours, minutes)	From baseline, at 6 weeks to follow-up at 12 weeks
Moderate and vigorous physical activity (MVPA)	Moderate and vigorous physical activity (MVPA) activity monitor (hours, minutes)	From baseline, at 6 weeks to follow-up at 12 weeks
Sedentary time (SED)	Sedentary time (SED) activity monitor (hours, minutes)	From baseline, at 6 weeks to follow-up at 12 weeks
Hepatitis B virus (DNA)	Hepatitis B virus (DNA) (IU/mL)	From baseline to follow-up at 12 weeks
Oral glucose tolerance test	Oral glucose tolerance test (mmol/L)	From baseline to follow-up at 12 weeks
Glycated haemoglobin type 1AC (HbA1c)	Glycated haemoglobin type 1AC (HbA1c) (mmol/mL)	From baseline to follow-up at 12 weeks
Fasting glucose	Fasting glucose (mmol/L)	From baseline to follow-up at 12 weeks
Fasting Insulin	Fasting Insulin (pmol/L)	From baseline to follow-up at 12 weeks
Lipid measurements	Total cholesterol (mmol/L), total triglyceride (mmol/L), low density lipoprotein (LDL) (mmol/L), high density lipoprotein (HDL) (mmol/L)	From baseline to follow-up at 12 weeks
Alanine transaminase (ALT)	Alanine transaminase (ALT) (U/L)	From baseline to follow-up at 12 weeks
Aspartate transaminase (AST)	Aspartate transaminase (AST) (U/L)	From baseline to follow-up at 12 weeks
Fibrosis-4 (FIB-4)	Fibrosis-4 (FIB-4)	From baseline to follow-up at 12 weeks
International Normalised Ratio (INR)	International Normalised Ratio (INR)	From baseline to follow-up at 12 weeks

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Copenhagen University Hospital, Hvidovre

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2022
• Primary Completion (Actual): September 30, 2023
• Study Completion (Actual): October 1, 2023

Study Registration Dates

• First Submitted: February 11, 2022
• First Submitted That Met QC Criteria: February 22, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Fatty Liver; Hepatitis B, Chronic
• Other Study ID Numbers: H-21034236

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: If the data can be fully anonymized then the data can be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No