Hepatic Steatosis, Hepatitis B, Chronic
Conditions
Brief summary
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.
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.
Interventions
BEHAVIORALHigh 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).
Sponsors
Copenhagen University Hospital, Hvidovre
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fat-Fraction of the Liver | From baseline to follow-up at 12 weeks | Hepatic fat-fraction measured by MRI with IDEAL-IQ (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fibroblast growth factor 21 (FGF21) secretion | From baseline to follow-up at 12 weeks | FGF21 (ng/L) secretion during a hormone infusion of somatostatin and glucagon |
| Follistatin secretion | From baseline to follow-up at 12 weeks | Follistatin (ng/L) secretion during a hormone infusion of somatostatin and glucagon |
| Growth/differentiation factor 15 (GDF15) secretion | From baseline to follow-up at 12 weeks | GDF15 (ng/L) secretion during a hormone infusion of somatostatin and glucagon |
| Angiopoietin-like 4 (ANGPTL4) secretion | From baseline to follow-up at 12 weeks | ANGPTL4 (μg/L) secretion during a hormone infusion of somatostatin and glucagon |
| C-reactive protein (CRP) secretion | From baseline to follow-up at 12 weeks | CRP (mg/L) secretion during a hormone infusion of somatostatin and glucagon |
| Interferon-ϒ secretion | From baseline to follow-up at 12 weeks | Interferon-ϒ (pg/mL) secretion during a hormone infusion of somatostatin and glucagon |
| Interleukin-10 secretion | From baseline to follow-up at 12 weeks | Interleukin-10 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon |
| Interleukin-8 secretion | From baseline to follow-up at 12 weeks | Interleukin-8 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon |
| Interleukin-6 secretion | From baseline to follow-up at 12 weeks | Interleukin-6 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon |
| Interleukin-1 secretion | From baseline to follow-up at 12 weeks | Interleukin-1 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon |
| TNFα secretion | From baseline to follow-up at 12 weeks | TNFα (pg/mL) secretion during a hormone infusion of somatostatin and glucagon |
| Visceral fat | From baseline to follow-up at 12 weeks | Visceral fat assessed by MRI (kg) |
| Total fat mass | From baseline to follow-up at 12 weeks | Total fat mass assessed by DXA scan (kg) |
| Total free fat mass | From baseline to follow-up at 12 weeks | Total free fat mass assessed by DXA scan (kg) |
| Total lean body mass | From baseline to follow-up at 12 weeks | Total lean body mass assessed by DXA scan (kg) |
| Fasting Insulin | From baseline to follow-up at 12 weeks | Fasting Insulin (pmol/L) |
| Blood pressure measurements | From baseline to follow-up at 12 weeks | Systolic blood pressure (mmHg) and diastolic blood pressure (mmHg) |
| Physical fitness (VO2max) | From baseline to follow-up at 12 weeks | Physical fitness assessed by VO2max (mL/kg/min) |
| Total physical activity | From baseline, at 6 weeks to follow-up at 12 weeks | Total physical activity assessed by activity monitor (hours, minutes) |
| Moderate and vigorous physical activity (MVPA) | From baseline, at 6 weeks to follow-up at 12 weeks | Moderate and vigorous physical activity (MVPA) activity monitor (hours, minutes) |
| Sedentary time (SED) | From baseline, at 6 weeks to follow-up at 12 weeks | Sedentary time (SED) activity monitor (hours, minutes) |
| Hepatitis B virus (DNA) | From baseline to follow-up at 12 weeks | Hepatitis B virus (DNA) (IU/mL) |
| Oral glucose tolerance test | From baseline to follow-up at 12 weeks | Oral glucose tolerance test (mmol/L) |
| Glycated haemoglobin type 1AC (HbA1c) | From baseline to follow-up at 12 weeks | Glycated haemoglobin type 1AC (HbA1c) (mmol/mL) |
| Fasting glucose | From baseline to follow-up at 12 weeks | Fasting glucose (mmol/L) |
| Lipid measurements | From baseline to follow-up at 12 weeks | Total cholesterol (mmol/L), total triglyceride (mmol/L), low density lipoprotein (LDL) (mmol/L), high density lipoprotein (HDL) (mmol/L) |
| Alanine transaminase (ALT) | From baseline to follow-up at 12 weeks | Alanine transaminase (ALT) (U/L) |
| Aspartate transaminase (AST) | From baseline to follow-up at 12 weeks | Aspartate transaminase (AST) (U/L) |
| Fibrosis-4 (FIB-4) | From baseline to follow-up at 12 weeks | Fibrosis-4 (FIB-4) |
| International Normalised Ratio (INR) | From baseline to follow-up at 12 weeks | International Normalised Ratio (INR) |
| Body weight | From baseline to follow-up at 12 weeks | Body weight (kg) |
Countries
Denmark
Outcome results
None listed