TY - JOUR

T1 - Effect of aerobic exercise training on the fat fraction of the liver in persons with chronic hepatitis B and hepatic steatosis

T2 - Trial protocol for a randomized controlled intervention trial— The FitLiver study

AU - Jespersen, Sofie

AU - Plomgaard, Peter

AU - Madsbad, Sten

AU - Hansen, Adam Espe

AU - Bandholm, Thomas

AU - Pedersen, Bente Klarlund

AU - Ritz, Christian

AU - Weis, Nina

AU - Krogh-Madsen, Rikke

N1 - Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - Background: The global prevalence of chronic hepatitis B is more than 300 million people, and in Denmark, 17,000 people are estimated to have chronic hepatitis B. Untreated, chronic hepatitis B can lead to the development of liver cirrhosis and liver cancer. There is no curable therapy. In persons with obesity and chronic hepatitis B infection, the development of hepatic steatosis imposes a double burden on the liver, leading to an increased risk of cirrhosis and liver cancer. In patients without chronic hepatitis B, exercise interventions have shown beneficial effects on hepatic steatosis through improvements in fat fraction of the liver, insulin resistance, fatty acid metabolism, and glucose metabolism, as well as activation of liver-induced regulatory protein secretion (hepatokines) after the exercise intervention. Objective: To investigate in persons with chronic hepatitis B and hepatic steatosis: Primary: Whether exercise will decrease the fat fraction of the liver.Secondary: If exercise will affect hepatokine secretion and if it will improve lipid- and glucose metabolism, liver status, markers of inflammation, body composition, and blood pressure. Methods: A randomized, controlled, clinical intervention trial consisting of 12 weeks of aerobic exercise training or no intervention. Thirty persons with chronic hepatitis B and hepatic steatosis will be randomized 1:1. Before and after the intervention, participants will undergo an MRI scan of the liver, blood sampling, oral glucose tolerance test, fibroscan, VO2max test, DXA scan, blood pressure measurements, and optional liver biopsy. Lastly, a hormone infusion test with somatostatin and glucagon to increase the glucagon/insulin ratio for stimulating secretion of circulating hepatokines will be performed. The training program includes three weekly training sessions of 40 min/session over 12 weeks. Discussion: This trial, investigating high-intensity interval training in persons with chronic hepatitis B and hepatic steatosis, is the first exercise intervention trial performed on this group of patients. If exercise reduces hepatic steatosis and induces other beneficial effects of clinical markers in this group of patients, there might be an indication to recommend exercise as part of treatment. Furthermore, the investigation of the effect of exercise on hepatokine secretion will provide more knowledge on the effects of exercise on the liver. Trial registration: Danish Capital Regions committee on health research ethics reference: H-21034236 (version 1.4 date: 19–07-2022) and ClinicalTrials.gov: NCT05265026.

AB - Background: The global prevalence of chronic hepatitis B is more than 300 million people, and in Denmark, 17,000 people are estimated to have chronic hepatitis B. Untreated, chronic hepatitis B can lead to the development of liver cirrhosis and liver cancer. There is no curable therapy. In persons with obesity and chronic hepatitis B infection, the development of hepatic steatosis imposes a double burden on the liver, leading to an increased risk of cirrhosis and liver cancer. In patients without chronic hepatitis B, exercise interventions have shown beneficial effects on hepatic steatosis through improvements in fat fraction of the liver, insulin resistance, fatty acid metabolism, and glucose metabolism, as well as activation of liver-induced regulatory protein secretion (hepatokines) after the exercise intervention. Objective: To investigate in persons with chronic hepatitis B and hepatic steatosis: Primary: Whether exercise will decrease the fat fraction of the liver.Secondary: If exercise will affect hepatokine secretion and if it will improve lipid- and glucose metabolism, liver status, markers of inflammation, body composition, and blood pressure. Methods: A randomized, controlled, clinical intervention trial consisting of 12 weeks of aerobic exercise training or no intervention. Thirty persons with chronic hepatitis B and hepatic steatosis will be randomized 1:1. Before and after the intervention, participants will undergo an MRI scan of the liver, blood sampling, oral glucose tolerance test, fibroscan, VO2max test, DXA scan, blood pressure measurements, and optional liver biopsy. Lastly, a hormone infusion test with somatostatin and glucagon to increase the glucagon/insulin ratio for stimulating secretion of circulating hepatokines will be performed. The training program includes three weekly training sessions of 40 min/session over 12 weeks. Discussion: This trial, investigating high-intensity interval training in persons with chronic hepatitis B and hepatic steatosis, is the first exercise intervention trial performed on this group of patients. If exercise reduces hepatic steatosis and induces other beneficial effects of clinical markers in this group of patients, there might be an indication to recommend exercise as part of treatment. Furthermore, the investigation of the effect of exercise on hepatokine secretion will provide more knowledge on the effects of exercise on the liver. Trial registration: Danish Capital Regions committee on health research ethics reference: H-21034236 (version 1.4 date: 19–07-2022) and ClinicalTrials.gov: NCT05265026.

KW - Exercise

KW - Fatty liver

KW - Hepatitis B

KW - High-intensity interval training

KW - Magnetic resonance imaging

KW - Randomized controlled trial

U2 - 10.1186/s13063-023-07385-y

DO - 10.1186/s13063-023-07385-y

M3 - Journal article

C2 - 37312098

AN - SCOPUS:85161893163

VL - 24

JO - Trials

JF - Trials

SN - 1745-6215

IS - 1

M1 - 398

ER -