Gastroenterology · Medical Literature
Effect of high-intensity interval training in patients with chronic hepatitis B and hepatic steatosis: A randomised controlled trial.
Abstract
Having both chronic hepatitis B and hepatic steatosis increases the risk of liver-related morbidity and mortality. We aimed to investigate if high-intensity interval training could decrease the liver fat-fraction and improve liver status, body composition, lipid- and glucose metabolism, and blood pressure in patients with chronic hepatitis B and hepatic steatosis. In a randomised, controlled trial, patients with chronic hepatitis B and hepatic steatosis were randomised 1:1 to high-intensity interval training over 12 weeks or no intervention. The primary outcome was reduction in liver fat-fraction (≥ 2.8%), assessed by magnetic resonance imaging. Secondary outcomes were body composition, indices of glucose metabolism, blood lipids, blood pressure, alanine aminotransferase, physical fitness assessed by maximal oxygen consumption (VO2max), and self-assessed health. The trial was discontinued before reaching the planned sample size due to slow recruitment. Nineteen patients were included, and 14 completed the trial (seven per group). Changes in liver fat-fraction showed a between-group difference of -2.03% [95% CI: -5.5 to 1.4; p = 0.22]. Exercising patients improved VO2max by 5.6 mL/kg/min [1.7 to 9.5; p < 0.05] and emotional well-being by 18.07 points [6.6 to 29.6; p < 0.05]. The exercise intervention did not affect total body fat -0.35% [-2.8 to 2.1] or lean body mass 0.6 kg [-0.7 to 1.9]. Changes in glucose tolerance, insulin secretion, Matsuda index -0.89 [-2.5 to 0.5; p = 0.18], cholesterol 0.29 mmol/L [-0.3 to 0.9; p = 0.32] and systolic blood pressure 6.36 mmHg [-6.4 to 19.1; p = 0.29] did not differ significantly between groups. We did not observe a significant effect of high-intensity interval training on liver fat-fraction in patients with chronic hepatitis B and hepatic steatosis. Due to premature discontinuation and the resulting limited sample size, the study was underpowered, and the findings should be interpreted as exploratory. Nevertheless, the intervention improved physical fitness and emotional well-being.
Clinical relevance
In patients with both chronic hepatitis B and confirmed hepatic steatosis, does a 12-week supervised high-intensity interval training (HIIT) program produce a clinically meaningful reduction (≥2.8%) in liver fat-fraction compared with no intervention? __SNAPSHOT__ {"studyDesign":"Randomized controlled trial (unblinded, 1:1 allocation); trial terminated early due to slow recruitment","setting":"Academic university hospitals, Copenhagen, Denmark (Center for Physical Activity Research, Rigshospitalet; Department of Infectious Diseases, Hvidovre Hospital; and affiliated centers)","sampleSize":"Randomized n=19; completed n=14 (HIIT: n=7, control: n=7); planned sample size n=30 — not reached","population":"Adults with confirmed chronic hepatitis B infection and hepatic steatosis; specific inclusion/exclusion criteria (e.g., age range, HBV treatment status, degree of steatosis threshold) not fully reported in the abstract","intervention":"Supervised HIIT on ergometer bicycles, three sessions per week, 40 minutes per session (10-min warm-up, 25-min 4×4 interval protocol at high intensity, 5-min cool-down), over 12 weeks","comparator":"No intervention (usual care control)","primaryOutcome":"Reduction in liver fat-fraction of ≥2.8%, assessed by MRI (IDEAL-IQ technique)","followUp":"12 weeks (intervention period); post-intervention assessment timepoint only — longer-term follow-up not reported","fundingSource":"Not reported in the abstract; one co-author (Sten Madsbad) declared advisory board memberships and research grant relationships with Novo Nordisk, Boehringer Ingelheim, and others, stated to be unrelated to this work"}
Key findings
The primary outcome — a clinically meaningful reduction in liver fat-fraction (≥2.8%) — was not achieved. The between-group difference in liver fat-fraction was −2.03% (95% CI: −5.5 to +1.4; p=0.22), which did not reach statistical significance and did not cross the pre-specified minimum clinically important difference threshold of 2.8%. Among secondary outcomes, the HIIT group demonstrated a statistically significant improvement in VO2max of +5.6 mL/kg/min (95% CI: 1.7 to 9.5; p<0.05) and a significant improvement in emotional well-being of +18.07 points (95% CI: 6.6 to 29.6; p<0.05). The exercise intervention did not produce significant between-group differences in total body fat (−0.35%; 95% CI: −2.8 to 2.1), lean body mass (+0.6 kg; 95% CI: −0.7 to 1.9), glucose tolerance, insulin secretion, Matsuda index (−0.89; 95% CI: −2.5 to 0.5; p=0.18), total cholesterol (+0.29 mmol/L; 95% CI: −0.3 to 0.9; p=0.32), or systolic blood pressure (+6.36 mmHg; 95% CI: −6.4 to 19.1; p=0.29). Results for ALT and other lipid parameters are not reported in the abstract. NNT is not calculable from the data provided. Serious adverse events are not reported in the abstract.
Practice implications
This trial is the first randomized exercise intervention study conducted specifically in patients with chronic hepatitis B and concomitant hepatic steatosis — a population with heightened risk of cirrhosis and hepatocellular carcinoma due to the compounded hepatic burden of both conditions. The study did NOT establish that 12 weeks of supervised HIIT reduces liver fat-fraction in this population; the primary outcome was non-significant and did not achieve the pre-specified clinically important threshold. The trial was explicitly terminated before reaching its planned sample size of 30 participants (only 14 of 30 completed), rendering it severely underpowered to detect the targeted effect. As such, the null result cannot be interpreted as evidence of true inefficacy — the study was insufficiently powered to rule out a clinically meaningful benefit. The significant improvements in VO2max and emotional well-being are encouraging signals but must be interpreted cautiously given the small sample, multiple secondary outcomes tested, and absence of correction for multiplicity. The findings do not apply to patients with HBV without steatosis, those with advanced fibrosis or cirrhosis, or populations outside Northern European tertiary-care hepatology settings. Only an abstract was available for review; full-text data on safety, adherence, baseline characteristics, HBV treatment status, and fibrosis stage could meaningfully affect interpretation. __LIMITATIONS__ Trial terminated early due to slow recruitment; only 14 of 30 planned participants completed — critically underpowered for the primary outcome (power to detect the pre-specified MCID is not reported but is expected to be substantially below 80%),Very small per-group sample size (n=7 per arm) makes all effect estimates highly unstable and the confidence intervals wide and uninformative,Unblinded design — participants and treating personnel were aware of group allocation, introducing risk of performance and detection bias, particularly for subjective secondary outcomes such as self-assessed health,Short 12-week follow-up does not permit assessment of durability of any effects on liver fat, metabolic parameters, or clinical endpoints such as fibrosis progression,No correction for multiple secondary outcome comparisons is mentioned, raising concern for inflated type I error on statistically significant secondary findings (VO2max, emotional well-being),Generalizability is limited: single-country (Danish), tertiary academic center setting; patient characteristics (HBV treatment status, fibrosis stage, degree of steatosis at baseline, ethnicity) not fully described in the abstract,Selection bias is plausible given the difficulty of recruitment and a 26% dropout rate (5 of 19 did not complete); characteristics of non-completers are not described,No long-term hepatic clinical outcomes (cirrhosis, hepatocellular carcinoma, liver-related mortality) were assessed — surrogate endpoint (MRI liver fat-fraction) only,Funding source and potential conflicts of interest are not fully transparent in the abstract; one co-author has declared relevant industry relationships __BOTTOM_LINE_CATEGORY__ low_certainty __BOTTOM_LINE__ This small, early-terminated RCT (n=14 completers) did not demonstrate a statistically or clinically significant reduction in liver fat-fraction with 12 weeks of supervised HIIT in patients with chronic hepatitis B and hepatic steatosis. The study was critically underpowered and cannot be used to conclude that HIIT is ineffective in this population. A significant improvement in cardiorespiratory fitness (VO2max) provides a rationale for larger, adequately powered trials, but practice should not change on the basis of these data alone.