Severe Dietary Energy Restriction for Compensated Cirrhosis Due to Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomised Controlled Trial
Dimitrios A. Koutoukidis, Susan A. Jebb, Jeremy W. Tomlinson, Ferenc E. Mozes, Michael Pavlides, Miriam Lacharie, Francesca Saffioti, Paul Aveyard, Jeremy F. Cobbold
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引用次数: 0
Abstract
Background
Compensated cirrhosis due to metabolic dysfunction-associated steatotic liver disease (CC-MASLD) increases morbidity and mortality risk but has no aetiology-specific treatment. We investigated the safety and efficacy signals of severe energy restriction.
Methods
In this randomised controlled trial, adults with CC-MASLD and obesity in a tertiary hepatology centre were randomised 2:1 to receive one-to-one remote dietetic support with a low-energy (880 kcal/day, 80 g protein/day) total diet replacement programme for 12 weeks and stepped food reintroduction for another 12 weeks or standard of care (SoC). Given the exploratory nature of the study, three pre-defined co-primary outcomes were used to assess safety and efficacy signals: severe increases in liver biochemistry, changes in iron-corrected T1, and changes in liver stiffness on magnetic resonance elastography. Changes in liver steatosis on magnetic resonance imaging, physical performance based on the physical performance test and liver frailty index, and changes in fat-free mass were secondary outcomes. Magnetic resonance outcomes were assessed blind.
Results
Between February 2022 and September 2023, 17 participants (36% female, median [IQR] age 58 [7.5] years) were randomised to SoC (n = 6) or intervention (n = 11). The trial stopped earlier than planned due to slow recruitment rate. 91% and 94% of participants completed the intervention and attended the 24-week follow-up, respectively. Compared with the SoC, the between-group weight change in the intervention was −11.9 kg (95% CI: −17.2, −6.6, p < 0.001) at 24 weeks. Liver biochemistry markers (alanine transaminase, aspartate transaminase, and total bilirubin) were stable in everyone throughout the trial. Iron-corrected T1 and steatosis significantly reduced (−149.9 ms [95% CI −258.1, −41.7, p = 0.01] and −6% [95% CI −11.3, −0.6, p = 0.03], respectively). There were no between-group differences in changes in liver stiffness (0.2 kPa [95% CI −1.1, 1.6]), the physical performance test (1.5 points [95% CI −1.9 to 4.9], p = 0.70) or the liver frailty index (0 [95% CI −0.6 to 0.6], p = 0.97). Compared with SoC, absolute fat-free mass reduced (−3.2 kg [95% CI −6 to −0.3], p = 0.04) but relative fat-free mass as percentage of total body weight increased (5.4% [95% CI 0.5 to 10.3], p = 0.046). No participant met the pre-defined safety criteria for enhanced observation or intervention discontinuation. There was no between-group differences in changes in cardiovascular markers and no evidence of hepatic decompensation or serious adverse events.
Conclusions
Severe energy restriction appears a safe option to achieve significant weight loss and reduce liver fat without adverse effects in people with CC-MASLD. A larger study is needed to confirm these findings.
Clinical Trial Registration
ISRCTN13053035, prospectively registered, overall study status: closed.
期刊介绍:
The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.