Severe Dietary Energy Restriction for Compensated Cirrhosis Due to Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomised Controlled Trial

IF 9.4 1区 医学 Q1 GERIATRICS & GERONTOLOGY
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.

Abstract Image

严格的饮食能量限制对代偿性肝硬化由于代谢功能障碍相关脂肪变性肝病:一项随机对照试验
背景:代偿性肝硬化由代谢功能障碍相关的脂肪变性肝病(CC-MASLD)增加发病率和死亡率风险,但没有病因特异性治疗。我们研究了严格能量限制的安全性和有效性信号。在这项随机对照试验中,三级肝病中心的CC-MASLD和肥胖成人患者被随机分为2:1,接受一对一的远程饮食支持,包括低能量(880千卡/天,80克蛋白质/天)的总饮食替代方案,为期12周,然后再进行12周的阶梯食物重新引入或标准护理(SoC)。考虑到该研究的探索性,三个预先定义的共同主要结局被用于评估安全性和有效性信号:肝脏生化严重升高、铁校正T1的变化以及磁共振弹性成像显示肝脏硬度的变化。次要观察结果为磁共振肝脂肪变性的变化、基于体能测试和肝脏脆弱指数的体能变化、无脂块的变化。磁共振结果采用盲法评估。在2022年2月至2023年9月期间,17名参与者(36%为女性,中位[IQR]年龄58[7.5]岁)被随机分为SoC组(n = 6)或干预组(n = 11)。由于招募速度缓慢,试验比计划提前停止。91%和94%的参与者分别完成了干预并参加了24周的随访。与SoC相比,24周时干预组间体重变化为- 11.9 kg (95% CI: - 17.2, - 6.6, p < 0.001)。在整个试验过程中,每个人的肝脏生化指标(谷丙转氨酶、天冬氨酸转氨酶和总胆红素)都是稳定的。铁校正T1和脂肪变性显著降低(分别为- 149.9 ms [95% CI - 258.1, - 41.7, p = 0.01]和- 6% [95% CI - 11.3, - 0.6, p = 0.03])。肝脏硬度(0.2 kPa [95% CI−1.1,1.6])、体能测试(1.5点[95% CI−1.9至4.9],p = 0.70)或肝脏脆弱指数(0 [95% CI−0.6至0.6],p = 0.97)的变化在组间无差异。与SoC相比,绝对无脂质量减少(- 3.2 kg [95% CI - 6至- 0.3],p = 0.04),但相对无脂质量占总体重的百分比增加(5.4% [95% CI - 0.5至10.3],p = 0.046)。没有参与者符合预先定义的加强观察或停止干预的安全标准。在心血管指标的变化方面没有组间差异,也没有肝失代偿或严重不良事件的证据。结论:对于CC-MASLD患者,严格的能量限制似乎是实现显著体重减轻和减少肝脏脂肪而无不良反应的安全选择。需要更大规模的研究来证实这些发现。临床试验注册号ISRCTN13053035,前瞻性注册,整体研究状态:已结束。
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来源期刊
Journal of Cachexia Sarcopenia and Muscle
Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-
CiteScore
13.30
自引率
12.40%
发文量
234
审稿时长
16 weeks
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.
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