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

Plain Language Summary

A severe form of liver disease known as compensated cirrhosis due to metabolic dysfunction-associated steatotic liver disease (CC-MASLD) currently has no drug treatment, with recommendations to lose weight being the primary management strategy. However, the advice to lose weight alone usually only achieves small weight losses in those with CC-MASLD and therefore probably limited effect on liver outcomes. This randomised control trial of 17 individuals with CC-MASLD aimed to examine the effects of a strict low-energy diet. Participants were divided into two groups: one received a very low-calorie diet (880 calories per day) with protein support and diet guidance for 12 weeks, followed by a gradual reintroduction of food over another 12 weeks, while the other group received standard care.

The results showed that this approach resulted in extreme weight loss, primarily body fat and it did result in reductions in liver fat.

This study could be used by healthcare professionals to understand the potential impact of severe dietary energy restriction on patients with compensated cirrhosis due to metabolic dysfunction-associated steatotic liver disease. However, this study was exploratory and in very small numbers so any conclusions should be made with caution.

Expert Review

Reviewer: Karin Elgar

25th Sep 2025

Conflict of interest

None

Take home message

Weight loss induced through low-energy meal replacement programmes may benefit patients with obesity and CC-MASLD in terms of liver fat reduction.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

The aim of this study was to evaluate the signals of safety and efficacy of dietary energy restriction through meal replacements in patients with compensated cirrhosis due to metabolic dysfunction-associated steatotic liver disease (CC-MASLD).

Methods

Single-blind randomised controlled trial.
17 patients with CC-MASLD and a body mass index of ≥30 kg/m² were enrolled.
The intervention consisted of four meal replacements per day (880 kcal and 80g protein) for 16 weeks and gradual reintroduction of healthy food-based meals during weeks 17-22. For the 24 trial weeks participants were supported by a registered dietician.
The control group received brief advice from their hepatologist on healthy eating.
Primary outcomes assessed changes in liver enzymes, changes in iron-corrected T1 (cT1, a marker of fibro-inflammation) and changes in liver stiffness (magnetic resonance elastography).
Secondary outcome measures included markers of severity of liver disease, physical performance, cardiometabolic and anthropometric parameters.

Results

10 of 11 patients in the intervention and 5 of 6 patients in the control group completed the trial.
There were no severe changes in liver enzymes in either group.
At 24 weeks, the intervention group had significant improvements in cT1 (p=0.01), markers of liver fat (p=0.03) and controlled attenuation parameter (p=0.009, measure of hepatic steatosis) compared to the control group.
There were no significant differences in liver stiffness, physical performance, liver frailty index or cardiometabolic markers between groups.
The intervention group lost 11.9 kg more weight than the control group (CI −17.2 to −6.6). Whilst the absolute loss in fat mass was greater in the intervention group, the relative loss was lower (−3.2 (CI −6 to −0.3) and 5.4 (0.5 to 10.3), respectively).

Conclusion

A low-energy meal replacement programme could be a safe and effective strategy to achieve significant weight loss and a reduction of liver fat in patients with obesity and CC-MASLD.

Clinical practice applications

Low-energy meal replacement programme induced weight loss may benefit patients with obesity and CC-MASLD in terms of liver fat reduction.
52 people were invited to participate in this study. Of those, 35 (67%) declined with the primary reason being unwillingness to commit to the intervention - meal replacement programmes are not an easy or popular intervention.

Considerations for future research

Larger and longer-term clinical trials of weight loss through low-energy meal replacement programmes for patients with obesity and CC-MASLD are required to confirm the safety and efficacy of this approach.
Impact on muscle mass should be assessed in future research

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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.