LiFT 2: Low-energy treatment in compensated cirrhosis
Research type
Research Study
Full title
Safety signals and potential efficacy of a low-energy total diet replacement programme with behavioural support to delay disease progression in compensated cirrhosis due to non-alcoholic fatty liver disease: a feasibility randomised controlled trial
IRAS ID
307043
Contact name
Dimitrios Koutoukidis
Contact email
Sponsor organisation
University of Oxford / Research Governance, Ethics and Assurance team
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Research Summary:
The build-up of fat in the liver can cause inflammation and scarring. This condition is called compensated cirrhosis due to non-alcoholic fatty liver disease (CC-NAFLD). It may require liver transplant and increases the risk of early death. It affects about 200,000 UK adults, most of whom also have obesity.No drug exists to treat CC-NAFLD. Weight loss programmes might improve CC-NAFLD, but only if they lead to large weight loss. One programme that could achieve this is a low-energy diet with professional support. People eat only soups and shakes for 16 weeks (~860 calories/day). Then, slowly over the next 8 weeks, they start eating regular food. The support helps people stick to the programme and develop healthier eating habits. We know people lose weight rapidly and lower their heart disease risk. This may also treat CC-NAFLD, but a concern exists that rapid weight loss may worsen liver scarring. Here we will test the programme in a few people with detailed monitoring of the health of their liver to see if this concern is a reality.
We will recruit 24 adults with CC-NAFLD and excess weight. A computer will decide at random if patients continue with their care as usual (n=8) or are offered the programme (n=16). We will see whether enough patients will take part, stick to the programme, and return for follow-ups. We will examine whether the treatment appears to be safe at 2, 4, 16, and 24 weeks with blood tests. If there are signs of worsening, we will stop the treatment. At the start of the programme and at 24 weeks, we will also do a detailed liver scan. We will monitor changes in weight and physical function.
With this information, we will plan a large trial to test whether this programme can delay progression of CC-NAFLD.
Summary of Results:
People with compensated cirrhosis caused by metabolic dysfunction–associated steatotic liver disease (MASLD) have increased health risks, but there is no treatment that targets the underlying cause. We tested whether a very low-calorie, high-protein total diet replacement could be safe and show signals of benefit.In this randomised trial, adults with compensated MASLD-related cirrhosis and obesity were assigned 2:1 to either remote one-to-one dietitian support with 880 kcal/day (80 g protein/day) for 12 weeks plus stepped food reintroduction for 12 weeks, or standard care. Seventeen participants were enrolled; the study stopped early due to slow recruitment, but most completed follow-up.
Compared with standard care, the intervention led to much greater weight loss (about 12 kg more by 24 weeks). Liver blood tests remained stable in everyone, and no participants met safety criteria for extra monitoring or stopping the programme. We also saw reductions in liver fat and improvement in an MRI marker (iron-corrected T1), but no clear differences in liver stiffness or physical performance/frailty. Absolute lean mass decreased, though lean mass as a percentage of body weight increased. There were no serious adverse events or signs of liver decompensation.
Overall, severe energy restriction with dietitian support appears safe in this small study and may reduce liver fat in people with compensated MASLD-related cirrhosis; a larger study is needed to confirm these findings.
REC name
South Central - Oxford B Research Ethics Committee
REC reference
21/SC/0408
Date of REC Opinion
23 Dec 2021
REC opinion
Further Information Favourable Opinion