Low-energy total diet replacement in the treatment of compensated cirrhosis

INTERVENTION: The intervention is a low‐energy total diet replacement programme with behavioural support (TDR) and has three phases. In phase 1 (sole source TDR, weeks 0‐16), participants will consume a nutritionally complete package of 4 formula products per day [soups, shakes, and bars (860 kcal/day)]. In phase 2 (food‐re‐introduction, weeks 17‐22), products will be gradually reduced and replaced with food‐based meals. During this phase, participants will consume 3 products per day for weeks 17‐18, 2 products per day for weeks 19‐20, and 1 product per day for weeks 21‐22 together with food‐based meals. In phase 3 (weight maintenance, weeks 23‐24), participants will consume food‐based meals. Participants will have contact with the dietitian for around 15 minutes each week (or 30 minutes fortnightly) over the 24 weeks for behavioural support. This will be over the phone or the app depending on participant preference. Care as usual group: Participants in the comparator control group will receive care as usual which includes, but not limited to, advice for healthy eating and weight loss by their doctor. This will allow for a comparison of the study intervention to the existing standard of care. Randomisation: Participants will be individually randomised with a 2:1 allocation to receive either the intervention or care as usual through minimisation with a 20% random element. The two stratified variables will be BMI (=/< 35 kg/m2) and type 2 diabetes (yes/no). CONDITION: Compensated cirrhosis due to non‐alcoholic fatty liver disease ; Digestive System PRIMARY OUTCOME: ; 1. Biochemistry (ALT, AST, total bilirubin) by blood test ‐ at 0, 2, 4, 16, & 24 weeks; 2. Iron‐corrected T1 relaxation time (cT1) values by magnetic resonance imaging (MRI) ‐ at 0 & 24 weeks; 3. Liver stiffness by magnetic resonance elastography (MRE) ‐ at 0 & 24 weeks; SECONDARY OUTCOME: ; 1. Liver stiffness by transient elastography ‐ at 0, 16, & 24 weeks; 2. Proton density fat fraction (PDFF) on MRI ‐ at 0 & 24 weeks; 3. Controlled attenuation parameter by transient elastography ‐ at 0, 16, & 24 weeks; 4. Enhanced liver fibrosis (ELF) score ‐ at 0 & 24 weeks; 5. UK Model for end‐stage liver disease (UKELD) score ‐ at 0, 4, 16, & 24 weeks; 6. Mortality predicted by Child‐Pugh score ‐ at 0, 4, 16, & 24 weeks; 7. Physical performance test ‐ at 0 & 24 weeks; 8. Adverse events (patien records) ‐ at 0, 2, 4, 16, & 24 weeks; 9. Body weight (kg) ‐ at 0, 4, 16, & 24 weeks; 10. Total fat‐free mass on bioelectrical impedance ‐ at 0, 4, 16, & 24 weeks; 11. Visceral fat on MRI ‐ at 0 & 24 weeks; 12. Muscle mass on MRI ‐ at 0 & 24 weeks; 13. Adjustment in the number and dose of medication ‐ at 0, 4, 16, & 24 weeks; 14. Blood pressure (mmHg, sphygmomanometer) ‐ at 0, 4, 16, & 24 weeks; 15. HbA1c (blood test) ‐ at 0, 16, & 24 weeks; 16. Lipid profile (blood test) ‐ at 0 & 24 weeks; ; Process outcome measures (measured using patient records and case report forms unless noted):; 1. Number of potentially eligible participants ‐ pre‐baseline; 2. Proportion of eligible participants randomised ‐ pre‐baseline; 3. Reasons for non‐enrolment ‐ pre‐baseline; 4. Proportion of intervention sessions attended ‐ at 0, 4, 16, & 24 weeks; 5. Reasons for non‐engagement‐ at 0, 4, 16, & 24 weeks; 6. Proportion of randomised participants completing a 24‐week follow‐up visit ‐ at 24 weeks; 7. Reasons for dropout ‐ at 2, 4, 16, & 24 weeks; 8. Feedback questionnaire ‐ at 24 weeks; 9. Alcohol intake questions ‐ at 0, 4, 16, & 24 weeks; INCLUSION CRITERIA: 1. Participant is able to communicate in English and is willing and able to give informed consent for participation in the trial. 2. Aged =18 years. 3. BMI =30 kg/m² (or BMI =27.5 kg/m² for people of Black, Asian, or minority ethnic origin as per the NICE guidance for obesity screening) 4. Diagnosed with compensated cirrhosis due to non‐alcoholic fatty liver disease based on one of the following: 4a. Biopsy with histological evidence of fibrosis score of 4 [with or without NASH (NASH defined as score of =1 for each of steatosis, inflammation, and ballooning] based on the NASH Clinical Research Network criteria 4b. Previous biopsy with evidence of NASH but with current non‐histological diagnosis of cirrhosis* 4c. Previous biopsy or imaging with evidence of hepatic steatosis but with current nonhistological diagnosis of cirrhosis*