Compensated cirrhosis due to non-alcoholic fatty liver disease Digestive System
Conditions
Interventions
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 nutritiona
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
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* [*Definition of non-histological diagnosis of cirrhosis: Liver stiffness by transient elastography =15 kPA AND ANY of: - imaging evidence of nodular OR irregular liver AND/OR - presence of porto-systemic collateral vessels AND/OR - splenomegaly (without alternative cause) AND/OR - thrombocytopaenia in absence of primary haematological disease.] 5. Stable dose of medication(s) for type 2 diabetes for at least 3 months prior to screening visit. 6. Willing to allow his or her General Practitioner and consultant to be notified of participation in the trial.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 01/08/2023: 1. Evidence for any of the following alternative or co-existing aetiologies: alcohol [alcohol screening tool (AUDIT-C) score =8, and for patients for whom alcohol may have been a contributing factor to their diagnosis of cirrhosis, they will be excluded if they have any history of sustained harmful alcohol intake defined as =35 units for females and =50 units for males per week], active viral hepatitis (subjects cured for hepatitis C virus infection less than 2 years prior to screening are not eligible), haemochromatosis, primary biliary cholangitis, primary sclerosing cholangitis, Wilson disease, severe alpha-1-antitrypsin deficiency (ZZ phenotype), and autoimmune hepatitis . 2. Alcohol intake of =18 units for females and =26 units for males over the last 7 days, as per the NAFLD diagnostic criteria. 3. Platelet count 25 kPa)]. 4. History or presence of hepatic decompensation (jaundice, ascites, hepatic encephalopathy, or variceal haemorrhage). 5. Model for end-stage liver disease (MELD) score = 13. 6. Child-Pugh score =8. 7. Total bilirubin >25.5 µmol/L (Note: Patients with documented Gilbert’s syndrome but conjugated bilirubin within normal range are eligible). 8. ALT =5x upper limit of normal. 9. AST =5x upper limit of normal. 10. INR >1.3. 11. HbA1c >11.3% (>100mmol/mol). 12. Listed for liver transplantation. 13. History of hepatocellular carcinoma or history of hepatocellular carcinoma treatment. 14. HIV infection. 15. Weight loss of 10% or more since diagnostic biopsy or, if biopsy not present, within the last 6 months. 16. Previous bariatric surgery or ileal resection. 17. History of biliary diversion. 18. Acute cholecystitis or acute biliary obstruction. 19. Contraindication to MRI. 20. Documented arrhythmia, except atrial fibrillation, or prolonged QT syndrome. 21. Taking warfarin. 22. Chronic renal failure of stage 4 or 5. 23. Scheduled for elective surgery under general anaesthesia. 24. Female participant who is pregnant, lactating, or planning pregnancy during the course of the trial. 25. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial. 26. Currently taking part in other interventional clinical trials unless approved by the CI. 27. Insulin use for more than 10 years for type 2 diabetes management AND C-peptide <600pmol/L. 28. Type 1 diabetes. 29. Evidence of proliferative retinopathy. _____ Previous exclusion criteria as of 20/10/2022: 1. Evidence for any of the following alternative or co-existing aetiologies: alcohol [alcohol screening tool (AUDIT-C) score = 8], active viral hepatitis (subjects cured for hepatitis C virus infection less than 2 years prior to screening are not eligible), haemochromatosis, primary biliary cholangitis, primary sclerosing cholangitis, Wilson disease, severe alpha-1-antitrypsin deficiency (ZZ phenotype), and autoimmune hepatitis. 2. Alcohol intake of =18 units for females and =26 units for males over the l
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
England, United Kingdom
Outcome results
None listed