Nonalcoholic Fatty Liver Disease - Intermittent Calorie Restriction (FLICR) Study

Effect of 12-week Intermittent Calorie Restriction on Liver Fat Content in Comparison With Standard-of-care in Patients With Nonalcoholic Fatty Liver Disease: a Randomized Controlled Trial

Several diets have been proposed to reduce liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD), and various effects on liver steatosis have been observed. The objective of this trial is to compare the effects of intermittent calorie restriction (ICR) (5:2 diet) and standard-of-care (SoC) on reduction of hepatic steatosis.

This is an open-label randomised controlled trial of patients with NAFLD. Patients are recruited in the Liver Outpatient Clinic of the Ewha Womans University Mokdong Hospital. The department of Nutritional Science and Food Management, Ewha Womans University will collaborate for this study.

About 72 patients (36 patients with body mass index [BMI] ≥25 kg/m2 and 36 patients with BMI <25 kg/m2) will be enrolled in a 1:1 ratio to 12 weeks treatment with either 5:2 diet (ICR group, 18 patients in each BMI group), or general lifestyle advice from a hepatologist (standard of care; SoC group, 18 patients in each BMI group).

Beginning in week 3 (Visit 2), an ICR group and a SoC group are generated through randomisation. Both arms will be accompanied for a duration of 12 weeks. After 12 weeks from the completion of the experimental phase (wash-out period), there will be the "end of follow up" visit.

The whole duration of the study is 26 weeks (2 weeks lead-in, 12 weeks intervention and 12 weeks post-intervention investigation).

Magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) and MR-Elastography are conducted at the screening visit and at weeks 12.

There will be 5 visits at the study center (screening, randomization, week 8, end of treatment and end of study) and 10 phone visits (week 4, 5, 6, 7, 8, 10, 11, 12, 13, 14). At each visit clinical events, anthropometric index and standard laboratory parameters will be collected. Participants will fill in questionnaires capturing quality of life.

Adverse events will be recorded. Phone visits are used to survey the safety of patients.

Non-adherence to ICR for 20% of the total study period has been selected as cut off to define treatment failure at per-protocol analysis.

Inclusion Criteria:

1. NAFLD diagnosed by (1) Histologic assessment with a fat accumulation of more than 5% of the liver's weight in a biopsy, or (2) Radiologic assessment with a MRI-PDFF ≥8%.
2. Age between 19 and 75 years
3. Capability to understand the study and the individual consequences of participation
4. Signed and dated declaration of agreement in the forefront of the study

Exclusion Criteria:

1. Daily alcohol consumption >30 g in men and >20 g in women
2. Other causes of chronic liver disease (HBV, HCV, HDV, HEV, HIV), autoimmune diseases or chronic cholestatic liver disease, drug induced liver injury, hereditary haemochromatosis, Wilson disease, α-1-Antitrypsin deficiency
3. Liver cirrhosis
4. Hepatocellular carcinoma
5. Medications which cause liver disease or secondary NAFLD (e.g. Tamoxifen, systemic Corticosteroids, Methotrexate, Tetracycline, Estrogens, Valproic acid)
6. Changes in body weight > 5% in the last 3 months
7. Intake of medical treatment for NAFLD/NASH in the last 6 months (except for vitamin E)
8. Diabetes
9. Pregnancy
10. Patients after organ transplantations
11. Missing or lacking consent capability