A Multicenter, Randomized, Crossover Clinical Trial Study of Digital Intelligence Software in Patients With MAFLD

Inclusion criteria

• Adult patients aged 18-65 years with a BMI of 24-35 kg/m².
• Confirmed diagnosis of Metabolic-associated Fatty Liver Disease (MAFLD), defined by a FibroScan® result > 248 dB/m or an MRI-PDFF > 5%.
• Willing and able to provide written informed consent and comply with the study protocol, including the use of a compatible smartphone for digital health components.
• If treated for Type 2 Diabetes Mellitus (T2DM), must be on a stable medication regimen for at least 3 months prior to baseline (Day 0), with the expectation to maintain stability throughout the study barring medical necessity.
• If taking medications with potential NASH-remitting effects (e.g., vitamin E, thiazolidinediones), must be on a stable dose for at least 3 months prior to Day 0.

Exclusion criteria

• Subjects were excluded from participation if they met any of the following criteria, based on the most recent pre-randomization assessments:
• Evidence of cirrhosis, defined as histological stage F4 or its clinical equivalent.
• History of heavy alcohol consumption (>30 g/day for males, >20 g/day for females) for more than 3 consecutive months within one year prior to screening.
• Prior or planned solid organ transplantation (excluding corneal transplants).
• Planned bariatric surgery. A history of bariatric surgery was permitted only if weight had been stable (variation <10%) for at least 3 months prior to screening.
• Presence of other chronic liver diseases, including:
• Hepatitis B surface antigen (HBsAg) positivity.
• Hepatitis C virus (HCV) RNA positivity.
• Primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, or overlap syndromes.
• Wilson's disease, alpha-1 antitrypsin deficiency (ZZ phenotype), or hereditary hemochromatosis.
• History of Type 1 Diabetes Mellitus. Uncontrolled Type 2 Diabetes Mellitus, defined as HbA1c >9% or current insulin therapy.
• History of hepatic decompensation events (e.g., ascites, hepatic encephalopathy, variceal hemorrhage).
• Any of the following laboratory abnormalities at screening:
• Platelet count < 150,000/mm³
• Albumin < 3.0 g/dL
• International Normalized Ratio (INR) > 1.3
• Alkaline Phosphatase (ALP) > 2 × Upper Limit of Normal (ULN)
• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 5 × ULN
• Total Bilirubin > 1.3 × ULN (except in cases of documented Gilbert's syndrome)
• Estimated Glomerular Filtration Rate (eGFR) < 60 mL/min/1.73 m²
• Hemoglobin < 10 g/dL
• Uncontrolled thyroid dysfunction, defined as a thyroid-stimulating hormone (TSH) level < 0.1 or > 10 µIU/mL at screening.
• Documented HIV-1 or HIV-2 infection.
• Known Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency.
• Significant cardiovascular history, including myocardial infarction, unstable angina, heart failure, uncontrolled arrhythmia, coronary artery bypass graft, or percutaneous coronary intervention within one year prior to screening.
• Diagnosis of malignancy within the past 2 years (except for adequately treated basal cell carcinoma or cutaneous squamous cell carcinoma).
• Severe co-morbid respiratory, cardiac, cerebrovascular, hepatic, or renal conditions that, in the investigator's judgment, would preclude safe participation in a diet and exercise intervention.
• Active, severe infection requiring parenteral antimicrobial therapy within 30 days of screening.
• Major surgery within 30 days prior to screening.
• Chronic use of medications known to promote hepatic steatosis (e.g., systemic corticosteroids, amiodarone, methotrexate, tamoxifen, valproic acid) within 3 months of screening. Short-term, low-dose corticosteroid use was permissible.
• Current or planned treatment with radiation therapy, cytotoxic chemotherapy, or immunomodulatory agents (e.g., interleukins, interferons).
• Treatment with any investigational agent within 6 months prior to screening, or prior participation in a clinical trial for NASH/MAFLD within 6 months.

Pregnancy or lactation.

1.Any other condition or circumstance that, in the opinion of the Investigator, would compromise patient safety or the validity of the study data.