Efficacy and Safety of Rifaximin in Treating MAFLD

Inclusion Criteria: 1. Willing and able to provide written informed consent; 2. Aged 18 to 75 years, regardless of gender; 3. Diagnosed with fatty liver disease within the past 6 months; 4. Presence of at least one of the following metabolic abnormalities: (1) Overweight or obesity (BMI ≥23 kg/m²) (2) Type 2 diabetes (T2DM) (3) Clinical evidence of metabolic dysfunction (defined as meeting at least two of the following criteria): A. Waist circumference ≥90 cm for males or ≥80 cm for females B. Blood pressure ≥130/85 mmHg and/or diagnosed hypertension under treatment C. Fasting plasma triglycerides ≥1.7 mmol/L (150 mg/dL) or diagnosed hypertriglyceridemia under treatment D. Fasting HDL-C \<1.0 mmol/L (40 mg/dL) for males or \<1.3 mmol/L (50 mg/dL) for females, or diagnosed dyslipidemia under treatment E. Prediabetes: fasting glucose 5.6-6.9 mmol/L (100-125 mg/dL) or 2-hour postprandial glucose 7.8-11.0 mmol/L (140-199 mg/dL) or HbA1c 5.7%-6.4% (39-47 mmol/mol) F. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score ≥2.5 G. Plasma high-sensitivity C-reactive protein (hs-CRP) \>2 mg/L 5. Liver fat content ≥8% as measured by MRI proton density fat fraction (MRI-PDFF). Exclusion Criteria 1. Cirrhosis - Confirmed by clinical, laboratory, imaging, and/or liver biopsy. 2. Chronic liver disease of other etiologies (e.g., viral/autoimmune hepatitis, alcoholic liver disease, drug-induced liver injury) 3. Secondary hepatic steatosis (e.g., drug-induced, total parenteral nutrition-related, or hypothyroidism-associated); 4. Recent use of intestinal flora-modifying agents, or unstable regimens of medications (including hepatoprotectants, metformin, thiazolidinediones, fibrates, statins, et al) within 4 weeks prior to enrollment; 5. Agents with potential effects on MAFLD progression administered within 12 weeks prior to enrollment, excluding those maintained at stable doses for ≥24 weeks (e.g., Glucagon-like peptide-1 receptor agonists, Dipeptidyl peptidase IV inhibitors, Obeticholic acid, Sodium-glucose cotransporter 2 inhibitors, Resmetirom or anti-obesity medications) 6. Poorly controlled diabetes (HbA1c \>9%) 7. Jaundice (total bilirubin ≥85 μmol/L), or Renal dysfunction (serum creatinine ≥1.2 × ULN) 8. History of bariatric surgery 9. Active or suspected malignancy 10. Severe systemic conditions - Including: Inflammatory diseases (e.g., connective tissue disorders), Biliary/pancreatic disorders, Chronic/acute infections, Severe cardiovascular, pulmonary, or hematologic diseases, Myocardial infarction or stroke within 6 months, Psychiatric disorders 11. HIV infection 12. Known hypersensitivity to rifaximin 13. MRI contraindications - Including: Metal implants, Claustrophobia, Body size exceeding scanner capacity 14. Pregnancy, lactation, or planned pregnancy 15. Participation in another drug trial within 3 months 16. Other conditions deemed unsuitable by investigators