Rifaximin treatment for metabolic-associated fatty liver disease

Efficacy and Safety of Rifaximin in Treating Metabolic Associated Fatty Liver Disease: A Pilot Trial

This trial tests whether taking oral rifaximin for 24 weeks helps adults with metabolic-associated fatty liver disease (MAFLD) and is safe.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Changzheng Hospital (Academic / other)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07185932 on ClinicalTrials.gov

What this trial studies

This single-center, single-arm early phase 1 study will enroll up to 40 adults with MAFLD who meet specified metabolic criteria. Participants will take oral rifaximin 1200 mg per day (400 mg three times daily) for 24 weeks while maintaining usual activity and following dietary recommendations. Investigators will monitor liver-related labs, metabolic markers, safety labs, and collect mechanistic measures to explore how rifaximin may influence disease progression. Concomitant stable hepatoprotective, lipid-lowering, and antihypertensive therapies are allowed but will be closely monitored.

Who should consider this trial

Good fit: Adults aged 18–75 with a recent diagnosis of MAFLD and at least one metabolic abnormality (for example overweight/obesity, type 2 diabetes, or defined metabolic dysfunction) who can give informed consent are ideal candidates.

Not a fit: Patients with advanced liver disease, non‑metabolic causes of fatty liver, known contraindications to rifaximin, or inability to attend study visits or adhere to the regimen are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If effective, rifaximin could reduce liver fat and inflammation and improve metabolic markers in people with MAFLD.

How similar studies have performed: Rifaximin is established for hepatic encephalopathy and some small human and preclinical studies suggest gut-targeted antibiotics may modestly improve liver inflammation or metabolic measures in NAFLD/MAFLD, but strong evidence in MAFLD is limited.

Eligibility criteria

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

Where this trial is running

Shanghai, Shanghai Municipality

• Changzheng Hospital, Naval Medical University, shanghai, China — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Chuan Yin, M.d.

Conditions Metabolic-associated Fatty Liver Disease; metabolic-associated fatty liver disease; Rifaximin