Study Objective: To evaluate the efficacy and safety of Rifaximin-α in the treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), and investigate the underlying mechanisms by which Rifaximin-α influences MASLD progression. Target Population: Patients diagnosed with MASLD. Intervention: This trial is a multicenter, prospective, randomized, controlled study. Enrolled MASLD patients who meet the inclusion criteria, do not meet any exclusion criteria, and provide written informed consent will be randomized in a 2:1 ratio to the Rifaximin-α treatment group (40 cases) or the control group (20 cases). All patients are advised to maintain daily physical activity and follow a recommended dietary plan (e.g., Mediterranean diet). The Rifaximin-α treatment group will receive oral Rifaximin-α at a dose of 1200 mg per day for 24 weeks. Both groups of patients will enter a 24-week follow-up period after completing the 24-week treatment. During the study, patients' existing foundational treatments (such as liver-protecting, lipid-lowering, glucose-lowering, and antihypertensive therapies) will be maintained. Relevant indicators will be closely monitored. And avoid the use of medications known to alter the gut microbiota, such as lactulose, antibiotics, and various types of intestinal microecological preparations. Investigational Drug: Rifaximin-α (Alfa Wassermann S.p.A., Italy).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Participants in the treatment group will receive oral Rifaximin-α at a dosage of 1200 mg/day (400 mg, three times daily) for 24 weeks.
Changzheng Hospital, Naval Medical University, shanghai, China
Shanghai, China
RECRUITINGThe relative change in liver fat content measured by MRI from baseline to 24 weeks.
The relative changes in MRI-measured liver proton density fat fraction (PDFF) at 24 weeks compared to baseline.
Time frame: From enrollment to the end of treatment at 24 weeks
The absolute change in liver fat content measured by MRI from baseline to 24 weeks.
Absolute changes in MRI-measured liver proton density fat fraction (PDFF) at 24 weeks compared to baseline.
Time frame: From enrollment to the end of treatment at 24 weeks
Proportion of patients achieving ≥30% reduction in liver fat content measured by MRI-PDFF at 24 weeks of treatment compared to baseline
Proportion of patients achieving ≥30% reduction in liver fat content measured by MRI-PDFF at 24 weeks of treatment compared to baseline
Time frame: From enrollment to the end of treatment at 24 weeks
The change in liver fat content measured by MRI-PDFF at 12 weeks of treatment
Absolute and relative changes in MRI-measured liver PDFF at 12 weeks compared to baseline.
Time frame: From enrollment to the end of treatment at 12 weeks
Proportion of patients achieving ≥30% reduction in liver fat content (PDFF) measured by MRI at 12 weeks of treatment compared to baseline.
The proportion of patients whose liver fat content (PDFF), assessed via MRI, decreased by ≥30% from baseline after 12 weeks of treatment.
Time frame: From enrollment to the end of treatment at 12 weeks
Changes in serum alanine aminotransferase levels after 12 and 24 weeks of treatment compared to baseline.
Changes in serum ALT levels from baseline after 12 and 24 weeks of treatment
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in serum aspartate aminotransferase levels after 12 and 24 weeks of treatment compared to baseline.
Changes in serum AST levels from baseline after 12 and 24 weeks of treatment
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in serum Gamma-Glutamyl Transferase levels after 12 and 24 weeks of treatment compared to baseline.
Changes in serum GGT levels from baseline after 12 and 24 weeks of treatment
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in serum Alkaline Phosphatase levels after 12 and 24 weeks of treatment compared to baseline
Changes in serum AKP levels from baseline after 12 and 24 weeks of treatment
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Change in liver fat content assessed via FibroScan after 12 and 24 weeks of treatment compared to baseline.
Change in controlled attenuation parameter (CAP) values, measured by FibroScan, from baseline after 12 and 24 weeks of therapy
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in fatty liver index (FLI) after 12 and 24 weeks of treatment compared to baseline.
FLI is utilized to assess the severity of hepatic steatosis and is calculated using the following formula: FLI = (e\^(0.953 \* ln(triglycerides) + 0.139 \* BMI + 0.718 \* ln(ggt) + 0.053 \* waist circumference - 15.745)) / (1 + e\^(0.953 \* ln(triglycerides) + 0.139 \* BMI + 0.718 \* ln(ggt) + 0.053 \* waist circumference - 15.745)) \* 100. Interpretation: A FLI value below 30 can be used to rule out steatosis (sensitivity = 87%; negative likelihood ratio \[LR-\] = 0.2), while a FLI value equal to or above 60 can be used to rule in hepatic steatosis.
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in NAFLD-liver fatty score（NAFLD-LFS）after 12 and 24 weeks of treatment compared to baseline.
NAFLD-LFS Calculation Formula: NAFLD-LFS = -2.89 + 0.45 × Type 2 Diabetes (yes=2, no=0) + 1.18 × Metabolic Syndrome (yes=1, no=0) + 0.15 × Insulin (mU/L) + 0.04 × AST (U/L) - 0.94 × (AST/ALT Ratio). Interpretation of Scores: NAFLD-LFS \< -1.0: Suggests low liver fat content and a low likelihood of significant steatosis. -1.0 ≤ NAFLD-LFS ≤ 0.5: Intermediate range; further evaluation with additional tests (e.g., imaging or biopsy) is recommended. NAFLD-LFS \> 0.5: Indicates high liver fat content and the presence of significant steatosis, requiring clinical intervention.
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in AST-to-Platelet Ratio Index (APRI) after 12 and 24 weeks of treatment compared to baseline.
APRI is calculated using the following formula: APRI = \[ (AST Level (U/L) / AST ULN (Upper Limit of Normal)) / Platelet Count (10⁹/L) \] × 100. Interpretation: APRI \< 0.5: Suggests the absence of significant fibrosis (high negative predictive value). APRI \> 2.0: Highly indicative of cirrhosis (high positive predictive value). Intermediate values (0.5 ≤ APRI ≤ 2.0): Further evaluation with additional tests-such as liver elastography, FIB-4 index, or liver biopsy-is recommended for accurate assessment.
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in Fibrosis 4 (FIB-4) Score after 12 and 24 weeks of treatment
The FIB-4 index is primarily used to stratify the risk of liver fibrosis and is calculated using the following formula: FIB-4= Age (years) × AST (U/L)/ \[Platelet Count (10⁹/L)×√ALT(U/L)\]. The criteria are categorized as follows: Low Risk (FIB-4 \< 1.3) suggests minimal or no fibrosis (F0-F1). Liver biopsy or elastography may be deferred in such cases. Intermediate Risk (1.3 ≤ FIB-4 ≤ 2.67): Further evaluation with additional tests-such as liver elastography, APRI, or liver biopsy-is recommended. Significant fibrosis (F2-F3) may be present, warranting closer monitoring. High Risk (FIB-4 \> 2.67): Highly suggestive of advanced fibrosis or cirrhosis (F3-F4). Confirmatory tests like elastography or liver biopsy should be prioritized. This range has a high positive predictive value.
Time frame: From enrollment to the end of treatment at 12 and 24 weeks.
Changes in NAFLD fibrosis score (NFS) after 12 and 24 weeks of treatment compared to baseline.
NFS calculation formula: NFS= \[-1.675+0.037×Age (years)+0.094×BMI （kg/m2+1.13×IFG/Diabetes (yes = 1, no = 0) +0.99）× (AST/ALT Ratio) +0.013×PLT(×109/L)-0.66×ALB（g/dl）\]. Interpretation Guidelines: NFS \< -1.455: Low probability of significant fibrosis (F2-F4). NFS \> 0.676: High probability of advanced fibrosis (F3-F4). NFS between -1.455 and 0.676: Indeterminate range; further evaluation with additional tests (e.g., elastography or liver biopsy) is recommended.
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in FibroScan-AST (FAST) Score after 12 and 24 weeks of treatment compared to baseline.
The FAST Score is a non-invasive composite index used to assess the likelihood of both significant fibrosis (≥F2) and active steatohepatitis (NASH) in patients withMASLD. It integrates Liver Stiffness Measurement (LSM) obtained via FibroScan® and the serum biomarker AST. FAST Score Calculation Formula: FAST = e\^(-1.65 + 1.07 × ln(LSM) + 2.66 × 10\^(-8) × AST\^3 - 63.3 × AST\^(-1) - 0.009 × PLT) / (1 + e\^(-1.65 + 1.07 × ln(LSM) \+ 2.66 × 10\^(-8) × AST\^3 - 63.3 × AST\^(-1) - 0.009 × PLT)). Interpretation Guidelines: FAST \< 0.35: Low probability of significant fibrosis (≥F2) with active inflammation (NASH). Negative predictive value \>90%. Liver biopsy may be avoided. FAST \> 0.67: High probability of both significant fibrosis (≥F2) and active inflammation (NASH). Positive predictive value \>70%. Further evaluation or intervention is recommended. FAST between 0.35-0.67: Gray zone; comprehensive assessment with additional methods.
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in Body Mass Index (BMI) at 12 and 24 weeks of treatment compared to baseline.
BMI calculation Formula: BMI = Weight (kilograms) ÷ \[Height (meters)\]²
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in Waist circumference (WC) at 12 and 24 weeks of treatment compared to baseline.
Waist circumference (WC) is measured 3 cm above the navel.
Time frame: From enrollment to the end of treatment at 12 and 24 weeks.
Changes in visceral adipose tissue (VAT) at 12 and 24 weeks of treatment compared to baseline. [
VAT was quantified using 3D Slicer software by manually segmenting regions of interest (ROIs) within the intra-abdominal cavity on MRI images at the level of the third lumbar vertebra (L3).
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in abdominal subcutaneous adipose tissue (ASAT) from baseline after 12 and 24 weeks of therapy
ASAT volume was quantified using 3D Slicer software by manually segmenting regions of interest (ROIs) within the subcutaneous fat compartment on MRI images at the level of the third lumbar vertebra (L3).
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
Changes in Cholesterol from baseline after 12 and 24 weeks of therapy.
Cholesterol testing should be performed in the morning after an overnight fast.
Time frame: From enrollment to the end of treatment at 12 and 24 weeks.
Changes in triglyceride from baseline after 12 and 24 weeks of therapy.
Triglyceride testing should be performed in the morning after an overnight fast.
Time frame: From enrollment to the end of treatment at 12 and 24 weeks.
Changes in Hemoglobin A1c (HbA1c) from baseline after 12 and 24 weeks of therapy.
Change from baseline in HbA1c absolute concentration (mmol/mol) and percentage of total hemoglobin (%) after 12 and 24 weeks of therapy.
Time frame: From enrollment to the end of treatment at 12 and 24 weeks.
Changes in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) from baseline after 12 and 24 weeks of therapy.
HOMA-IR Calculation Formula: HOMA-IR = \[Fasting Insulin (μIU/mL) × Fasting Glucose (mmol/L)\] / 22.5. Increase in HOMA-IR suggests worsening insulin resistance. Decrease in HOMA-IR indicates improved insulin sensitivity.
Time frame: From enrollment to the end of treatment at 12 and 24 weeks
The frequency and severity of treatment-related adverse events (AEs) as assessed by CTCAE 5.0.
The safety assessment involved monitoring changes in symptoms, vital signs, and laboratory parameters during treatment.
Time frame: From enrollment to the end of treatment at 24 weeks
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