Efficacy and Safety of Rifaximin in Treating MAFLD

Proportion of patients achieving ≥30% reduction in liver fat content measured by MRI-PDFF at 24 weeks of treatment compared to baseline

Absolute and relative changes in MRI-measured liver PDFF at 12 weeks 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.

Changes in liver function parameters from baseline after 12 weeks of treatment.

Changes in liver function indicators after 24 weeks of treatment compared to baseline.

Change in controlled attenuation parameter (CAP) values, measured by FibroScan, from baseline after 12 weeks of therapy

Change in controlled attenuation parameter (CAP) values, measured by FibroScan, from baseline after 24 weeks of therapy

FLI is utilized to assess the severity of hepatic steatosis. Its calculation formula is based on laboratory and anthropometric measurements, including triglyceride (TG) and gamma-glutamyl transferase (GGT) levels, body mass index (BMI), and waist circumference (WC).

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

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.

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.

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.

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.

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.

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.

BMI calculation Formula:

BMI = Weight (kilograms) ÷ [Height (meters)]²

Waist circumference (WC) is measured 3 cm above the navel.

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).

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).

Cholesterol testing should be performed in the morning after an overnight fast.

Triglyceride testing should be performed in the morning after an overnight fast.

Change from baseline in HbA1c absolute concentration (mmol/mol) and percentage of total hemoglobin (%) 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.

The safety assessment involved monitoring changes in symptoms, vital signs, and laboratory parameters during treatment.