About this trial
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition, and when fatty liver is associated with inflammation and hepatocellular injury (steatohepatitis), it can lead to fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. Liver biopsy is the gold standard for NAFLD assessment but has several drawbacks. Several drugs for NASH are now in phase 2-3 trials, and if medical treatments become available, non-invasive tools to identify patients who may benefit from a therapeutic intervention will be strongly needed. Some imaging methods have shown promising potential in fibrosis and NASH diagnosis. This study aims to evaluate the diagnostic accuracy of non-invasive imaging methods, including ultrasound (US) and Magnetic Resonance (MR) techniques, in diagnosing NASH and fibrosis in patients with or at high risk of NAFLD, using liver biopsy as the reference standard. Consecutive patients with a clinical indication for liver biopsy assessment of NAFLD are enrolled in this non-inferiority study. They undergo both a liver US and a multiparametric unenhanced liver MR examination. As reference standard, histological diagnosis of fibrosis and steatohepatitis made according to the fatty liver inhibition of progression (FLIP) algorithm is used. Sensitivity and specificity of imaging parameters alone or in different combinations will be calculated with the aim of finding one or more tests with at least 90% sensitivity/specificity compared to liver biopsy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
presence of liver steatosi at ultrasound
at least one risk factor for NASH/fibrosis (obesity, or type 2 diabetes mellitus, or metabolic syndrome)
increased liver enzymes (at least one of: GOT>40 U/l, GPT>49 U/l, GGT>75 U/l) or high NAFLD fibrosis score (>0.675), or intermediate NAFLD fibrosis score (between -1.455 and 0.675) and increased liver stiffness at transient elastography (>7 KPa).
consent to participate in the study
Disqualifiers
age < 18 years
secondary causes of liver steatosis (moderate to severe alcohol consumption, steatogenic drugs)
known diffuse liver diseases other than NAFLD (cirrhosis, viral or autoimmune hepatitis, hemochromatosis, amiloidosis, other) or previous primary or secondary liver neoplasms
contraindications to perform liver biopsy (ascites, platelet count<50.000/mmc, INR>1.5, PT>50%, serum bilirubin >3 mg/dL)
Trial design
Single group
Treatments tested in this trial
Ultrasound and Magnetic Resonance
Diagnostic testliver ultrasound (US), including shear wave elastography (SWE) with liver stiffness measurement and US- fatty liver indicator (US-FLI), and a multiparametric unenhanced liver magnetic resonance examination including MR spectroscopy (MRS), Proton Density Fat Fraction (PDFF) and T2\* measurement with Multiecho technique, T1 mapping with Inversion Recovery method, and Intravoxel Incoherent Motion diffusion weighted imaging (IVIM-DWI), measuring different parameters.
Treatment groups
Trial outcomes
Primary outcomes
False positives
false positives of each imaging parameter compared to liver biopsy in the diagnosis of NASH/fibrosis
False negatives
false negatives of each imaging parameter compared to liver biopsy in the diagnosis of NASH/fibrosis
Sensitivity
Sensitivity of each imaging parameter compared to liver biopsy in the diagnosis of NASH/fibrosis
Specificity
Specificity of each imaging parameter compared to liver biopsy in the diagnosis of NASH/fibrosis
Secondary outcomes
Correlation of quantitative imaging parameters with histopathological, demographic, anthropometric and clinical characteristics
Correlation of imaging parameters (US-FLI, US-SWE, MR-PDFF, MR-T1, MR-T2\*, MR-IVIM coefficients, MRS metabolites) with histopathological (percentage of steatosis, lobular inflammation, hepatocellular ballooning, fibrosis), demographic (age, sex), anthropometric (BMI, waist circumference) and clinical (liver enzymes, NAFLD fibrosis score, FIB4) characteristics
Number of patients whit incomplete or unreliable imaging tests
Sponsors and contacts
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