Clinical trial NCT04785937: Accuracy of Imaging Techniques in Diagnosing Steatohepatitis and Fibrosis in NAFLD Patients
Official title: Accuracy of Imaging Techniques Including Ultrasound and Magnetic Resonance Imaging in the Diagnosis of Steatohepatitis and Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease: Comparison With the Histological Reference Standard
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non-Alcoholic Fatty Liver Disease
Steatohepatitis, Nonalcoholic
Liver Fibroses
Keywords: Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Diagnostic Ultrasound
Biopsy
Non-Inferiority Trial
Lead sponsor: Azienda USL Reggio Emilia - IRCCS
Sponsor class: OTHER_GOV
First posted: 2021-03-08
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: The estimated overall global prevalence of non-alcoholic fatty liver disease (NAFLD) is around 25% and projected at 33.5% in 2030. While simple steatosis without evidence of inflammation and hepatocellular injury (non-alcoholic fatty liver) is generally a benign condition, non-alcoholic steatohepatitis (NASH) can progress to fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. Since only histological analysis can accurately evaluate NAFLD patterns, liver biopsy is the gold standard for assessment, and it should be considered in patients who are at increased risk of having steatohepatitis and/or fibrosis. Major drawbacks are its invasive nature, risk of complications, sampling errors and inter and intra-observer variability. Currently, there are no approved therapies for NASH. However, several drugs are now in phase 2 and 3 trials, and results are expected in 1-2 years. If medical treatments become available, screening for steatohepatitis and fibrosis will be recommended in high-risk patients. The lack of non-invasive tools to identify patients who may benefit from a therapeutic intervention is a central issue. Should liver biopsy be avoided or reserved for a more limited number of undetermined or high-risk patients, the benefit-harm balance of NASH screening and therapies would undergo a major change. Some imaging methods, mostly ultrasound (US) or Magnetic Resonance (MR) techniques, have shown promising potential in fibrosis and NASH diagnosis.

The objective of this study is to evaluate the diagnostic accuracy of non-invasive imaging techniques including US and MR methods, 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 ultrasound (US), including shear wave elastography (SWE) with liver stiffness measurement and US- fatty liver index (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. 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: Inclusion Criteria:

* clinical indication to perform a liver biospy for NAFLD assessment based on all of the following:

  1. presence of liver steatosi at ultrasound
  2. at least one risk factor for NASH/fibrosis (obesity, or type 2 diabetes mellitus, or metabolic syndrome)
  3. 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

Exclusion Criteria:

* 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)
* contraindications to perform magnetic resonance (pace-maker, claustrophobia, pregnancy, MR-unsafe metallic implants)

Primary outcomes:
measure: False positives
timeFrame: baseline
measure: False negatives
timeFrame: baseline
measure: Sensitivity
timeFrame: baseline
measure: Specificity
timeFrame: baseline
Secondary outcomes:
measure: Correlation of quantitative imaging parameters with histopathological, demographic, anthropometric and clinical characteristics
timeFrame: baseline
measure: Number of patients whit incomplete or unreliable imaging tests
timeFrame: baseline
Other outcomes:
Locations:
city: Reggio Emilia
country: Italy
facility: Azienda USL-IRCCS di Reggio Emilia
state: RE
Study officials:
affiliation: Azienda USL - IRCCS di Reggio Emilia
name: Pierpaolo Pattacini, MD
role: STUDY_DIRECTOR
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