Liquid Biopsy for NASH and Liver Fibrosis

Study Overview
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Brief Summary
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Nonalcoholic fatty liver disease (NAFLD) has evolved to represent the most common cause of chronic liver disease globally. Today, NAFLD is a leading indication for liver transplantation and a major etiology for hepatocellular carcinoma (HCC) in the United States. NAFLD is characterized by the excess accumulation of lipids within the liver and ranges from isolated steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by the presence of hepatic necroinflammation, hepatocyte ballooning and fibrosis progression. Currently, liver biopsy remains the gold standard for the diagnosis of various chronic liver diseases, and for determining the severity of liver injury, inflammation, and fibrosis stage. However, this procedure is invasive, prone to complications such as bleeding and is associated with sampling variability and limited representation of the whole liver. Other limitations include, the difficulty to monitor liver injury progression over time and underestimation of disease severity. Despite intensive research, currently available non-invasive blood tests are not sufficiently sensitive or specific and are therefore of limited use. Blood biomarkers might provide significant advances in the diagnosis and monitoring of disease progression and regression in clinical settings. Recently, liquid biopsy has emerged as a potential, less invasive, alternative to liver biopsy. In fact, it addresses several unmet clinical needs, including sensitivity, specificity, the determination of prognoses, and the prediction of therapeutic responses.

Detailed Description
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This is a multicentric prospective observational study to validate blood non-invasive biomarkers for NASH and fibrosis stage. 150 subjects will be enrolled; 100 subjects with biopsy-proven NASH and 50 subjects with normal liver will be used as controls.

Official Title
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Liquid Biopsy as a Non-invasive Tool for the Diagnosis of NASH and Liver Fibrosis

Conditions
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NASH - Nonalcoholic Steatohepatitis, Liver Fibroses

Intervention / Treatment
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* Diagnostic Test: Liver Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One hundred subjects with NASH documented by liver biopsy and no evidence of another form of liver disease with a BMI ≥30 and ≤55 kg/m2. Fifty subjects with normal liver who underwent laparoscopic elective cholecystectomy, but otherwise in healthy conditions, will be used as controls. Exclusion Criteria: Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous 6 months; Liver cirrhosis; End stage renal failure; Participation in any other concurrent therapeutic clinical trial; Any other life-threatening, non-cardiac disease; Pregnancy; Inability to give informed consent; Substantial alcohol consumption (>20 g/day for women or >30 g/day for men); Wilson's disease; Lipodystrophy; Parenteral nutrition; Interfering medications (e.g., amiodarone, methotrexate, tamoxifen, corticosteroids).
Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Subjects with NASH documented by liver biopsy<br>One hundred subjects with NASH documented by liver biopsy and no evidence of another form of liver disease with a BMI ≥30 and ≤55 kg/m2. | Diagnostic Test: Liver Biopsy<br>* Fine-needle liver biopsy<br>|
| Healhy Donor<br>Fifty subjects with normal liver who underwent laparoscopic elective cholecystectomy, but otherwise in healthy conditions, will be used as controls. | Diagnostic Test: Liver Biopsy<br>* Fine-needle liver biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary aim of our study is to validate blood non-invasivebiomarker sensitivity and accuracy in predicting NASH and fibrosis stage. |  | 2 months |