Identification of Liver Fibrosis Biomarkers

Not yet recruiting

• Conditions: Non-alcoholic Steatohepatitis; Non-Alcoholic Fatty Liver Disease; Non-alcoholic Fatty Liver

• Registration Number: NCT06819917
• Lead Sponsor: Roche Diagnostics GmbH

Brief Summary

Chronic liver disease (CLD) is a major cause of global mortality and morbidity . CLD patients are at an increased risk of developing liver fibrosis (formation of scar tissue), cirrhosis and liver failure and are at significant risk to develop primary liver cancer. Non-alcoholic fatty liver disease (NAFLD) represents a major risk for CLD and it is becoming the most common chronic liver condition with an estimated 25% global prevalence. Progression to non-alcoholic steatohepatitis (NASH) occurs in approx. 1 of 5 NAFLD patients and due to the rapidly rising etiology of end-stage liver disease, is currently the second most common etiology of hepatocellular carcinoma (HCC) requiring liver transplantation. Liver biopsy, currently the gold-standard for grading disease activity and staging fibrosis, is invasive, costly and at risk for sampling error. Due to the number of patients diagnosed with fibrosis and since fibrosis stage is prognostic of mortality and drives patient management, it is important to develop noninvasive yet accurate diagnostic tools that can identify fibrosis stage. The purpose of this study is to obtain a panel of clinically well characterized blood specimens to identify novel biomarkers to be used as an aid in diagnosis to assess the stage of clinically significant hepatic fibrosis in patients with signs or symptoms of NAFLD (NAFL/NASH). In addition, quantitative ultrasound (QUS) based approaches combined with artificial intelligence (AI) algorithms will be explored for assessing the stage of fibrosis.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-22
• Status Verified: 2025-02
• Study Start: 2025-02
• Study First Submitted QC: 2025-02-05
• Last Update Submitted: 2025-02-05
• Study First Posted: 2025-02-11
• Last Update Posted: 2025-02-11
• Primary Completion: 2026-09
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 575

Inclusion Criteria

• Patients scheduled for biopsy (or F0-F2 patients that underwent biopsy within the last 6 months but at least 1 month ago) suspected of having hepatic fibrosis due to NAFLD (NAFL/NASH) or patients with MASLD or MASH
• Any FIB-4 value available
• Any Fibroscan value available
• Written and signed informed consent present
• Patients aged ≥ 18 years to ≤ 75 years at the time of the blood draw
• Body Mass Index (BMI) ≤ 45 kg/m²

Exclusion Criteria

• Vulnerable person: person deprived of liberty by a judicial or administrative decision and/or person under psychiatric care
• Self-reported pregnancy or lactating females
• Disease related to other etiologies, including alcoholic liver disease (alcoholic steatohepatitis), MetALD, specific etiology SLD (e.g. DILI or monogenic disease), cryptogenic SLD, viral hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, human immunodeficiency virus, Wilson's disease, Hemochromatosis, alpha-1 antitrypsin deficiency
• Any type of carcinoma, unless it is at least 5 years in remission
• Prior liver transplant
• Evidence of any other unstable or, untreated clinically significant immunological, neoplastic, endocrine, haematological, gastrointestinal, neurological or psychiatric disorder. Medically controlled comorbidities can be allowed
• Self-reported alcohol consumption greater 30 g/day (males) 20 g/day (females)
• Recent myocardial infarction (within last 6 months)
• Inability to have a liver biopsy, or provide blood sample in a fasted status
• F0-F2 recalled patients with +/- 5% change in weight between the biopsy and study inclusion

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Identification of Advanced Fibrosis (≥F3)	Through study completion, an average of 1 year.	he study aims to identify advanced liver fibrosis (stage F3 or higher) through various biomarkers. The assessment will determine the predictive value of these biomarkers for advanced stages of fibrosis (F3-F4)
Identification of Significant Fibrosis (≥F2)	Through study completion, an average of 1 year.	The study aims to identify significant liver fibrosis (stage F2 or higher) through various biomarkers. This involves the comparison of biomarkers to biopsy results to determine their predictive value .

Secondary Outcome Measures

Name	Time	Method
Performance of Biomarkers in Clinically Relevant Subpopulations	Through study completion, an average of 1 year.	Exploratory analysis to evaluate the performance of identified biomarkers within specific patient sub-groups. This aims to understand the variability and reliability of biomarkers across different demographics and clinical characteristics.
Evaluation of Biomarker Panels	Through study completion, an average of 1 year.	This measure involves evaluating individual or combined biomarkers identified through literature review, pathway analysis, and experimental programs using a panel of well-characterized blood specimens (serum, plasma, whole blood, and buffy coat).