Metabolic Dysfunction-associated Steatotic Liver Disease
Conditions
Keywords
MASH
Brief summary
The aim of this multi-center, retrospective epidemiologic study is to confirm the prognostic performance of the Digital Pathology (DP) FibroNest Phenotypic Fibrosis Composite Score (Ph-FCS), derived from standard digital pathology liver biopsy images, in predicting clinical hepatic decompensation events in patients with metabolic dysfunction-associated steatohepatitis (MASH).
Detailed description
MASH (Metabolic Dysfunction-Associated Steatohepatitis): MASH presents histological liver changes similar to those caused by alcohol abuse, but occurs in the absence of alcohol intake. It is common among adults with conditions such as obesity and type-2 diabetes. Severe MASH is expected to become a leading cause of end-stage liver disease. Current Challenges: There are currently no fully approved treatments for MASH which places a significant burden on liver health and transplantation. Diagnosis and assessment rely on subjective histological reviews, which are prone to variability and limitations in detecting subtle changes. Therefore, there is an urgent need for accurate and continuous histological biomarkers. FibroNest Ph-FCS Solution: The FibroNest Ph-FCS offers a promising solution by utilizing high-resolution digital pathology and sophisticated algorithmic methods for sensitive and reproducible fibrosis severity assessment and prediction of clinical events. In a 2003 proof-of-concept retrospective study on 400 patients, the Ph-FCS demonstrated excellent prognostic performance. Proposed Study: This multi-center retrospective study aims to confirm the Ph-FCS's prognostic value using patient liver biopsies and clinical outcome data from the NAFLD Adult Database 2 registry (NCT01030484). The prognostic performance of the Ph-FCS will be compared to: 1. The NASH-CRN Histological Fibrosis Stages established from the same biopsies. 2. Non-invasive biomarkers like Fib-4 and elastography/Fibroscan, also collected retrospectively from the point of initial diagnosis. Study Objectives: (i) Confirm the Ph-FCS's prognostic utility on a large scale. (ii) Compare the Ph-FCS's prognostic performance with that of the NASH-CRN Fibrosis Stages established from the same biopsies. (iii) Compare biopsy-based Ph-FCS with non-invasive biomarkers.
Interventions
Biomarker name: FibroNest Phenotypic Fibrosis Composite Score Acronym: FibroNest Ph- FCS Type of Biomarker: Histologic based, Digital, Quantitative Image Analysis, Imaging modality Definition: A quantitative, normalized (no unit) and continuous composite
Sponsors
PharmaNest, Inc
Nonalcoholic Steatohepatitis Clinical Research Network (NASH)
Virginia Commonwealth University
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Inclusion criteria
From NCT01030484: * Age at least 18 years during the consent process * Willingness to be in the study for 1 or more years * Ability and willingness to give written, informed consent to be screened for and, if eligible, to be enrolled into the Database 2 study * Minimal or no alcohol use history consistent with NAFLD (see
Exclusion criteria
) * Collection of a liver biopsy that is obtained within 120 days of enrollment as part of standard of care or for evaluation in FLINT trial * Collection of biosamples (serum, plasma, DNA, and, if available, liver tissue) within 90 days prior to enrollment and 0-90 days before or 4-90 days after the standard of care liver biopsy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Performance of Hepatic Decompensation Event predictive value of the FibroNest Ph-FCS | Time-to-event analysis between 2 and 10 years | Area under Receiver Operating Characteristic Curve (AUROC) of the FibroNest Ph-FCS, as a prognostic/diagnostic biomarker for liver related events in patients with MASH. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Performance of Hepatic Decompensation Event predictive value of the NASH-CRN Fibrosis Stage | Time-to-event analysis between 2 and 10 years | Area under Receiver Operating Characteristic Curve (AUROC) of the NASH-CRN Fibrosis Stage, as a prognostic/diagnostic biomarker for liver related events in patients with MASH. |
| Performance of Hepatic Decompensation Event predictive value of available non-invasive biomarkers (NITs) including Fib-4 and Elastography by measured by Fibroscan | Time-to-event analysis between 2 and 10 years | Area under Receiver Operating Characteristic Curve (AUROC) of the NIT biomarkers, as a prognostic/diagnostic biomarker for liver related events in patients with MASH. |
| Performance of Hepatic Decompensation Event predictive value of the Collagen Area Ratio (CAR%) as measured by FibroNest | Time-to-event analysis between 2 and 10 years | Area under Receiver Operating Characteristic Curve (AUROC) of the FibroNest CAR%, as a prognostic/diagnostic biomarker for liver related events in patients with MASH. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORArun J Sanyal, MD
Virginia Commonwealth University
STUDY_DIRECTORCynthia Belhling, MD
University California San Diego
STUDY_DIRECTORDavid E Kleiner, MD. PhD
Nonalcoholic Steatohepatitis Clinical Research Network
Outcome results
None listed