MASLD, SLD, and MASH

Biomarkers in steatotic liver disease (MASLD, SLD)

There is a pressing requirement for new, non-invasive tools to assess the severity of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), worldwide. These tools would aid in monitoring patient progression and stratifying risk for this increasingly prevalent condition.

Nordic Bioscience has developed biomarkers that specifically focus on the progression of liver fibrosis. These biomarkers offer a unique approach to determining the trajectory of patients with MASLD. They can be used to stratify patients based on their risk levels, assess the effectiveness of pharmacological treatments, and enhance the selection of participants for clinical trials, ultimately improving the chances of successful outcomes.

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Nordic ProteinFingerPrint Technology™ biomarkers in MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a condition related to the metabolic syndrome that affects the liver. One of the key factors in determining the prognosis of MASLD is the extent of liver fibrosis, which involves the accumulation of components like collagens in the liver tissue. Nordic Bioscience’s biomarkers specifically target certain neo-epitopes of collagen fragments involved in formation and degradation, which can be detected directly in blood samples.

By using biomarkers that target different types of collagens in the liver, it is possible to determine the origin of the fibrotic tissue being formed and understand the dynamics driving disease progression, such as pericellular fibrosis (involving basement membrane collagens) or bridging fibrosis (involving fibrillar collagens).

Browse our liver biomarker portfolio

NordicPRO-C3™ is a stellar example of a liver-related biomarker

NordicPRO-C3™ is our most widely applied biomarker and has received a letter of support from the FDA for its application in liver disease. NordicPRO-C3™ is very well suited for evaluating ongoing fibrogenesis in patients with advanced fibrosis, stages F3-F4[1]. However, we recommend also assessing fibrolysis (C3M, C4M, C6M), pericellular fibrosis (PRO-C4, PRO-C8), and fibrosis resolution (CTX-III) to evaluate potential treatment effect on all aspects of fibrosis activity in the liver (Figure 1).

 

Figure 1. NordicPRO-C3™ increases with increasing fibrosis and MASLD activity score (NAS).

ADAPT: NordicPRO-C3™-based algorithm for accurate identification of advanced fibrosis in MASLD

NordicPRO-C3™, a diagnostic tool, possesses the capability to accurately identify individuals with both MASH (Metabolic Associated Steatohepatitis) and liver fibrosis who qualify for participation in clinical trials[2,3].

Its effectiveness is further enhanced when integrated into the ADAPT algorithm[4], a comprehensive scoring system that factors in age, platelet count, and the presence of diabetes. Remarkably, ADAPT demonstrates superior predictive accuracy compared to other existing scoring systems when it comes to forecasting advanced fibrosis and MASH, as indicated by the research by Erhardtsen (2021).

Notably, ADAPT surpasses alternative fibrosis scoring methods such as the aspartate aminotransferase to platelet ratio index (APRI), FIB-4, and the NAFLD fibrosis score (NFS) in the identification of significant fibrosis (F2-F4) in individuals afflicted with MASLD (Metabolic Associated Steatohepatitis Liver Disease)[4].

Figure 2. ADAPT is superior to existing fibrosis scores

NordicPRO-C3™ as a secondary endpoint for antifibrotic efficacy

In a phase II study conducted by Madrigal Pharmaceuticals, it was observed that patients who were administered Resmetirom experienced notable reductions in PRO-C3 (nordicPRO-C3™) and MRI-PDFF levels[5].

This study involved patients who were initially divided into two groups: one receiving a placebo (Pbo) and the other receiving Resmetirom (Res) for a duration of 36 weeks. Subsequently, all participants continued with Resmetirom in the open-label extension (OLE) trial for an additional 36 weeks (Figure 3).

 

Figure 3. NordicPRO-C3™ is used as a determinant of treatment efficacy in multiple clinical trials as a secondary endpoint for antifibrotic efficacy
Figure 4. NordicPRO-C3™ as a baseline marker of disease activity and endotyping

NordicPRO-C3™ as a baseline marker of disease activity and endotyping

Harrison et al. demonstrated at EASL 2018 that patients with PRO-C3 (nordicPRO-C3™) greater than or equal to 17.5 ng/mL had a significant reduction in their PRO-C3 (nordicPRO-C3™) level due to Resmetirom (a selective thyroid hormone receptor-β agonist) treatment.

Similar predictive results for Resmetirom were presented by Madrigal Pharmaceuticals at Global NASH Congress 2020 in the extension study when using a baseline level of ≥14 ng/mL nordicPRO-C3™.

Consequently, nordicPRO-C3™ levels >14 ng/mL have been listed as inclusion criteria for the phase III MASH (metabolic dysfunction-associated steatohepatitis) clinical trial MAESTRO-NASH (NCT03900429).

Find biomarkers for liver indications

About MASLD (formerly NAFLD)

  • Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a chronic condition that affects approximately 38% of the global population. It is closely linked to metabolic syndrome features such as obesity and type 2 diabetes mellitus.

     

    MASLD is characterized by the accumulation of fat in the liver and encompasses various disease stages, ranging from simple lipid buildup or steatosis (metabolic dysfunction-associated steatotic liver, MASL) to its inflammatory form known as metabolic dysfunction-associated steatohepatitis (MASH).

     

    In some instances, persistent MASH can lead to cirrhosis (liver scarring), liver failure, and liver cancer. According to a 2022 report by the World Health Organization, obesity and overweight, which are significant independent risk factors for MASLD, affect nearly 60% of adults and approximately one in three children in Europe.

  • Due to its increasing prevalence, MASLD has become the most common reason for liver transplantation and the primary cause of liver cancer. From a clinical standpoint, the challenge lies in identifying which MASLD patients will progress to cirrhosis, end-stage liver disease, or liver cancer, in order to provide appropriate care.

     

    Currently, the diagnosis of MASLD necessitates an invasive liver biopsy procedure, limited to specialized hospitals, highlighting the need for improved non-invasive diagnostic tools.

  • Biomarkers such as NordicPRO-C3™, PRO-C6, and CTX-III provide a non-invasive way to assess liver fibrosis by measuring collagen turnover in the blood. These markers help monitor disease progression, evaluate treatment response, and identify patients at higher risk for advanced fibrosis or MASH.

  • NordicPRO-C3™ measures active fibrogenesis and is supported by the FDA as a biomarker for liver disease. It is particularly useful for identifying patients with advanced fibrosis (F3–F4) and has been used as a secondary endpoint in multiple antifibrotic clinical trials.

  • Yes, biomarkers like NordicPRO-C3™ are used for patient selection, endotyping, and tracking treatment efficacy. The ADAPT algorithm, which includes PRO-C3, outperforms traditional scores (e.g., FIB-4, NFS) in identifying advanced fibrosis, making it a valuable tool in MASLD clinical research.B

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