Author: Claire Hornung

NordicPRO-C3™ and NordicPRO-C6™ in Connective Tissue Disease-Associated Interstitial Lung Disease

Posted on by Claire Hornung

NordicPRO-C3™ and nordicPRO-C6™ fibrogenesis biomarkers in connective tissue disease-associated interstitial lung disease: results from the phase IIb RECITAL trial

Introduction

ILD is a major cause of morbidity and mortality in connective tissue disease (CTD). Cyclophosphamide is an effective treatment for CTD-ILD, but limited by side effects. In this study, we additionally tested rituximab as an alternative in the RECITAL phase IIb trial. Both drugs improved the lung function with rituximab showing fewer adverse events (Maher, 2022. Lancet Resp Med)

Poster

ATS2025_Interstitial_Lung_Disease_Nordic BioscienceDownload

Conclusion

The decrease in nordicPRO-C3™ and nordicPRO-C6™ suggest that, besides their immunomodulatory effects, these drugs may also reduce fibrogenesis. Both biomarkers, measured at baseline and as % change from baseline, are associated with FVC response. These findings highlight nordicPRO-C3™ and nordicPRO-C6™ as promising biomarkers for progressive CTD-ILD.

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    Identifying Patients with Mild-Stage Emphysema in COPD via Machine Learning

    Posted on by Claire Hornung

    Identifying biomarkers of mild-stage emphysema in COPD patients via interpretable machine learning

    Introduction

    Emphysema results from alveolar damage—causing abnormal extracellular matrix (ECM) remodeling and impaired lung function. Early detection in mild, often asymptomatic stages is key to timely intervention. Although computed tomography (CT) scans are the most accurate detection method, pathological changes may occur before emphysema becomes visible, highlighting the need for non-invasive early detection approaches.

    This study aimed to develop a proof-of-concept machine learning (ML) pipeline to identify patients with mild-stage emphysema using circulating biomarkers.

    Poster

    ATS2025_Mild-stage_Emphysema_Nordic BioscienceDownload

    Conclusion

    ML demonstrates potential for early-stage emphysema diagnosis through biomarker-driven methods. Quantifying fragments of ECM remodeling—driven by immune cell activity and collagen formation—could potentially serve as early diagnostic biomarkers in patients without lung function decline.

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      Tankyrase Inhibitor OM153 Exhibits Anti-Fibrotic Effects in a Scar-in-a-Jar Pulmonary Fibrosis Model

      Posted on by Claire Hornung

      Introduction

      Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic and fatal lung disease with limited
      treatment options. Fibroblast activation and ECM deposition is pivotal in development of IPF, thus
      inhibiting fibrogenesis and ECM deposition is crucial for anti-fibrotic approaches to treat IPF.

      This study aims to prove that tankyrase inhibition reduces fibrogenesis induced by a fibrotic cocktail (FC) in primary human lung fibroblasts derived from IPF patients and decreases extracellular matrix biomarkers nordicPRO-C3™ and nordicPRO-C6™.

      Poster

      ATS2025_Tankyrase_Inhibitor_OM153_Nordic BioscienceDownload

      Conclusion

      These findings highlight the potential of tankyrase inhibiton as a therapeutic target for IPF and
      support the use of the Scar–in-a-Jar model as an effective tool for IPF drug screening.

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        Engineering Liver Fibrosis in a Three-Dimensional, ECM-Hydrogel Disease Model

        Posted on by Claire Hornung

        Engineering liver fibrosis in a three-dimensional, extracellular matrix-hydrogel disease model

        Introduction

        Modeling fibrosis requires replicating the mechano-chemical cues of the extracellular matrix (ECM), including binding sites, three-dimensionality, and biomechanics. To engineer a liver fibrosis model based on native, decellularized ECM with spatial and compositional integrity, layered on a hydrogel of poly(ethylene glycol) diacrylate (PEGDA) that provides tunable mechanical properties.

        This model aims to support cell recolonization and facilitate the investigation of cell-matrix interactions, fibrogenic remodeling, and therapeutic screening in a physiologically relevant context.

        Poster

        EASL2025_ECM_Hydrogel_Model_Nordic BioscienceDownload

        Conclusion

        HSCs colonize porcine liver ECM and synthesize new collagen. Biochemical signaling and biomechanical properties drive ECM deposition, recapitulating key features of the fibrotic niche. Upon treatment with relaxin-2, HSCs display an ECM-degrading activity. The ECM-hydrogel constructs exhibit no cytotoxicity, and polymer concentration can be tuned to modulate the mechanical properties of the ECM. Due to its anatomical similarity to human tissue, porcine ECM offers a biologically relevant scaffold for in vitro fibrosis modeling without the ethical concerns associated with live animal use.

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          Bile Acids Drive Fibroblast Activation and Fibrogenesis in PSC

          Posted on by Claire Hornung

          Bile acids drive fibroblast activation, fibrogenesis, interstitial matrix fibrosis and outcomes in PSC

          Introduction

          Fibrosis often originates from a persistent insult that damages epithelial and endothelial cells and activates chronic pro-inflammatory processes that impair the regular course of tissue repair.

          A hallmark of fibrosis is the activation of fibroblasts leading to excessive production of type I, III, and VI collagens in the interstitial space of the extracellular matrix (ECM). Several drivers, including transforming growth factor-beta (TGF-β), have been identified as key drivers of fibroblast activation. While bile acids (BA) have been shown to correlate with the fibroblast activation marker nordicPRO-C3™ in biliary diseases, their precise role in the process of fibrogenesis remains unclear.

          The present work aims to investigate the relationship between bile acids and markers of ECM formation and degradation during anti-fibrotic therapy (an engineered FGF-19; NCT02704364 analogue;) and related prognostic ability of biomarkers reflecting fibroblast activity in PSC.

          Poster

          ASL2025_Bile_Acids_In_PSC_Nordic BioscienceDownload

          Conclusion

          Fibroblast activation and collagen formation play a crucial role in determining outcomes in PSC. The data suggests that bile acids activate fibroblast driving fibrogenesis, and that lowering of bile acids attenuate the fibrotic drive. Lowering fibroblast activity may have positive effects on liver related outcomes in PSC.

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            Weight Dependent, Weight Independent and Non-Pharmacological Effects on Fibroblast Activity in MASLD

            Posted on by Claire Hornung

            Weight dependent, weight independent and non-pharmacological effects on fibroblast activity in metabolic dysfunction associated steatotic liver disease (MASLD)

            Introduction

            It is well established that fibroblasts are activated by metabolic dysfunction and are a central component of liver function decline and death. Fibroblast activities, both type III and type VI collagen formation, have been shown to be highly prognostic for outcome of liver, heart and kidney related events in MAFLD populations. Fibroblast activity in man, may both be inhibited by weight dependent and independent
            mechanisms, and as such monitoring fibroblast activities is essential.

            Poster

            EASL2025_Fibroblast_Activity_MASLD_Nordic BioscienceDownload

            Conclusion

            Pharmacological and non-pharmacological induction of weight loss results in different deactivation of fibroblasts activities, which may have divergent efficacy on heart and liver related outcomes. Furthermore, weight dependent and independent mechanisms of deactivation fibroblasts may result in additional effects on bone and muscle. This understanding may be needed when designing the optimal intervention strategy, including possible combination regimens, for the individual MAFLD patient.

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              PRO-C4 Is Related to Cardiometabolic Risk Factors, Steatosis, and Liver Stiffness

              Posted on by Claire Hornung

              PRO-C4, a biomarker of perisinusoidal fibrosis, is related to cardiometabolic risk factors, steatosis, and liver stiffness

              Introduction

              A histological characteristic of early liver damage is the formation of perisinusoidal fibrosis with thickening of the hepatocyte basement membrane. Type IV collagen is a key component of the basement membrane of the extracellular matrix and can be assessed serologically by the biomarker PRO-C4. Thus, PRO-C4 could potentially reflect early features of liver damage in patients with early-stage SLD.

              In this study we aimed to explore whether basement membrane remodeling assessed systemically was related to risk factors of chronic liver disease including Met S, liver steatosis assessed by CAP and liver
              stiffness by Fibroscan.

              Poster

              EASL2025 PRO-C4_Nordic BioscienceDownload

              Conclusion

              Elevated PRO-C4 is associated with presence of cardiometabolic risk factors and LSM>8kpa. PRO-C4 potentially reflects perisinusoidal fibrosis from early liver damage and repair due to its relation to increasing degree of steatosis. Furthermore, PRO-C4 was also related to elevated liver stiffness in a population at risk of SLD.

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                NordicPRO-C3™ and Liver Stiffness Correlate with Collagen Distribution in MASLD and ALD

                Posted on by Claire Hornung

                Fibroblast Activity (PRO-C3) and Liver Stiffness Correlate with spatial distribution of Collagens in MASLD and ALD: Insights from Digital Pathology

                Introduction

                In patients with metabolic dysfunction associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) Kleiner fibrosis stage provides limited information on the spatial distribution of collagen in the liver. Digital pathology provides a more advanced assessment of collagen localization; however, there is limited knowledge linking non-invasive tests to the spatial distribution of collagen.

                In this study we aimed to explore the ability of digital pathology by second harmonic generation to evaluate fibrosis in ALD and MASDL as well as investigate the correlation between the spatial distribution of collagens and fibroblast activity (nordicPRO-C3™).

                Poster

                EASL2025 PRO-C3 in ALD and MASLD_Nordic BioscienceDownload

                Conclusion

                Correlations between spatial distribution of collagens and systemically assessed active fibrogenesis and liver stiffness in both MASLD and ALD. While similarities and differences were observed. The correlations were potentially influenced by etiology however also sample size. In conclusion, these findings underscore the connection between biopsy-based digital pathology assessments and non-invasive tests
                for liver fibrosis.

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                  NordicPRO-C6™/Platelet Count Score Is Prognostic for Liver-Related Outcomes in CHC

                  Posted on by Claire Hornung

                  A composite score of PRO-C6 and platelet count is prognostic for liver-related outcomes in patients with chronic hepatitis C

                  Introduction

                  There is a need to identify prognostic markers for patients with chronic liver disease at increased risk of developing a liver-related outcome. NordicEndotrophin™, a signal peptide that is a driver of fibroblast
                  activation and promotion of fibroinflammatory disease, can be assessed using the nordicPRO-C6™ assay.
                  Our aim was to explore the diagnostic utility of a composite score of nordicPRO-C6™/Platelets to predict liver-related outcomes in The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial (HALT-C).

                  Poster

                  EASL2025_PRO-C6 in CHC_Nordic BioscienceDownload

                  Conclusion

                  A composite score combining nordicPRO-C6™ and platelet count has been shown to improve the prognosis of liver-related outcomes in patients with chronic hepatitis C (CHC) cirrhosis compared to nordicPRO-C6™ or platelet count alone. Notably, among CHC patients with cirrhosis, those classified in the low-score group experienced no liver-related outcomes for more than two years. This nordicPRO-C6™/platelet count composite score may therefore offer a more effective tool for risk stratification in CHC patients with advanced liver disease. However, further validation is needed to confirm its prognostic value in CHC patients following sustained virologic response (SVR), as well as in individuals with other forms of advanced-stage chronic liver disease.

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                    Hot & Cold Fibrosis: Fibro-Inflammatory Biomarkers as Prognostic Tools in ALD

                    Posted on by Claire Hornung

                    Hot & cold fibrosis: fibro-inflammatory biomarkers as prognostic tools in alcohol-related liver disease

                    Introduction

                    Alcohol overuse can trigger liver inflammation, which may progress to fibrosis and cirrhosis—stages within the spectrum of alcohol-related liver disease (ALD). The combination of fibrotic and inflammatory processes drives the course of ALD progression and influences the risk of clinical outcomes. The new concept of “hot & cold fibrosis” – defined by the presence (hot) or absence (cold) of immune cells within fibrotic tissues – can help to understand the degree of inflammation associated with liver fibrosis and its impact in ALD progression.

                    This study aims to investigate how immune cell activity biomarkers can improve the prognostic performance of fibrogenesis biomarkers with established prognostic value for risk stratification in ALD.

                    Poster

                    EASL2025 Hot&Cold_Fibrosis_Nordic BioscienceDownload

                    Conclusion

                    ALD patients at higher risk of clinical outcomes are characterized by increased fibrogenesis and increased
                    inflammation. Combining biomarkers reflecting different biological processes improved the prognostic performance of individual biomarkers and may aid in selecting personalized treatment based on distinct patient profiles.

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