Category: Scientific Posters

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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                A Hallmark of Fibrosis Initiation and Mortality in Alcohol-Related Liver Disease

                Posted on by Claire Hornung

                Fibroblast activation assessed by PRO-C3 and PRO-C6 is associated to accumulation of key bile acids – A hallmark of fibrosis initiation and mortality in alcohol-related liver disease

                Introduction

                Alcohol-related liver disease (ALD) results from persistent liver damage due to excessive alcohol consumption. ALD promotes the disruption of bile acid homeostasis, further contributing for the development of liver fibrosis and disease progression to cirrhosis, and end-stage liver failure.

                The use of anti-fibrotic therapy has shown to simultaneously reduce bile accumulation and levels of
                fibroblast activity biomarker nordicPRO-C3™. However, the role of bile acids as drivers of fibrogenesis remains unclear. The present work aims to investigate the link between bile accumulation in ALD and fibrosis induction ALD by exploring associations between fibroblast activity biomarkers, bile acids, and clinical outcomes.

                Poster

                EASL2025 PRO-C3 and PRO-C6 in ALD_ Nordic BioscienceDownload

                Conclusion

                Increased circulating levels of toxic bile acids are associated to fibroblast activation and poor prognosis in ALD. The data presented suggests that bile acids are linked to activation of fibrogenesis and, therefore, may induce the development of liver fibrosis in ALD.

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                  Fibroblast Activity Assessed by NordicPRO-C3™ is Prognostic for Fibrosis Progression in MASH

                  Posted on by Claire Hornung

                  Fibroblast activity assessed by PRO-C3 is prognostic for fibrosis progression in MASH patients treated with insulin sensitizer MSDC-0602K during a phase IIb clinical trial

                  Introduction

                  Liver fibrosis is a dynamic process driven by hepatic stellate and other mesenchymal cells forming ECM and disrupting normal organ architecture, while releasing ECM fragments into the bloodstream. These fragments are surrogates of ECM formation that can be leveraged as fibrosis biomarkers. In this study, we measured biomarkers of collagen type III and type VI (nordicPRO-C3™ and nordicPRO-C6™) during EMMINENCE, a phase IIb clinical trial testing MSDC-0602K, an insulin sensitizer in MASH patients.

                  Poster

                  EASL2025 PRO-C3 in MASH_Nordic BioscienceDownload

                  Conclusion

                  Lower fibroblast activity (nordicPRO-C3™) at baseline was associated with achieving primary endpoint as well as fibrosis regression, while higher baseline nordicPRO-C3™ was associated with fibrosis progression. MSDC-0602K significantly reduced nordicPRO-C3™ and nordicPRO-C6™, suggesting an anti-fibrotic and pro-metabolic effect. NordicPRO-C3™ can identify MASH patients who are likely to respond to treatment and prognosticate their evolution.

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                    The Endotrophin Biomarker, NordicPRO-C6™, as a Marker for Intestinal Fibrosis in Crohn’s Disease

                    Posted on by Claire Hornung

                    Introduction

                    Crohn’s disease (CD) is a chronic inflammatory condition that often progresses to fibrostenotic complications due to imbalanced extracellular matrix (ECM) remodeling. Fibrosis, a result of excessive ECM deposition, is challenging to manage as current treatments do not prevent or reverse these processes. Diagnostic tools are limited, as endoscopy only visualizes the mucosa and imaging struggles to distinguish fibrosis from inflammation. Type VI collagen is associated with fibrogenesis and is also expressed by adipocytes which may suggest that type VI collagen could also be associated with creeping fat in CD patients with fibrostenotic structures.

                    This study aimed to evaluate the endotrophin marker, nordicPRO-C6™, and its ability to distinguish stenosing from luminal CD, predict postoperative recurrence, and correlation with histological fibrosis severity.

                    Poster

                    DDW2025 PRO-C6 in CD_Nordic BioscienceDownload

                    Conclusion

                    NordicPRO-C6™ as an ECM marker demonstrated potential in characterizing fibrosis in CD and distinguishing stenosing from luminal phenotype. Evidence from tissue samples suggested that increased collagen VI gene expression was associated with the development of complicated disease featuring strictures. NordicPRO-C6™ levels decreased following resection but returned to baseline by 3 months, which may indicate a risk of recurrent fibrosis formation. These findings highlight nordicPRO-C6™ as a promising non-invasive tool for monitoring disease stage and fibrosis. Extended follow-up studies are crucial to validate the clinical utility of nordicPRO-C6™ and to further explore its role in guiding personalized treatment strategies.

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