NordicPRO-C3™ as a Predictor of Liver Related Outcomes in Chronic Hepatitis C

PRO-C3 determined active fibrogenesis is a predictor of liver-related outcomes in patients with chronic hepatitis C

Introduction

Patients with untreated chronic hepatitis C (CHC) infection are at increased risk of developing a liver related outcome. Despite the availability of simplified direct-acting antiviral therapy, the prevalence of CHC remains unchanged in many industrialized countries. Biomarkers that can predict which chronic liver disease patients with inflammatory injury are at greatest risk of developing a clinical outcome are required. In this study we aim to investigate the ability of nordicPRO-C3™ as a marker of active fibrogenesis to predict liver-related outcomes compared to METAVIR fibrosis stage on biopsy in patients with hepatitis C.

Poster

Conclusion

We conclude that fibrosis activity (nordicPRO-C3™) is associated with an increased risk of developing a liver-related outcome in patients with untreated HCV infection. NordicPRO-C3™ provides a higher risk predictor for outcomes than METAVIR fibrosis stage on biopsy. A pro-fibrogenic marker such as nordicPRO-C3™ could provide prognostic utility in other chronic liver disease patients with ongoing inflammatory injury.

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    NordicPRO-C6™ Is Prognostic for Liver-Related Events in CHC Patients with Cirrhosis

    Fibroblast activity kills – Circulating endotrophin (PRO-C6) is prognostic for liver-related events in patients with cirrhosis from chronic hepatitis C

    Introduction

    Prognostic markers for patients with compensated cirrhosis at increased risk of developing liver-related events are required. Endotrophin, a potential driver of fibroblast activation and mediator of fibroinflammatory disease, may be assessed non-invasively using nordicPRO-C6™. Blood-based collagen extracellular matrix remodeling markers may provide novel prognostic information to identify patients with cirrhosis at higher risk of developing a liver-related event.

    In this study we aimed to investigate the ability of nordicPRO-C6™ to predict liver-related events in The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial (HALT-C) (ClinicalTrials.gov #NCT00006164).

    Poster

    Conclusion

    NordicPRO-C6™, a biomarker of circulating endotrophin, was primarily associated with an increased risk of developing a liver-related event in patients with cirrhosis from CHC. NordicPRO-C6™ is a potential monitoring blood-based marker that may also provide prognostic information in treatment-naïve CHC patients with moderate-advanced fibrosis at higher risk of developing a liver-related event. The prognostic utility of nordicPRO-C6™ in CHC patients after sustained virologic response and other advanced stage chronic liver disease is required.

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      Endotrophin as an Early Marker of Kidney Outcomes in Type 2 Diabetes

      Endotrophin as an early marker of kidney outcomes in persons with type 2 diabetes: Findings from the PROVALID study

      Introduction

      Diabetic kidney disease (DKD) is driven by pathophysiological processes, including fibrosis. NordicEndotrophin™ (ETP), a pro-fibrotic fragment generated during collagen type VI formation, has previously been shown to be a biomarker of DKD progression1,2,3,4,5. The aim of this study was to investigate, for the first time, circulating ETP as a risk marker for kidney outcomes in persons with type 2 diabetes (T2D) being taken care of at the primary level of healthcare.

      Poster

      Conclusion

      Plasma ETP (nordicEndotrophin™) has been identified as an independent risk marker for kidney outcomes in individuals with type 2 diabetes (T2D) with early-stage kidney disease. Higher levels of ETP were associated with a significantly increased risk of developing the kidney endpoint in persons with eGFR >90 ml/min/1.73 m2. These findings demonstrate that markers of fibrosis, such as ETP, may serve as early markers for kidney disease progression or kidney failure in persons with T2D and apparently normal kidney function.

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        LG1M Is Prognostic for Long-Term Readmission After AKI

        The novel fibrosis biomarker LG1M is prognostic for long-term readmission after AKI

        Introduction

        Acute Kidney Injury (AKI), survivors are at increased risk of long-term adverse outcomes, including readmission to hospital. Pathophysiological consequences of AKI, include extracellular matrix (ECM) remodeling. Tools to monitor the long-term health risk of patients after AKI are needed to improve
        patient outcome.

        Poster

        Conclusion

        Circulating levels of LG1M were elevated in AKI patients 1 year after the AKI episode and correlated with markers of kidney function in the AKI group and to a lower extent in the CKD control group. In the AKI group, LG1M was associated with the risk of readmission, even though the significance of the association was lost in adjusted analyses. This biomarker, quantifying circulating levels of a laminin fragment, may reflect injury to the basement membrane (of which laminin is a major component) after AKI, which was associated with an increased risk of worse outcome in patients that experienced an episode of AKI.

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          Advancing Diagnostic Precision of Emphysema COPD

          Machine-learning classification integrating non-invasive biomarkers, clinical characteristics and pulmonary function

          Introduction

          Computed tomography (CT) is used for evaluating phenotypic abnormalities in chronic obstructive
          pulmonary disease (COPD), yet its cost and time-intensive nature limit routine use. Developing an
          easily implementable technique for classifying emphysema extent is thus essential.

          This study aimed to develop a diagnostic model to classify emphysema extent in COPD
          patients relying solely on easily obtained measures such as clinical characteristics and
          non-invasive biomarkers.

          Poster

          Conclusion

          Diagnostic models incorporating easily obtainable measures effectively distinguished COPD patients with high emphysema extent from those with low extent. Such models for classifying emphysema patterns have the potential for clinical implementation, aiding in diagnosis or serving as a decision-making tool to determine the necessity of further CT scans.

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            Data-Driven Comorbidity Profiles in COPD

            Data-driven identification and investigation of comorbidity profiles in patients with chronic obstructive pulmonary disease: a multicohort study

            Introduction

            Comorbidities are common in chronic obstructive pulmonary disease (COPD), adversely affecting
            patients’ quality of life and their disease trajectories. While previous studies have predominantly
            examined individual comorbidities, there has been limited exploration of their coexistence.

            This study aimed to identify comorbidity clusters among real-world cohorts of COPD patients using machine learning techniques, and to investigate clinical characteristics and mortality within these clusters.

            Poster

            Conclusion

            This study confirms distinct comorbidity clusters in two well-characterized cohorts of patients with COPD which can be linked to different patient subgroups. In a broad COPD patient population, comorbidity profiles could hold prognostic relevance. The findings of this study enhance the understanding of the comorbidity landscape in COPD and highlights the importance of comorbidity assessment in clinical management.

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              PRO-C11 and PRO-C16 Are Markers of Intestinal Fibrosis – Results from the ImageKids Study

              PRO-C11 and PRO-C16 are markers of intestinal fibrosis and are associated with MRE-confirmed intestinal strictures – Results from the ImageKids study

              Introduction

              Intestinal fibrosis and strictures is one of the most challenging complications in patients with
              Crohn’s disease (CD). There is an urgent medical need for non-invasive serological biomarkers for intestinal fibrosis, as magnetic resonance enterography (MRE) is not a feasible tool for repeated
              monitoring.

              In this study we investigated Protein FingerprintAssays (PFA) biomarkers of collagen formation,
              PRO-C11 (formation of type XI collagen), and PRO-C16 (formation of type XVI collagen) in serum from pediatric CD (pCD).

              Poster

              Conclusion

              Based on these biomarker data from the ImageKids study, PRO-C11 and PRO-C16 demonstrate potential as important non-invasive biomarkers reflecting intestinal fibrosis and stenosis.

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                CPa9-HNE Can Monitor Endoscopic and Clinical Disease Activity in Ulcerative Colitis

                CPa9-HNE: A neutrophil-derived fragment of calprotectin measured in serum can monitor endoscopic and clinical disease activity in ulcerative colitis

                Introduction

                Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) presenting in remitting ulcerations of the colonic mucosa and submucosa. Mucosal healing is therefore an important treatment target for optimal disease management. Fecal calprotectin is commonly used to monitor mucosal healing –
                however, patient compliance is low due to a preference for serological markers.

                In this study we aimed to investigate the association of serum calprotectin [CPa9-HNE], a non-invasive neo-epitope biomarker of true neutrophil activity, with both clinical and endoscopic disease activity in UC.

                Poster

                Conclusion

                CPa9-HNE accurately reflected both clinical and endoscopic disease activity in ulcerative colitis, based on the UCEIS and full Mayo score. These findings highlight the potential use of CPa9-HNE as a non-invasive tool to monitor both endoscopic and clinical disease activity in UC, with the potential of guiding treatment decisions and better aligning with patient preferences.

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                  Single Joint Tissue Destruction Biomarkers

                  Single joint tissue destruction biomarkers: association between type III collagen degradation and local tissue damage of a single joint

                  Introduction

                  The landscape of osteoarthritis (OA) research and therapeutic development has undergone significant transformation, shifting from a primarily structural focus to an emphasis on patient-reported outcomes (PROs). Pain, which primarily originates from the soft tissue of the joint, is intricately linked with the structural integrity of joint tissues. Serological biomarkers are considered potential surrogate endpoints, but their contribution from single joints to systemic levels in OA patients is unclear.

                  This study explored systemic biomarker levels’ response to tissue damage and healing in patients undergoing knee or hip joint replacement revision for aseptic failure, compared to patients with chronic pain from a joint replacement, but not receiving surgery.

                  Poster

                  Conclusion

                  C3M degradation was found to increase in response to tissue insult to the joint from revision surgery, while no change was observed in a non-surgical group with chronic pain of the joint over 6 months. The increase and gradual decrease throughout the study period indicate a relationship between systemic levels of type III collagen degradation fragments and soft-tissue destruction and inflammation of the joint.

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                    Weight Loss Lead to Significant Effects on OA Pain and Function: Do the Benefits Outweigh the Risks?

                    Introduction

                    Drug development in the osteoarthritis (OA) field has proven extremely difficult, with a discordance between joint structure and pain. Weight loss has been associated with an effect on pain and function. Several molecular endotypes have been suggested for OA, which could be treatable, such as bone, inflammation, and lately, an overweight endotype.

                    The aim was to investigate the relationship between obesity, weight loss and patient-reported outcomes (PROs) in patients with persistent pain, and the effect on joint and bone tissue related soluble biomarkers.

                    Poster

                    Conclusion

                    Changes in PROs were significantly associated with obesity. Weight loss was associated with an increase in bone and cartilage degradation, as well as lowering in the interstitial matrix degradation. These data indicate that weight loss comes with a risk of increased joint tissue loss, but improvement in tissue inflammation.

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