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Aberrant basement membrane production by HSCs in MASLD is attenuated by the bile acid analog INT-767.

December 1, 2024

Hepatol Commun

Abstract BACKGROUND The farnesoid X receptor (FXR) is a leading therapeutic target for metabolic dysfunction-associated steatohepatitis (MASH)-related fibrosis. INT-767, a potent FXR agonist, has shown promise in preclinical models. We aimed to define the mechanisms of INT-767 activity in experimental MASH and dissect cellular and molecular targets of FXR agonism in human disease. METHODS Leptin-deficient […]

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Performance of novel collagen turnover biomarkers to detect increased liver stiffness in MASLD.

August 1, 2024

J Intern Med

Abstract BACKGROUND Cleavage products from collagen formation and degradation hold potential as first-line biomarkers for the risk of advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we evaluated the performance of PRO-C3, PRO-C6, C4M, PRO-C18L, and the clinical score ADAPT (age, diabetes, PRO-C3, and platelet count) to detect patients with an […]

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Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis.

July 1, 2024

Hepatol Commun

Abstract BACKGROUND Novel noninvasive predictors of disease severity and prognosis in primary sclerosing cholangitis (PSC) are needed. This study evaluated the ability of extracellular matrix remodeling markers to diagnose fibrosis stage and predict PSC-related fibrosis progression and clinical events. METHODS Liver histology and serum markers of collagen formation (propeptide of type III collagen [Pro-C3], propeptide […]

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Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort.

May 1, 2024

Liver Int

Abstract BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test […]

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Von Willebrand factor processing in patients with advanced chronic liver disease and its relation to portal hypertension and clinical outcome.

December 1, 2023

Hepatol Int

Abstract BACKGROUND AND AIMS Endothelial dysfunction and portal hypertension (PH) are reflected by increased von Willebrand factor antigen (VWF-Ag) levels in advanced chronic liver disease (ACLD). This study investigated VWF release and cleavage and their association with PH and clinical outcomes. METHODS Levels of VWF-Ag, VWF-N (VWF-propeptide), and VWF-A (VWF processed by the main VWF-cleaving […]

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Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study.

August 1, 2023

Lancet Gastroenterol Hepatol

Abstract BACKGROUND The reference standard for detecting non-alcoholic steatohepatitis (NASH) and staging fibrosis-liver biopsy-is invasive and resource intensive. Non-invasive biomarkers are urgently needed, but few studies have compared these biomarkers in a single cohort. As part of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) project, we aimed to evaluate the diagnostic accuracy of […]

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Machine learning algorithm improves the detection of NASH (NAS-based) and at-risk NASH: A development and validation study.

July 1, 2023

Hepatology

Abstract BACKGROUND AND AIMS Detecting NASH remains challenging, while at-risk NASH (steatohepatitis and F≥ 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning techniques, with clinical data and biomarkers to stage and grade patients with NAFLD. APPROACH AND RESULTS Learning data were […]

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Validation of scores of PRO-C3 to predict liver-related events in alcohol-related liver disease.

July 1, 2023

Liver Int

Abstract BACKGROUND AND AIMS Risk prediction in alcohol-related liver disease (ArLD) is an unmet need. We aimed to assess PRO-C3 models to predict liver-related events (LRE) in patients with a history of excessive alcohol use without an established diagnosis of chronic liver disease. METHODS A prospective cohort study of 462 patients with ArLD, split into […]

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Rifaximin-α for liver fibrosis in patients with alcohol-related liver disease (GALA-RIF): a randomised, double-blind, placebo-controlled, phase 2 trial.

June 1, 2023

Lancet Gastroenterol Hepatol

Abstract BACKGROUND Alcohol is the leading cause of liver-related mortality worldwide. The gut-liver axis is considered a key driver in alcohol-related liver disease. Rifaximin-α improves gut-barrier function and reduces systemic inflammation in patients with cirrhosis. We aimed to compare the efficacy and safety of rifaximin-α with placebo in patients with alcohol-related liver disease. METHODS GALA-RIF […]

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Quantification of extracellular matrix remodeling for the non-invasive identification of graft fibrosis after liver transplantation.

April 13, 2023

Sci Rep

Abstract Detecting patients with early post-transplant fibrosis after liver transplantation (LT) is very important. Non-invasive tests are needed to avoid liver biopsies. We aimed to detect fibrosis in liver transplant recipients (LTR) using extracellular matrix (ECM) remodeling biomarkers. ECM biomarkers for type III (PRO-C3), IV (PRO-C4), VI (PRO-C6) and XVIII (PRO-C18L) collagen formation and type […]

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