Background & aims: Progressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical...
July 10, 2021
Journal:
JHEP Rep
Author:
Erhardtsen E, Rasmussen DGK, Frederiksen P, Leeming DJ, Gluud LL, Karsdal MA, Aithal GP, Shattenberg JM, Shevell DE
Objective: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Ind...
May 27, 2021
Journal:
Gut
Author:
Mozes EF, Lee AJ, Selvaraj AE, Jayaswal ANA, Trauner M, Boursier J, Fournier C, Staufer K, Stauber ER, Younes R, Gaia S, Lupsor-Platon M, Petta S, Shima T, Okanoue T, Mahadeva S, Eddowes PJ, Hirschfield MG, Newsome NP, Wong Wai-Sun V, Chan Wah-Keong, de Ledinghen V, Fan J, Shen F, Cobbold FJ, Kim W, Lee SM, Wiegand J, Karlas T, Yilmaz Y, Palaniyappan N, Cassinotto C, Aggarwal S, Garg H, Ooi JG, Nakajima A, Yoneda M, Ziol M, Barget N, Geier A, Tuthill T, Brosnan JM, Anstee MQ, Neubauer S, Harrison AS, Bossuyt MP, Pavlides M, Aithal GP, Bugianessi E
Background and aims: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alc...
May 13, 2021
Journal:
J Hepatol
Author:
Selvaraj AE, Mozes EF, Jayaswal ANA, Zafarmand HM, Vali Y, Lee AJ, Levick KC, Young AJL, Palaniyappan N, Romero-Gomez M, Brosnan JM, Tuthill AT, Anstee MQ, Neubauer S, Harrison AS, Bossuyt MP, Pavlides M, Aithal GP, Chang-Hai L
Background: Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD); no approved therapies for NASH currently exist. Pegbelfermin (PGBF), a human fibroblast growth factor 21 analog, has metabolic effects that may provide benefit for patients with NASH....
February 28, 2021
Journal:
Contemp Clin Trials
Author:
Abdelmalek MF, Charles ED, Sanyal JA, Harrison AS, Neuschwander-Tetri BA, Goodman Z, Ehman RA, Karsdal MA, Nakajima A, Du S, Tirucherai GS, Klinger GH, Mora J, Yamaguchi M, Shevell DE, Loomba R
There is an unmet need for high-quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non-alcoholic fatty liv...
April 9, 2020
Journal:
Liver Int
Author:
Karsdal MA, Daniels SJ, Nielsen SH, Bager CL, Rasmussen DGK, Loomba R, Surabattula R, Villesen IF, Luo Y, Gudmann NS, Nielsen MJ, George J, Christian R, Leeming DJ, Schuppan D, Shevell DE
Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. The overlap between ALD and NAFLD suggests the existence of metabolic steatohepatitis. Development of in vivo models that reflect various aspects of human steatohepatitis is essenti...
January 6, 2020
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Daniels SJ, Leeming DJ, Detlefsen S, Bruun MF, Hjuler ST, Henriksen K, Hein P, Krag A, Karsdal MA, Nielsen MJ, Brockbank S, Cruwys S
BACKGROUND: Lifestyle modifications remain the cornerstone of treatment in non-alcoholic fatty liver disease (NAFLD). However, they requently fail related to the inability of patients to implement lasting changes. AIMS: To evaluate the effects of a short, web-based, individualised exercise program ...
October 16, 2019
Journal:
Aliment Pharmacol Ther.
Author:
Huber Y, Pfirrmann D, Gebhardt I, Labenz C, Gehrke N, Straub C, Ruckes C, Bantel H, Belda E, Clément K, Leeming DJ, Karsdal MA, Galle PR, Simon P, Schattenberg JM
There is an unmet need for non-invasive biomarkers in non-alcoholic fatty liver disease (NAFLD) that can diagnose advanced disease and identify patients suitable for clinical trials. The PRO-C3 collagen neo-epitope is a putative direct marker of fibrogenesis. We assessed the performance of PRO-C3 in...
July 4, 2019
Journal:
JHEP Rep
Author:
Boyle M, Schattenberg JM, Ratziu V, Bugianessi E, Petta S, Oliveira CP, Govaere O, Yournes R, McPherson S, Bedossa P, Nielsen MJ, Kendrick, Anstee QM, Karsdal MA, Tiniakos D, Leeming DJ
BACKGROUND AND AIM: Given the high global prevalence of non-alcoholic fatty liver disease (NAFLD), the need for relevant non-invasive biomarkers and algorithms to accurately stage disease severity is a critical unmet medical need. Identifying those with advanced fibrosis (≥F3) is the most crucial, a...
July 16, 2018
Journal:
Hepatology
Author:
Daniels SJ, Leeming DJ, Eslam M, Hashem AM, Nielsen MJ, Krag A, Karsdal MA, Grove JI, Guha IN, Kawaguchi T, Torimura T, McLeod D, Akiba J, Kaye P, de Boer B, Aithal GP, Adams LA, George J
Background and aims: Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human ...
July 3, 2015
Journal:
Dig Dis Sci
Author:
Nielsen MJ, Lehmann J, Leeming DJ, Schierwagen R, Klein S, Jansen C, Strassburg CP, Bendtsen F, Møller S, Sauerbruch T, Karsdal MA, Krag A, Trebicka JK
Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential...
May 15, 2015
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Karsdal MA, Manon-Jensen T, Genovese F, Kristensen JH, Nielsen MJ, Brandt-Hansen NU, Bay-Jensen AC, Bager CL, Krag A, Krarup H, Leeming DJ, Schuppan D, Blanchard AD, Bülow Sand JM
Aim: Liver fibrosis involves excessive remodeling and deposition of fibrillar extracellular matrix (ECM) components, which leads to malfunction of the organ, causing significant morbidity and mortality. The aim of this study was to assess whether levels of a type V collagen fragment, the propeptide ...
August 16, 2011
Journal:
Biomarkers
Author:
Vassiliadis E, Veidal SS, Simonsen H, Larsen DV, Vainer B, Chen X, Zheng Q, Karsdal MA, Leeming DJ
Background and aims: During fibrogenesis, in which excessive remodeling of the extracellular matrix occurs, both the quantity of type VI collagen and levels of matrix metalloproteinases, including MMP-2 and MMP-9, increase significantly. Proteolytic degradation of type VI collagen into small fragmen...
June 9, 2011
Journal:
PLoS One
Author:
Veidal SS, Karsdal MA, Vassiliadis E, Nawrocki A, Larsen MR, Nguyen QH, Hägglund P, Luo Y, Zheng Q, Vainer B, Leeming DJ
OBJECTIVES: Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation. DESIGN AND METHODS: A monoclonal antibody targeting a spec...
July 10, 2010
Journal:
Clin Biochem
Author:
Barascuk N, Veidal SS, Larsen L, Larsen DV, Larsen MR, Wang J, Zheng Q, Xing R, Cao Y, Rasmussen LM, Karsdal MA
BACKGROUND: Fibrosis can be described as the excess deposition of extracellular matrix (ECM) components, such as collagens and proteoglycans. Fibrosis of the liver, which eventually leads to cirrhosis, is a major global health problem. Being able to measure fibrosis progression may enable timely pre...
April 1, 2010
Journal:
Fibrogenesis Tissue Repair
Author:
Veidal SS, Vassiliadis E, Bay-Jensen AC, Tougas G, Vainer B, Karsdal MA
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