Collagen biology and non‐invasive biomarkers of liver fibrosis

Karsdal, Morten A.; Daniels, Samuel Joseph; Nielsen, Signe Holm; Bager, Cecilie L.; Rasmussen, Daniel Guldager Kring; Loomba, Rohit; Surabattula, Rambabu; Villesen, Ida; Luo, Yang; Shevell, Diane E.; Gudmann, N.S.; Nielsen, Mette Juul; George, Jacob; Christian, Rose; Leeming, Diana Julie; Schuppan, Detlef

doi:10.1111/liv.14390

Cited by 122 publications

(123 citation statements)

References 137 publications

(259 reference statements)

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“…5A). The typical characteristics of hepatic fibrosis are the activation of HSC and excessive deposition of ECM 3 . As a unique marker of HSC activation, a-SMA is positively correlated with proliferation of HSCs and degree of liver fibrosis [28].…”

Section: Discussionmentioning

confidence: 99%

“…Studies show that the common pathological basis of many chronic liver diseases is liver fibrosis [2]. Liver fibrosis is an intermediate process of transformation from a variety of chronic liver diseases to liver cirrhosis, which is mainly characterized by the activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix (ECM) [3,4]. However, ideal drugs for the treatment of liver fibrosis are lacking.…”

Section: Introductionmentioning

confidence: 99%

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Erythropoietin-Modified Mesenchymal Stem Cells Enhance Anti-fibrosis Efficacy in Mouse Liver Fibrosis Model

Wang

et al. 2020

Tissue Eng Regen Med

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BACKGROUND: Mesenchymal stem cell (MSC)-based cell transplantation is an effective means of treating chronic liver injury, fibrosis and end-stage liver disease. However, extensive studies have found that only a small number of transplanted cells migrate to the site of injury or lesion, and repair efficacy is very limited. METHODS: Bone marrow-derived MSCs (BM-MSCs) were generated that overexpressed the erythropoietin (EPO) gene using a lentivirus. Cell Counting Kit-8 was used to detect the viability of BM-MSCs after overexpressing EPO. Cell migration and apoptosis were verified using Boyden chamber and flow cytometry, respectively. Finally, the anti-fibrosis efficacy of EPO-MSCs was evaluated in vivo using immunohistochemical analysis. RESULTS: EPO overexpression promoted cell viability and migration of BM-MSCs without inducing apoptosis, and EPO-MSC treatment significantly alleviated liver fibrosis in a carbon tetrachloride (CCl 4) induced mouse liver fibrosis model. CONCLUSION: EPO-MSCs enhance anti-fibrotic efficacy, with higher cell viability and stronger migration ability compared with treatment with BM-MSCs only. These findings support improving the efficiency of MSCs transplantation as a potential therapeutic strategy for liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Erythropoietin-Modified Mesenchymal Stem Cells Enhance Anti-fibrosis Efficacy in Mouse Liver Fibrosis Model

Wang

et al. 2020

Tissue Eng Regen Med

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“…Other direct markers of liver fibrosis are collagens and their fragments since they represent the principal component of the fibrotic scars. The most validated biomarkers for the measurement of type III collagen formation are the amino-terminal propeptide of procollagen type III (PIIINP) and N-terminal pro-collagen III peptide (PRO-C3) biomarkers[ 46 ]. PRO-C3 which is a collagen fragment is significantly higher in NASH patients with advanced fibrosis than those without advanced fibrosis.…”

Section: Evaluation Of Liver Fibrosis In Nafldmentioning

confidence: 99%

Clinical assessment and management of liver fibrosis in non-alcoholic fatty liver disease

Campos-Murguía

Ruiz-Margáin

González-Regueiro

et al. 2020

WJG

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Non-alcoholic fatty liver disease (NAFLD) is among the most frequent etiologies of cirrhosis worldwide, and it is associated with features of metabolic syndrome; the key factor influencing its prognosis is the progression of liver fibrosis. This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD, analyzing the currently available literature. In the assessment of NAFLD patients, it is important to identify clinical, genetic, and environmental determinants of fibrosis development and its progression. To properly detect fibrosis, it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores, followed by a complementary imaging study (transient elastography, magnetic resonance elastography or acoustic radiation force impulse) and finally a liver biopsy, when needed. To help with the selection of the most appropriate method a Fagan′s nomogram analysis is provided in this review, describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis. Finally, treatment should always include diet and exercise, as well as controlling the components of the metabolic syndrome, +/- vitamin E, considering the presence of sleep apnea, and when available, allocate those patients with advanced fibrosis or high risk of progression into clinical trials. The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD, aiming to decrease/stop its progression and improve their prognosis.

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“…Apart from being invasive, the liver biopsy also have several limitations including, patient discomfort, considerable cost of treatment, prolonged hospitalizations and minimal risk of complications such as peritoneal bleeding. Furthermore, there may be sampling variation, poor sample quality, inter- and intra-observer variability and the possibility of error in small biopsy samples which may not reflect the fibrotic changes occurring in the entire liver [ 22 , 23 , 24 , 26 ]. Therefore, alternate strategies are required to supplant liver biopsy since it is not practical and affordable to biopsy each patient.…”

Section: Introductionmentioning

confidence: 99%

Elucidating Potential Profibrotic Mechanisms of Emerging Biomarkers for Early Prognosis of Hepatic Fibrosis

Zehra

Curry

Pillai

et al. 2020

IJMS

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Hepatic fibrosis has been associated with a series of pathophysiological processes causing excessive accumulation of extracellular matrix proteins. Several cellular processes and molecular mechanisms have been implicated in the diseased liver that augments fibrogenesis, fibrogenic cytokines and associated liver complications. Liver biopsy remains an essential diagnostic tool for histological evaluation of hepatic fibrosis to establish a prognosis. In addition to being invasive, this methodology presents with several limitations including poor cost-effectiveness, prolonged hospitalizations, and risks of peritoneal bleeding, while the clinical use of this method does not reveal underlying pathogenic mechanisms. Several alternate noninvasive diagnostic strategies have been developed, to determine the extent of hepatic fibrosis, including the use of direct and indirect biomarkers. Immediate diagnosis of hepatic fibrosis by noninvasive means would be more palatable than a biopsy and could assist clinicians in taking early interventions timely, avoiding fatal complications, and improving prognosis. Therefore, we sought to review some common biomarkers of liver fibrosis along with some emerging candidates, including the oxidative stress-mediated biomarkers, epigenetic and genetic markers, exosomes, and miRNAs that needs further evaluation and would have better sensitivity and specificity. We also aim to elucidate the potential role of cardiotonic steroids (CTS) and evaluate the pro-inflammatory and profibrotic effects of CTS in exacerbating hepatic fibrosis. By understanding the underlying pathogenic processes, the efficacy of these biomarkers could allow for early diagnosis and treatment of hepatic fibrosis in chronic liver diseases, once validated.

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Collagen biology and non‐invasive biomarkers of liver fibrosis

Cited by 122 publications

References 137 publications

Erythropoietin-Modified Mesenchymal Stem Cells Enhance Anti-fibrosis Efficacy in Mouse Liver Fibrosis Model

Erythropoietin-Modified Mesenchymal Stem Cells Enhance Anti-fibrosis Efficacy in Mouse Liver Fibrosis Model

Clinical assessment and management of liver fibrosis in non-alcoholic fatty liver disease

Elucidating Potential Profibrotic Mechanisms of Emerging Biomarkers for Early Prognosis of Hepatic Fibrosis

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