39 Publication(s) found
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Hepatic System
5. Sep 2018

No effect of rifaximin on soluble CD163, mannose receptor of type III and IV neoepitope collagen markers in decompensated cirrhosis: Results from a randomized placebo controlled trial

BACKGROUND AND AIMS:
Macrophages play a significant role in chronic liver disease as reflected by elevated soluble (s)CD163 and mannose receptor (sMR) levels and associated with liver disease severity and prognosis. Extracellular matrix remodelling associated with fibrogenesis may be affected by sy…

Hepatic System
5. Sep 2018

No effect of rifaximin on soluble CD163, mannose receptor or type III and IV neoepitope collagen markers in decompensated cirrhosis: Results from a randomized, placebo controlled trial.

BACKGROUND AND AIMS:
Macrophages play a significant role in chronic liver disease as reflected by elevated soluble (s)CD163 and mannose receptor (sMR) levels and associated with liver disease severity and prognosis. Extracellular matrix remodelling associated with fibrogenesis may be affected by sy…

Hepatic System, Hepatitis B/C
3. Sep 2018

A STAT4 variant increases liver fibrosis risk in Caucasian patients with chronic hepatitis B.

BACKGROUND:
Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with…

Hepatic System
30. Aug 2018

Assessment of liver fibrosis progresion and regression by a serological collagen turnover profile

OBJECTIVE:
There is a need for non-invasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to anti-fibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be inc…

Hepatitis B/C, Hepatic System
30. Aug 2018

Assessment of Liver Fibrosis Progression and Regression by a Serological Collagen Turnover Profile.

OBJECTIVE:
There is a need for non-invasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to anti-fibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be inc…

Hepatic System
16. Jul 2018

Serological markers of extracellular matrix remodeling predict transplant-free survival in primary sclerosing cholangitis

BACKGROUND:
Primary sclerosing cholangitis is a progressive liver disease with a remarkably variable course. Biomarkers of disease activity or prognostic models predicting outcome at an individual level are currently not established.

AIM:
To evaluate the prognostic utility of four biomarkers of…

Non-Alcoholic Fatty Liver Disease, Hepatic System
16. Jul 2018

ADAPT: An algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis.

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, …

Hepatic System
18. Jan 2018

Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis

Patients with end-stage liver disease develop acute decompensation (AD) episodes, which become more frequent and might develop into acute-on-chronic liver failure (ACLF). However, it remains unknown how AD induces acceleration of liver disease. We hypothesized that remodeling of collagen type III pl…

Hepatic System, Extracellular Matrix Research
6. Nov 2017

Inducible knockdown of procollagen I protects mice from liver fibrosis and leads to dysregulated matrix genes and attenuated inflammation

Organ fibrosis is characterized by a chronic wound-healing response, with excess deposition of extracellular matrix components. Here, collagen type I represents the most abundant scar component and a primary target for antifibrotic therapies. Liver fibrosis can progress to cirrhosis and primary live…

Gastrointestinal, Hepatitis B/C, Hepatic System
25. Oct 2017

PRO-C3: a new and more precise collagen marker for liver fibrosis in patients with chronic hepatitis C

OBJECTIVE:
Detecting significant fibrosis and cirrhosis remains important in treatment and follow-up of patients with chronic hepatitis C Infection (CHC). The aim of this study was to assess the ability of PRO-C3 to identify significant fibrosis (Ishak score ≥3) and cirrhosis (Ishak score ≥5) both …

Hepatic System, Type 2-Diabetes
20. Oct 2016

Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to anti-fibrotic therapy

There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic tria…

Hepatic System, Hepatitis B/C, Extracellular Matrix Research
3. Oct 2016

Fibrosis is not just fibrosis - basement membrane modelling and collagen metabolism differs between hepatitis B- and C-induced injury

BACKGROUND:
While morphological patterns differ, the molecular phenotype of liver fibrosis is considered a stereotypical response to chronic liver injury. However, with different cellular triggers and networks regulating fibrosis, the molecular responses of the injured liver may not be identical.

Hepatitis B/C, Hepatic System
25. Sep 2015

Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients

BACKGROUND AND AIM:
Detection of advanced fibrosis (Metavir F≥3) is important to identify patients with a high urgency of antiviral treatments vs. those whose treatment could be deferred (F≤2). The aim was to assess the diagnostic value of novel serological extracellular matrix protein fragments as…

Hepatic System, Non-Alcoholic Fatty Liver Disease
3. Jul 2015

Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS

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…

Hepatic System, Non-Alcoholic Fatty Liver Disease
15. May 2015

Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

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…

Hepatic System, Alcoholic Liver Disease
1. May 2015

Pro-C5, a marker of true type V collagen formation and fibrillation, correlates with portal hypertension in patients with alcoholic cirrhosis

BACKGROUND AND AIMS:
The hepatic venous pressure gradient (HVPG) is an important but invasive diagnostic and prognostic marker in cirrhotic patients. The aim of the study was to evaluate a novel biochemical plasma marker of true type V collagen formation (Pro-C5) for describing HVPG.

METHODS:
N…

Extracellular Matrix Research, Hepatitis B/C, Hepatic System
1. Feb 2015

Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C

BACKGROUND & AIMS:
Fibrogenesis results in release of certain extracellular matrix protein fragments into the circulation. We evaluated the diagnostic and prognostic performance of two novel serological markers, the precisely cleaved N-terminal propeptide of type III collagen (Pro-C3) and a peptide…

Hepatic System, Hepatitis B/C
29. Sep 2014

PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension

BACKGROUND:
Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM)…

Extracellular Matrix Research, Hepatic System
5. Aug 2014

Review article: the efficacy of biomarkers in chronic fibroproliferative diseases - early diagnosis and prognosis, with liver fibrosis as an exemplar

BACKGROUND:
Nearly 45% of all deaths are associated with chronic fibroproliferative diseases, of which the primary characteristic is altered remodelling of the extracellular matrix. A major difficulty in developing anti-fibrotic therapies is the lack of accurate and established techniques to estima…

Hepatic System, Alcoholic Liver Disease
5. Nov 2013

Novel serological neo-epitope markers of extracellular matrix proteins for the detection of portal hypertension

BACKGROUND:
The hepatic venous pressure gradient (HVPG) is an invasive, but important diagnostic and prognostic marker in cirrhosis with portal hypertension (PHT). During cirrhosis, remodelling of fibrotic tissue by matrix metalloproteinases (MMPs) is a permanent process generating small fragments …

Hepatic System, Alcoholic Liver Disease
30. Jul 2013

Serum markers of the extracellular matrix remodeling reflect antifibrotic therapy in bile-duct ligated rats

BACKGROUND:
Progression of liver fibrosis is characterized by synthesis and degradation of extracellular matrix (ECM). Matrix-metalloproteinases (MMP) cleave collagen fibers at a specific site and thereby generate soluble fragments of ECM (neo-epitopes). The levels of these neo-epitopes might refle…

Hepatic System
24. May 2013

Peptidyl arginine deiminase inhibitor effect on hepatic fibrogenesis in a CCl4 pre-clinical model o2,454f liver fibrosis

Having previously shown that levels of the citrullinated vimentin peptide VICM are raised in liver fibrosis in rats, we aimed to investigate whether inhibition of citrullination as measured by VICM levels could affect fibrogenesis. Methods: Fibrogenesis was evaluated by quantitative histology and ci…

Extracellular Matrix Research, Hepatic System
15. May 2013

Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases

BACKGROUND:
The proteoglycan biglycan (BGN) is involved in collagen fibril assembly and its fragmentation is likely to be associated with collagen turnover during the pathogenesis of diseases which involve dysregulated extracellular matrix remodeling (ECMR), such as rheumatoid arthritis (RA) and li…

Hepatic System, Alcoholic Liver Disease
14. May 2013

Peptidyl arginine deiminase inhibitor effect on hepatic fibrogenesis in a CCl4 pre-clinical model of liver fibrosis

Having previously shown that levels of the citrullinated vimentin peptide VICM are raised in liver fibrosis in rats, we aimed to investigate whether inhibition of citrullination as measured by VICM levels could affect fibrogenesis.

METHODS:
Fibrogenesis was evaluated by quantitative histology an…

Hepatic System, Alcoholic Liver Disease
19. Apr 2013

The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters

AIM:
The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3).

METHODS:
The monoclonal antibody wa…

Hepatic System, Alcoholic Liver Disease
3. Mar 2013

Protein fingerprinting of the extracellular matrix remodelling in a rat model of liver fibrosis--a serological evaluation

BACKGROUND/AIM:
We investigated nine novel biomarkers of extracellular matrix (ECM) remodelling in a rat model of liver fibrosis.

METHODS:
Liver fibrosis was induced in 52 male Wistar rats by inhalation of carbon tetrachloride and the level of hepatic fibrosis was assessed by Sirius red stainin…

Hepatic System, Alcoholic Liver Disease
13. Dec 2012

Phosphodiesterase inhibition mediates matrix metalloproteinase activity and the level of collagen degradation fragments in a liver fibrosis ex vivo rat model

BACKGROUND:
Accumulation of extracellular matrix (ECM) and increased matrix metalloproteinase (MMP) activity are hallmarks of liver fibrosis. The aim of the present study was to develop a model of liver fibrosis combining ex vivo tissue culture of livers from CCl(4) treated animals with an ELISA de…

Hepatic System, Alcoholic Liver Disease
7. Jun 2012

Circulating levels of a collagen type v propeptide fragment in a carbon tetrachloride reversible model of liver fibrosis

AIM:
To measure levels of the collagen V formation marker CO5-1230 during liver fibrosis progression and regression.

METHODS:
Monoclonal antibodies were raised against the sequence TAALGDIMGH located at the start of the C-terminal propeptide between amino acid position 1230' and 1239' (CO5-1230…

Hepatic System, Alcoholic Liver Disease
16. May 2012

Enzyme-linked immunosorbent serum assay specific for the 7S domain of Collagen Type IV (P4NP 7S): A marker related to the extracellular matrix remodeling during liver fibrogenesis

AIM:
The present study describes the ability of a newly developed N-terminal pro-peptides of type IV collagen 7S domain (P4NP 7S) competitive enzyme-linked immunosorbent assay (ELISA) for describing liver fibrosis. The assay applies a monoclonal antibody specific for a PIVNP 7S epitope 100% homolog…

Hepatic System, Alcoholic Liver Disease
5. Apr 2012

Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

AIM:
To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes.

METHODS:
A monoclonal antibody against the sequence RLRSSVPGV-citrullin…

Hepatic System, Extracellular Matrix Research
3. Jan 2012

Molecular serum markers of liver fibrosis

Fibrosis is a hallmark histologic event of chronic liver diseases and is characterized by the excessive accumulation and reorganization of the extracellular matrix (ECM). The gold standard for assessment of fibrosis is liver biopsy. As this procedure has various limitations, including risk of patien…

Hepatic System, Alcoholic Liver Disease
16. Oct 2011

A novel marker for assessment of liver matrix remodeling: an enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)

A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) and c…

Hepatic System, Non-Alcoholic Fatty Liver Disease
16. Aug 2011

Immunological detection of the type V collagen propeptide fragment, PVCP-1230, in connective tissue remodeling associated with liver fibrosis

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…

Hepatic System, Non-Alcoholic Steatohepatitis
9. Aug 2011

Circulating CO3-610, a degradation product of collagen III, closely reflects liver collagen and portal pressure in rats with fibrosis

BACKGROUND:
Hepatic fibrosis is characterized by intense tissue remodeling, mainly driven by matrix metalloproteinases. We previously identified CO3-610, a type III collagen neoepitope generated by matrix metalloproteinase (MMP)-9, and tested its performance as a fibrosis marker in rats with bile-d…

Hepatic System, Non-Alcoholic Fatty Liver Disease
9. Jun 2011

MMP mediated degradation of type VI collagen is highly associated with liver fibrosis--identification and validation of a novel biochemical marker assay

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 fragme…

Hepatic System, Alcoholic Liver Disease
24. Mar 2011

Measurement of CO3-610, a potential liver biomarker derived from matrix metalloproteinase-9 degradation of collagen type III, in a rat model of reversible carbon-tetrachloride-induced fibrosis

BACKGROUND AND AIM:
The current study utilized a carbon tetrachloride (CCl(4))-induced liver fibrosis model to measure levels of the MMP9-mediated collagen type III degradation fragment CO3-610 (site of cleavage: KNGETGPQGP), during disease progression and regression, and to investigate a potential…

Hepatic System, Non-Alcoholic Fatty Liver Disease
30. Oct 2010

Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

BACKGROUND:
During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via …

Hepatic System, Non-Alcoholic Fatty Liver Disease
10. Jul 2010

A novel assay for extracellular matrix remodeling associated with liver fibrosis: An enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen

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 …

Hepatic System, Non-Alcoholic Fatty Liver Disease
1. Apr 2010

Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats

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 pr…