Abstract:
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 of degraded extracellular matrix (ECM) proteins known as neoepitopes, which are then released into the circulation. AIM:To investigate their potential as plasma markers for detection of PHT. METHODS:Ninety-four patients with alcoholic cirrhosis and 20 liver-healthy controls were included. Clinical and laboratory data of the patients were collected. All patients received HVPG measurement with blood sampling. In these samples, the following degradation or formation markers were measured: C1M (type I-collagen), C3M and PRO-C3 (type III collagen), C4M and P4NP 7S (type IV collagen), C5M (type V collagen), C6M (type VI collagen), BGM (biglycan), ELM (elastin), CRPM (CRP). RESULTS:All ECM markers except for CRPM correlated significantly with HVPG. Interestingly, C4M, C5M and ELM levels were significantly higher in patients with HVPG >10 mmHg. Multiple regression analysis identified PRO-C3, C6M and ELM as significant determinants, while the models A and B including PRO-C3, ELM, C6M and model for end-stage liver disease (MELD) provided better description of PHT (r = 0.75, P < 0.0001). The models provided odds ratios of >100 for having clinical significant PHT. CONCLUSIONS:These novel non-invasive extracellular matrix markers reflect the degree of liver dysfunction. The different degrees of portal hypertension correlated with these circulating neoepitopes. Using a single blood sample, these neoepitopes in combination with MELD detect the level of portal hypertension.
journal_name
Aliment Pharmacol Therjournal_title
Alimentary pharmacology & therapeuticsauthors
Leeming DJ,Karsdal MA,Byrjalsen I,Bendtsen F,Trebicka J,Nielsen MJ,Christiansen C,Møller S,Krag Adoi
10.1111/apt.12484subject
Has Abstractpub_date
2013-11-01 00:00:00pages
1086-96issue
9eissn
0269-2813issn
1365-2036journal_volume
38pub_type
杂志文章abstract:BACKGROUND:Chronic hepatitis C (HCV) treatment with pegylated-interferon (PEG-IFN)/ribavirin (RBV) is often limited by preexisting medical, psychiatric and psychosocial contraindications. However, limited data exist in general patient populations. AIM:To evaluate the percentage of HCV-infected patients in the general ...
journal_title:Alimentary pharmacology & therapeutics
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