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J Transl Med. 2016 Jul 4;14(1):201. doi: 10.1186/s12967-016-0952-3.

Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients.

Author information

1
Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801, Bochum, Germany. thilo.bracht@rub.de.
2
Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Bochum, Germany.
3
Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801, Bochum, Germany.
4
Molecular Proteomics Laboratory (MPL), Biologisch-Medizinisches Forschungszentrum (BMFZ), Heinrich-Heine-Universität, Düsseldorf, Germany.
5
Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

Abstract

BACKGROUND:

The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of MFAP4 as biomarker for hepatic fibrosis with a focus on the differentiation of no to moderate (F0-F2) and severe fibrosis stages and cirrhosis (F3 and F4, Desmet-Scheuer scoring system).

METHODS:

MFAP4 levels were measured using an AlphaLISA immunoassay in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without restrictions and considering a lower limit of 80 % sensitivity (correct classification of F3 and F4), respectively. To assess the generalization error, leave-one-out cross validation (LOOCV) was performed.

RESULTS:

MFAP4 levels were shown to differ between no to moderate fibrosis stages F0-F2 and severe stages (F3 and F4) with high statistical significance (t test on log scale, p value <2.2·10(-16)). In the LOOCV, the univariate classification resulted in 85.8 % sensitivity and 54.9 % specificity while the multivariate model yielded 81.3 % sensitivity and 61.5 % specificity (restricted approaches).

CONCLUSIONS:

We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals.

KEYWORDS:

Cirrhosis; Direct acting antivirals; Hepatic fibrosis; Hepatitis C; Microfibrillar-associated protein 4; Serum biomarker

PMID:
27378383
PMCID:
PMC4932744
DOI:
10.1186/s12967-016-0952-3
[Indexed for MEDLINE]
Free PMC Article

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