Microfibrillar-Associated Protein 4: A Potential Biomarker for Screening for Liver Fibrosis in a Mixed Patient Cohort

PLoS One. 2015 Oct 13;10(10):e0140418. doi: 10.1371/journal.pone.0140418. eCollection 2015.

Abstract

Background and aims: A method for assessment of liver fibrosis and cirrhosis without the need for a liver biopsy is desirable. Microfibrillar-associated protein 4 (MFAP4) is a suggested biomarker for identification of high-risk patients with severe fibrosis stages. This study aimed to examine associations between plasma MFAP4 (pMFAP4) and transient elastography or chronic hepatitis C virus infection in drug users and in a mixed patient cohort with increased risk of liver disease. Moreover, the study aimed to identify comorbidities that significantly influence pMFAP4.

Methods: pMFAP4 was measured in samples from 351 drug users attending treatment centres and from 248 acutely hospitalized medical patients with mixed diagnoses. Linear and logistic multivariate regression analyses were performed and nonparametric receiver operating characteristic-curves for cirrhosis were used to estimate cut-off points for pMFAP4. Univariate and subgroup analyses were performed using non-parametric methods.

Results: pMFAP4 increased significantly with liver fibrosis score. pMFAP4 was significantly associated with chronic viral infection in the drug users and with transient elastography in both cohorts. In the mixed patient cohort, pMFAP4 was significantly increased among patients with a previous diagnosis of liver disease or congestive heart failure compared to patients with other diagnoses.

Conclusions: pMFAP4 has the potential to be used as an outreach-screening tool for liver fibrosis in drug users and in mixed medical patients. pMFAP4 level is positively associated with transient elastography, but additional studies are warranted to validate the possible use of pMFAP4 in larger cohorts and in combination with transient elastography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Biopsy
  • Carrier Proteins / blood*
  • Cohort Studies
  • Comorbidity
  • Drug Users
  • Elasticity Imaging Techniques
  • Extracellular Matrix Proteins / blood*
  • Female
  • Glycoproteins / blood*
  • Heart Failure / complications
  • Hepatitis C, Chronic / complications
  • Humans
  • Liver / pathology
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Biomarkers
  • Carrier Proteins
  • Extracellular Matrix Proteins
  • Glycoproteins
  • MFAP4 protein, human

Grants and funding

This work was supported by grants from the Region of Southern Denmark PhD-resources (SGS, http://regionsyddanmark.dk/wm325002), Fonden til Læge-videnskabens Fremme (SGS, http://www.apmollerfonde.dk/ansoegning/laegefonden.aspx), Overlægerådet at Odense University Hospital (SGS), and The Free Research Funds from Odense University Research Pool (SGS). The funders had no role in study design, data collection and analysis, decision to publish, or prepara-tion of the manuscript.