Direct-acting antivirals-based therapy decreases hepatic fibrosis serum biomarker microfibrillar-associated protein 4 in hepatitis C patients.


Journal

Clinical and molecular hepatology
ISSN: 2287-285X
Titre abrégé: Clin Mol Hepatol
Pays: Korea (South)
ID NLM: 101586730

Informations de publication

Date de publication:
03 2019
Historique:
received: 27 03 2018
accepted: 04 09 2018
pubmed: 20 11 2018
medline: 15 8 2019
entrez: 20 11 2018
Statut: ppublish

Résumé

An estimated 80 million people worldwide are infected with viremic hepatitis C virus (HCV). Even after eradication of HCV with direct acting antivirals (DAAs), hepatic fibrosis remains a risk factor for hepatocarcinogenesis. Recently, we confirmed the applicability of microfibrillar-associated protein 4 (MFAP4) as a serum biomarker for the assessment of hepatic fibrosis. The aim of the present study was to assess the usefulness of MFAP4 as a biomarker of liver fibrosis after HCV eliminating therapy with DAAs. MFAP4 was measured using an immunoassay in 50 hepatitis C patients at baseline (BL), the end-of-therapy (EoT), and the 12-week follow-up visit (FU). Changes in MFAP4 from BL to FU and their association with laboratory parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelets, the AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4), and albumin were analyzed. MFAP4 serum levels were representative of the severity of hepatic fibrosis at BL and correlated well with laboratory parameters, especially APRI (Spearman correlation, R²=0.80). Laboratory parameters decreased significantly from BL to EoT. MFAP4 serum levels were found to decrease from BL and EoT to FU with high statistical significance (Wilcoxon P<0.001 for both). Our findings indicate that viral eradication resulted in reduced MFAP4 serum levels, presumably representing a decrease in hepatic fibrogenesis or fibrosis. Hence, MFAP4 may be a useful tool for risk assessment in hepatitis C patients with advanced fibrosis after eradication of the virus.

Sections du résumé

BACKGROUND/AIMS
An estimated 80 million people worldwide are infected with viremic hepatitis C virus (HCV). Even after eradication of HCV with direct acting antivirals (DAAs), hepatic fibrosis remains a risk factor for hepatocarcinogenesis. Recently, we confirmed the applicability of microfibrillar-associated protein 4 (MFAP4) as a serum biomarker for the assessment of hepatic fibrosis. The aim of the present study was to assess the usefulness of MFAP4 as a biomarker of liver fibrosis after HCV eliminating therapy with DAAs.
METHODS
MFAP4 was measured using an immunoassay in 50 hepatitis C patients at baseline (BL), the end-of-therapy (EoT), and the 12-week follow-up visit (FU). Changes in MFAP4 from BL to FU and their association with laboratory parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelets, the AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4), and albumin were analyzed.
RESULTS
MFAP4 serum levels were representative of the severity of hepatic fibrosis at BL and correlated well with laboratory parameters, especially APRI (Spearman correlation, R²=0.80). Laboratory parameters decreased significantly from BL to EoT. MFAP4 serum levels were found to decrease from BL and EoT to FU with high statistical significance (Wilcoxon P<0.001 for both).
CONCLUSION
Our findings indicate that viral eradication resulted in reduced MFAP4 serum levels, presumably representing a decrease in hepatic fibrogenesis or fibrosis. Hence, MFAP4 may be a useful tool for risk assessment in hepatitis C patients with advanced fibrosis after eradication of the virus.

Identifiants

pubmed: 30449076
pii: cmh.2018.0029
doi: 10.3350/cmh.2018.0029
pmc: PMC6435967
doi:

Substances chimiques

Antiviral Agents 0
Biomarkers 0
Carrier Proteins 0
Extracellular Matrix Proteins 0
Glycoproteins 0
MFAP4 protein, human 0
Aspartate Aminotransferases EC 2.6.1.1
Alanine Transaminase EC 2.6.1.2

Types de publication

Journal Article

Langues

eng

Pagination

42-51

Commentaires et corrections

Type : CommentIn

Références

Ann Intern Med. 2000 Apr 4;132(7):517-24
pubmed: 10744587
J Viral Hepat. 2016 Dec;23(12):994-1002
pubmed: 27500382
Respir Res. 2014 Nov 25;15:147
pubmed: 25425298
Nat Clin Pract Gastroenterol Hepatol. 2007 Nov;4(11):622-34
pubmed: 17978819
J Biol Chem. 2016 Jan 15;291(3):1103-14
pubmed: 26601954
J Hepatol. 1999 May;30(5):783-7
pubmed: 10365802
Histol Histopathol. 2000 Oct;15(4):1159-68
pubmed: 11005241
J Hepatol. 2010 May;52(5):652-7
pubmed: 20346533
J Proteome Res. 2015 May 1;14(5):2278-86
pubmed: 25807371
J Biol Chem. 2000 Jan 28;275(4):2247-50
pubmed: 10644669
Clin Infect Dis. 2015 Jun 15;60(12):1829-36
pubmed: 25761867
Gastroenterology. 2002 May;122(5):1303-13
pubmed: 11984517
Acta Diabetol. 2017 Apr;54(4):367-372
pubmed: 28039584
Gastroenterology. 1999 Nov;117(5):1205-21
pubmed: 10535885
J Hepatol. 2014 Nov;61(1 Suppl):S45-57
pubmed: 25086286
J Viral Hepat. 2008 Mar;15(3):212-8
pubmed: 18179453
Lancet. 2010 Oct 30;376(9751):1441-2
pubmed: 20951421
Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9599-604
pubmed: 11481452
Gastroenterology. 2002 Feb;122(2):352-65
pubmed: 11832450
PLoS One. 2013 Dec 13;8(12):e82243
pubmed: 24349233
Exp Mol Med. 2001 Dec 31;33(4):179-90
pubmed: 11795478
J Transl Med. 2016 Jul 04;14(1):201
pubmed: 27378383
J Viral Hepat. 2014 May;21 Suppl 1:1-4
pubmed: 24713003
Hum Pathol. 2004 Jan;35(1):107-12
pubmed: 14745732
J Hepatol. 2012 Apr;56(4):908-43
pubmed: 22424438
FASEB J. 2002 Feb;16(2):185-94
pubmed: 11818366
World J Gastroenterol. 2016 Jan 28;22(4):1367-81
pubmed: 26819506
Dig Dis Sci. 2003 Jul;48(7):1425-30
pubmed: 12870807
J Hepatol. 1999;31 Suppl 1:17-24
pubmed: 10622555
Ann Intern Med. 2008 Sep 16;149(6):399-403
pubmed: 18794559
Hepatology. 2009 Apr;49(4):1257-66
pubmed: 19177598
Science. 2014 Jul 11;345(6193):141-2
pubmed: 25013048
J Transl Med. 2018 Jun 8;16(1):159
pubmed: 29884190
Hepatology. 2009 Apr;49(4):1335-74
pubmed: 19330875
PLoS One. 2016 Jun 15;11(6):e0155967
pubmed: 27304619
Thorax. 2015 Sep;70(9):862-72
pubmed: 26038533
Clin Infect Dis. 2013 Jul;57(2):230-6
pubmed: 23616492
Arterioscler Thromb Vasc Biol. 2016 Jan;36(1):122-33
pubmed: 26564819
J Gen Virol. 1997 Jul;78 ( Pt 7):1527-31
pubmed: 9225025
Hepatology. 1995 Aug;22(2):426-31
pubmed: 7635409
Front Biosci. 2002 Apr 01;7:d793-807
pubmed: 11897555
Hepatology. 2006 Jun;43(6):1317-25
pubmed: 16729309
PLoS One. 2013 Dec 04;8(12):e82383
pubmed: 24324779
J Hepatol. 1995 Feb;22(2):135-42
pubmed: 7790701
PLoS One. 2015 Oct 13;10(10):e0140418
pubmed: 26460565

Auteurs

Christian Mölleken (C)

Department of Gastroenterology and Hepatology, University Hospital Bergmannsheil, Bochum, Germany.

Maike Ahrens (M)

Medizinisches Proteom-Center, Ruhr University Bochum, Bochum, Germany.
Chrestos Concept GmbH & Co. KG, Essen, Germany.

Anders Schlosser (A)

Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.

Julia Dietz (J)

Medical Clinic 1, J.W. Goethe University Hospital, Frankfurt, Germany.

Martin Eisenacher (M)

Medizinisches Proteom-Center, Ruhr University Bochum, Bochum, Germany.

Helmut E Meyer (HE)

Medizinisches Proteom-Center, Ruhr University Bochum, Bochum, Germany.
Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany.

Wolff Schmiegel (W)

Department of Gastroenterology and Hepatology, University Hospital Bergmannsheil, Bochum, Germany.

Uffe Holmskov (U)

Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.

Christoph Sarrazin (C)

Medical Clinic 1, J.W. Goethe University Hospital, Frankfurt, Germany.
Medical Clinic 2, St. Josefs-Hospital, Wiesbaden, Germany.

Grith Lykke Sorensen (GL)

Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.

Barbara Sitek (B)

Medizinisches Proteom-Center, Ruhr University Bochum, Bochum, Germany.

Thilo Bracht (T)

Medizinisches Proteom-Center, Ruhr University Bochum, Bochum, Germany.

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Classifications MeSH