Prediction of liver fibrosis severity in alcoholic liver disease by human microfibrillar-associated protein 4

Bjørn Staehr Madsen*, Maja Thiele, Sönke Detlefsen, Mia Dahl Sørensen, Maria Kjaergaard, Linda Sevelsted Møller, Ditlev Nytoft Rasmussen, Anders Schlosser, Uffe Holmskov, Jonel Trebicka, Grith Lykke Sorensen, Aleksander Krag, Galaxy Consortium

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Background: Alcoholic liver disease (ALD) is a public health concern that is the cause of half of all cirrhosis-related deaths. Early detection of fibrosis, ideally in the precirrhotic stage, is a key strategy for improving ALD outcomes and for preventing progression to cirrhosis. Previous studies identified the blood-borne marker human microfibrillar-associated protein 4 (MFAP4) as a biomarker for detection of hepatitis C virus (HCV)-related fibrosis. Aim: To evaluate the diagnostic accuracy of MFAP4 to detect ALD-induced fibrosis. Method: We performed a prospective, liver biopsy-controlled study involving 266 patients with prior or current alcohol overuse. Patients were split into a training and a validation cohort. Results: MFAP4 was present in fibrotic hepatic tissue and serum MFAP4 levels increased with fibrosis grade. The area under the receiver operating characteristic curve (AUROC) for detection of cirrhosis was 0.91 (95% CI 0.85-0.96) in the training cohort and 0.91 (95% CI 0.79-1.00) in the validation cohort. For detection of advanced fibrosis, the AUROC was 0.88 (95% CI 0.81-0.94) in the training cohort and 0.92 (95% CI 0.83-1.00) in the validation cohort. The diagnostic accuracy did not differ between MFAP4 and the enhanced liver fibrosis (ELF) test or transient elastography (TE) in an intention-to-diagnose analysis. MFAP4 did not predict hepatic decompensation in a time-to-decompensation analysis in a subgroup of patients with cirrhosis. Conclusion: MFAP4 is a novel biomarker that can detect ALD-related fibrosis with high accuracy.

Original languageEnglish
JournalLiver International
Volume40
Issue number7
Pages (from-to)1701-1712
ISSN1478-3223
DOIs
Publication statusPublished - Jul 2020

Keywords

  • biomarker
  • cirrhosis
  • extracellular matrix protein
  • liver biopsy
  • non-invasive testing

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