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

Clin Mol Hepatol. 2019 Mar;25(1):42-51. doi: 10.3350/cmh.2018.0029. Epub 2018 Nov 19.


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.

Keywords: Antiviral agents; Biomarkers; Extracellular matrix proteins; Hepatitis C, Chronic; Liver cirrhosis.

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood*
  • Carrier Proteins / blood*
  • Extracellular Matrix Proteins / blood*
  • Female
  • Follow-Up Studies
  • Glycoproteins / blood*
  • Hepatitis C / drug therapy*
  • Hepatitis C / pathology
  • Humans
  • Immunoassay
  • Liver / pathology
  • Liver Cirrhosis / pathology*
  • Male
  • Middle Aged
  • Platelet Count
  • Severity of Illness Index
  • Young Adult


  • Antiviral Agents
  • Biomarkers
  • Carrier Proteins
  • Extracellular Matrix Proteins
  • Glycoproteins
  • MFAP4 protein, human
  • Aspartate Aminotransferases
  • Alanine Transaminase