Altered balance between collagen formation and degradation after successful direct-acting antiviral therapy of chronic hepatitis C

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  • Tea Lund Laursen
  • Ida Falk Villesen, Nordic Bioscience AS
  • ,
  • Diana Julie Leeming, Nordic Bioscience AS
  • ,
  • Morten Asser Karsdal, Nordic Bioscience AS
  • ,
  • Christina Sølund, Hvidovre Hospital
  • ,
  • Britta Tarp
  • Lena Hagelskjær Kristensen
  • ,
  • Charlotte Henneberg Holmboe, Aalborg Universitetshospital, Denmark
  • Peter Leutscher, Aalborg University, Regionshospital Nordjylland
  • ,
  • Alex Lund Laursen
  • Natasja Stæhr Gudmann, Nordic Bioscience AS
  • ,
  • Henning Grønbæk

The effect of direct-acting antiviral (DAA) therapy on extracellular matrix (ECM) turnover, a prominent feature of chronic hepatitis C (CHC), is unknown. ECM protein degradation and formation generate fragments reflecting the tissue turnover balance when quantified in the blood. PRO-C3 and PRO-C4 reflect type III and IV collagen formation; C3M and C4M are degradation markers of type III and IV. We aimed to assess the markers’ dynamics with DAA therapy in CHC patients. Plasma PRO-C3, PRO-C4, C3M and C4M were assessed before, during and up till one year after 12-24 weeks of DAA therapy in 77 CHC patients with advanced fibrosis (n = 14) or cirrhosis (n = 63). Liver stiffness was evaluated using transient elastography. PRO-C3, C3M and C4M levels decreased significantly (P <.00001) while PRO-C4 was unchanged (P =.20) during the study period. There was a steep decrease in the PRO-C3/C3M ratio during DAA therapy and follow-up (P <.02). The PRO-C4/C4M ratio was unchanged (P >.27). The dynamics of the collagen markers behaved similarly between patients with advanced fibrosis and cirrhosis. However, the cirrhosis patients had >20% higher levels of C3M, PRO-C4 and C4M at all time points (P <.05). The collagen markers correlated with liver stiffness at baseline and follow-up.Markers of type III and IV collagen formation and degradation decreased during and after successful DAA therapy in CHC patients with advanced liver disease, and associated with disease severity. These results indicate an altered balance between collagen formation and degradation after viral clearance suggesting favourable effects on liver fibrosis.

Original languageEnglish
JournalJournal of Viral Hepatitis
Pages (from-to)236-244
Number of pages9
Publication statusPublished - Feb 2021

    Research areas

  • chronic hepatitis C, collagen markers, direct-acting antiviral therapy, fibrosis, macrophage activation, direct&#8208, MARKER, LIVER FIBROSIS, SUSTAINED VIROLOGICAL RESPONSE, TRANSIENT ELASTOGRAPHY, VENOUS-PRESSURE GRADIENT, CIRRHOSIS, EXTRACELLULAR-MATRIX, PRO-C3, acting antiviral therapy, PORTAL-HYPERTENSION, NONINVASIVE ASSESSMENT

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