Dynamics of type IV collagen 7S fragment on eradication of HCV with direct antiviral agents: Prognostic and metabolomic impacts

<jats:sec id="sec001"> <jats:title>Background</jats:title> <jats:p>Liver fibrosis is one of the cardinal clinical features of chronic hepatitis C (CHC). However, the mechanisms underlying the evolution and reversion of liver fibrosis after hepatitis C virus (HCV) eradication and their relationship with clinical outcomes and metabolic alterations are not fully elucidated. Whether any non-invasive fibrosis marker can predict prognosis is unknown.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods</jats:title> <jats:p>Between October 2014 and September 2019, 418 patients with CHC or compensated cirrhosis with HCV were prospectively recruited in this observational study. 326 patients that were successfully eradicated with interferon-free direct antiviral agents (IFN-free DAAs) were analyzed. Peri-treatment dynamics of serum levels of type IV collagen 7S fragment (4COL7S), a fibrosis marker, and subsequent clinical outcomes, including hepatic decompensation, newly emerged hepatocellular carcinoma (HCC), and all-cause mortality were analyzed.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Results</jats:title> <jats:p>Ten (3.1%) patients died during the observation period. 4COL7S-defined fibrosis progression (n = 97, 29.8%) at SVR was significantly correlated with worse all-cause mortality post-SVR (<jats:italic>P</jats:italic> = 0.0062) but not with the probability of newly emerged HCC (<jats:italic>P</jats:italic> = 0.24). Prognostic tendency was more prominent in patients with advanced fibrosis (<jats:italic>P</jats:italic>< 0.0001). 4COL7S-defined fibrosis progression at SVR and a baseline platelet count less than 10×10<jats:sup>4</jats:sup>/μL were significantly predicted all-cause mortality (<jats:italic>P</jats:italic> = 0.0051). In exploratory analyses, a decreased 4COL7S at the end of treatment was correlated with a matrix-degrading phenotype that showed higher serum metalloproteinase to tissue inhibitors of metalloproteinase-1 ratios and characteristic metabolic fingerprints such as increased butyrate, some medium-chain fatty acids, anabolic amino acids, and decreased uremia toxins.</jats:p> </jats:sec> <jats:sec id="sec004"> <jats:title>Conclusions</jats:title> <jats:p>Peri-treatment dynamics of serum 4COL7S, a non-invasive fibrosis marker, predict prognosis. Non-invasive fibrosis markers may be useful biomarkers for risk stratification post-SVR.</jats:p> </jats:sec>