Dynamics of type IV collagen 7S fragment on eradication of HCV with direct antiviral agents: Prognostic and metabolomic impacts.
<h4>Background</h4>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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0276925 |
| _version_ | 1798044813637976064 |
|---|---|
| author | Karin Yamataka Po-Sung Chu Yuzo Koda Nobuhito Taniki Rei Morikawa Aya Yoshida Fumie Noguchi Ryosuke Kasuga Takaya Tabuchi Hirotoshi Ebinuma Takanori Kanai Nobuhiro Nakamoto |
| author_facet | Karin Yamataka Po-Sung Chu Yuzo Koda Nobuhito Taniki Rei Morikawa Aya Yoshida Fumie Noguchi Ryosuke Kasuga Takaya Tabuchi Hirotoshi Ebinuma Takanori Kanai Nobuhiro Nakamoto |
| author_sort | Karin Yamataka |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 (P = 0.0062) but not with the probability of newly emerged HCC (P = 0.24). Prognostic tendency was more prominent in patients with advanced fibrosis (P< 0.0001). 4COL7S-defined fibrosis progression at SVR and a baseline platelet count less than 10×104/μL were significantly predicted all-cause mortality (P = 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.<h4>Conclusions</h4>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. |
| first_indexed | 2024-04-11T23:10:20Z |
| format | Article |
| id | doaj.art-eb688791049f48fb9cb42d80b060507b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T23:10:20Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-eb688791049f48fb9cb42d80b060507b2022-12-22T03:57:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011710e027692510.1371/journal.pone.0276925Dynamics of type IV collagen 7S fragment on eradication of HCV with direct antiviral agents: Prognostic and metabolomic impacts.Karin YamatakaPo-Sung ChuYuzo KodaNobuhito TanikiRei MorikawaAya YoshidaFumie NoguchiRyosuke KasugaTakaya TabuchiHirotoshi EbinumaTakanori KanaiNobuhiro Nakamoto<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 (P = 0.0062) but not with the probability of newly emerged HCC (P = 0.24). Prognostic tendency was more prominent in patients with advanced fibrosis (P< 0.0001). 4COL7S-defined fibrosis progression at SVR and a baseline platelet count less than 10×104/μL were significantly predicted all-cause mortality (P = 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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0276925 |
| spellingShingle | Karin Yamataka Po-Sung Chu Yuzo Koda Nobuhito Taniki Rei Morikawa Aya Yoshida Fumie Noguchi Ryosuke Kasuga Takaya Tabuchi Hirotoshi Ebinuma Takanori Kanai Nobuhiro Nakamoto Dynamics of type IV collagen 7S fragment on eradication of HCV with direct antiviral agents: Prognostic and metabolomic impacts. PLoS ONE |
| title | Dynamics of type IV collagen 7S fragment on eradication of HCV with direct antiviral agents: Prognostic and metabolomic impacts. |
| title_full | Dynamics of type IV collagen 7S fragment on eradication of HCV with direct antiviral agents: Prognostic and metabolomic impacts. |
| title_fullStr | Dynamics of type IV collagen 7S fragment on eradication of HCV with direct antiviral agents: Prognostic and metabolomic impacts. |
| title_full_unstemmed | Dynamics of type IV collagen 7S fragment on eradication of HCV with direct antiviral agents: Prognostic and metabolomic impacts. |
| title_short | Dynamics of type IV collagen 7S fragment on eradication of HCV with direct antiviral agents: Prognostic and metabolomic impacts. |
| title_sort | dynamics of type iv collagen 7s fragment on eradication of hcv with direct antiviral agents prognostic and metabolomic impacts |
| url | https://doi.org/10.1371/journal.pone.0276925 |
| work_keys_str_mv | AT karinyamataka dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts AT posungchu dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts AT yuzokoda dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts AT nobuhitotaniki dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts AT reimorikawa dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts AT ayayoshida dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts AT fumienoguchi dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts AT ryosukekasuga dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts AT takayatabuchi dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts AT hirotoshiebinuma dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts AT takanorikanai dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts AT nobuhironakamoto dynamicsoftypeivcollagen7sfragmentoneradicationofhcvwithdirectantiviralagentsprognosticandmetabolomicimpacts |