Systemic inflammation is linked to liver fibrogenesis in patients with advanced chronic liver disease
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Background & Aims: Experimental evidence indicates that systemic inflammation (SI) promotes liver fibrogenesis. This study investigated the potential link between SI and fibrogenesis in patients with advanced chronic liver disease (ACLD). Methods: Serum biomarkers of SI (CRP, IL-6, procalcitonin [PCT]) and extracellular matrix (ECM) turnover (i.e., fibrogenesis/fibrolysis) were analysed in 215 prospectively recruited patients with ACLD (hepatic venous pressure gradient [HVPG] ≥6 mm Hg) undergoing hepatic vein catheterization. Patients with non-elective hospitalization or bacterial infection were excluded. Histological alpha-smooth muscle actin (α-SMA) area was quantified on full biopsy scans by automated morphometric quantification in a subset of 34 patients who underwent concomitant transjugular liver biopsy. Results: Histological α-SMA proportionate area correlated with enhanced liver fibrosis (ELF) score (Spearman's ρ = 0.660, p <.001), markers of collagen formation (PRO-C3, ρ = 0.717, p <.001; PRO-C6, ρ = 0.526, p =.002) and tissue inhibitor of metalloproteinases-1 (TIMP1; ρ = 0.547, p <.001), indicating that these blood biomarkers are capable of reflecting the dynamic process of ECM turnover. CRP, IL-6 and PCT levels correlated with ELF, biomarkers of collagen synthesis/degradation and TIMP1, both in compensated and decompensated patients. Multivariate linear regression models (adjusted for HVPG) confirmed that CRP, IL-6 and PCT were independently linked to markers of liver fibrogenesis and ECM turnover. Conclusion: Systemic inflammation is linked to both liver fibrogenesis and ECM turnover in ACLD and this association is not confounded by the severity of liver disease, as evaluated by HVPG. Our study confirms experimental data on the detrimental impact of SI on ECM deposition and fibrosis progression in a thoroughly characterized cohort of patients with ACLD.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Liver International |
| Vol/bind | 42 |
| Udgave nummer | 11 |
| Sider (fra-til) | 2501-2512 |
| Antal sider | 12 |
| ISSN | 1478-3223 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
BeSi and TR were supported by an International Liver Scholar by Gilead Sciences.
Funding Information:
BeSi has received travel support from AbbVie and Gilead. IFV is a full‐time employee at Nordic Bioscience. PK was co‐supported by the Christian‐Doppler Society and Boehringer Ingelheim, and supported by the Medical Scientific Fund of the Mayor of the City of Vienna (Project: 18070) and awarded to PS. BeSc received travel support from Abbvie and Gilead. DB has received travel support from AbbVie and Gilead, as well as speaker fees from AbbVie. PS received speaking honoraria from Bristol‐Myers Squibb and Boehringer‐Ingelheim, consulting fees from PharmaIN, and travel support from Falk and Phenex Pharmaceuticals. MP is an investigator for Bayer, BMS, Lilly and Roche; he received speaker honoraria from Bayer, BMS, Eisai, Lilly and MSD; he is a consultant for Bayer, BMS, Ipsen, Eisai, Lilly, MSD and Roche; he received travel support from Bayer and BMS. SM received a grant from the NovoNordisk Foundation. MT received grant support from Albireo, Cymabay, Falk, Gilead, Intercept, MSD and Takeda, honoraria for consulting from BiomX, Boehringer Ingelheim, Falk, Genfit, Gilead, Intercept, Janssen, MSD, Novartis, Phenex and Regulus, speaker fees from BMS, Falk, Gilead, Intercept and MSD, as well as travel support from Abbvie, Falk, Gilead and Intercept. MK is a full‐time employee at Nordic Bioscience and among the original inventors and patent holders of the Nordic Bioscience biomarkers. DJL is a full‐time employee at Nordic Bioscience and among the original inventors and patent holders of the Nordic Bioscience biomarkers. TR received grant support from Abbvie, Boehringer‐Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from Abbvie, Bayer, Boehringer‐Ingelheim, Gilead, Intercept, MSD, Siemens and travel support from Abbvie, Boehringer‐Ingelheim, Gilead and Roche. MM served as a speaker and/or consultant and/or advisory board member for AbbVie, Collective Acumen and W. L. Gore & Associates and received travel support from AbbVie and Gilead. RP, AFS, GT, DR, JS and KW declare no conflict of interest.
Publisher Copyright:
© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.
ID: 321286487