A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis.
Journal
Med (New York, N.Y.)
ISSN: 2666-6340
Titre abrégé: Med
Pays: United States
ID NLM: 101769215
Informations de publication
Date de publication:
09 07 2021
09 07 2021
Historique:
entrez:
28
7
2021
pubmed:
29
7
2021
medline:
29
7
2021
Statut:
ppublish
Résumé
Accurate non-invasive prediction of long-term hepatocellular carcinoma (HCC) risk in advanced liver fibrosis is urgently needed for cost-effective HCC screening; however, this currently remains an unmet need. A serum-protein-based prognostic liver secretome signature (PLSec) was bioinformatically derived from previously validated hepatic transcriptome signatures and optimized in 79 patients with advanced liver fibrosis. We independently validated PLSec for HCC risk in 331 cirrhosis patients with mixed etiologies (validation set 1 [V1]) and thereafter developed a score with clinical prognostic variables. The score was then validated in two independent cohorts: validation set 2 (V2): 164 patients with advanced liver fibrosis due to hepatitis C virus (HCV) infection cured after direct-acting antiviral therapy; validation set 3 (V3): 146 patients with advanced liver fibrosis with successfully-treated HCC and cured HCV infection. An 8-protein blood-based PLSec recapitulated transcriptome-based hepatic HCC risk status. In V1, PLSec was significantly associated with incident HCC risk (adjusted hazard ratio [aHR], 2.35; 95% confidence interval [CI], 1.30-4.23). A composite score with serum alpha-fetoprotein (PLSec-AFP) was defined in V1, and validated in V2 (adjusted odds ratio, 3.80 [95%CI, 1.66-8.66]) and V3 (aHR, 3.08 [95%CI, 1.78-5.31]; c-index, 0.74). PLSec-AFP outperformed AFP alone (Brier score, 0.165 vs. 0.186 in V2; 0.196 vs. 0.206 in V3, respectively). The blood-based PLSec-AFP can accurately stratify patients with advanced liver fibrosis for long-term HCC risk and thereby guide risk-based tailored HCC screening.
Sections du résumé
BACKGROUND
Accurate non-invasive prediction of long-term hepatocellular carcinoma (HCC) risk in advanced liver fibrosis is urgently needed for cost-effective HCC screening; however, this currently remains an unmet need.
METHODS
A serum-protein-based prognostic liver secretome signature (PLSec) was bioinformatically derived from previously validated hepatic transcriptome signatures and optimized in 79 patients with advanced liver fibrosis. We independently validated PLSec for HCC risk in 331 cirrhosis patients with mixed etiologies (validation set 1 [V1]) and thereafter developed a score with clinical prognostic variables. The score was then validated in two independent cohorts: validation set 2 (V2): 164 patients with advanced liver fibrosis due to hepatitis C virus (HCV) infection cured after direct-acting antiviral therapy; validation set 3 (V3): 146 patients with advanced liver fibrosis with successfully-treated HCC and cured HCV infection.
FINDINGS
An 8-protein blood-based PLSec recapitulated transcriptome-based hepatic HCC risk status. In V1, PLSec was significantly associated with incident HCC risk (adjusted hazard ratio [aHR], 2.35; 95% confidence interval [CI], 1.30-4.23). A composite score with serum alpha-fetoprotein (PLSec-AFP) was defined in V1, and validated in V2 (adjusted odds ratio, 3.80 [95%CI, 1.66-8.66]) and V3 (aHR, 3.08 [95%CI, 1.78-5.31]; c-index, 0.74). PLSec-AFP outperformed AFP alone (Brier score, 0.165 vs. 0.186 in V2; 0.196 vs. 0.206 in V3, respectively).
CONCLUSIONS
The blood-based PLSec-AFP can accurately stratify patients with advanced liver fibrosis for long-term HCC risk and thereby guide risk-based tailored HCC screening.
Identifiants
pubmed: 34318286
doi: 10.1016/j.medj.2021.03.017
pmc: PMC8312635
mid: NIHMS1690970
doi:
Substances chimiques
Antiviral Agents
0
alpha-Fetoproteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
836-850.e10Subventions
Organisme : NCI NIH HHS
ID : U01 CA226052
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA222900
Pays : United States
Organisme : European Research Council
ID : 671231
Pays : International
Organisme : NCI NIH HHS
ID : U01 CA230694
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK099558
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA237659
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA230669
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA233794
Pays : United States
Commentaires et corrections
Type : CommentIn
Déclaration de conflit d'intérêts
DECLARATION OF INTERESTS Y.H. serves as an advisory board member for Helio Health and founding shareholder for Alentis Therapeutics, and received a research funding from Morphic Therapeutics. T.F.B. serves as advisor and is a founding shareholder or Alentis Therapeutics. R.T received a lecture fee from Bayer, Chugai, Eisai, Takeda and Wako/Fujifilm. N.P. has served as a consultant for Bristol Myers-Squibb, Exact Sciences, Eli Lilly, and Freenome. A.G.S. has served on advisory boards of Genentech, Eisai, Bayer, Exelixis, Wako/Fujifilm and has received research funding from Bayer, Target Pharmasolutions, Exact Sciences, and Glycotest.
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