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Comprehensive Comparative Analysis of Standard Validated, Genetic, and Novel Biomarkers to Enhance Prognostic Risk-Stratification in Patients With Hepatitis C Virus Cirrhosis

Innes, Hamish; Walker, Alex J.; Benselin, Jennifer; Grove, Jane I.; Pedergnana, Vincent; Azim Ansari, M.; Lin, Shang Kuan; McLauchlan, John; Hutchinson, Sharon J.; Barnes, Eleanor; Irving, William L.; Guha, Indra Neil

Comprehensive Comparative Analysis of Standard Validated, Genetic, and Novel Biomarkers to Enhance Prognostic Risk-Stratification in Patients With Hepatitis C Virus Cirrhosis Thumbnail


Authors

Hamish Innes

Alex J. Walker

Jennifer Benselin

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JANE GROVE jane.grove@nottingham.ac.uk
Assistant Professor

Vincent Pedergnana

M. Azim Ansari

Shang Kuan Lin

John McLauchlan

Sharon J. Hutchinson

Eleanor Barnes

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NEIL GUHA neil.guha@nottingham.ac.uk
Professor of Hepatology



Abstract

INTRODUCTION: Risk-stratifying patients with hepatitis C virus (HCV) cirrhosis according to medium-term prognosis will inform clinical decision-making. It is unclear which biomarkers/models are optimal for this purpose. We quantified the discriminative ability of 14 diverse biomarkers for prognosis prediction over a 4-year time. METHODS: We recruited 1196 patients with HCV cirrhosis from the United Kingdom for a prospective study. Genetic risk score, collagen (e.g., PROC3), comorbidity (e.g., CirCom), and validated biomarkers from routine data were measured at enrollment. Participants were linked to UK hospital admission, cancer, and mortality registries. Primary endpoints were (i) liver-related outcomes for patients with compensated cirrhosis and (ii) all-cause mortality for decompensated cirrhosis. The discriminative ability of all biomarkers was quantified individually and also by the fraction of new prognostic information provided. RESULTS: At enrollment, 289 (24%) and 907 (76%) had decompensated and compensated cirrhosis, respectively. Participants were followed for 3-4 years on average, with >70% of the follow-up time occurring post-HCV cure. Seventy-five deaths in the decompensated subgroup and 98 liver-related outcomes in the compensated subgroup were reported. The discriminative ability of the albumin-bilirubin-fibrosis-4 index (C-index: 0.71-0.72) was superior to collagen biomarkers (C-index = 0.58-0.67), genetic risk scores (C-index = 0.50-0.57), and comorbidity markers (0.53-0.60). Validated biomarkers showed the greatest prognostic improvement when combined with a comorbidity or a collagen biomarker (generally >30% of new prognostic information added). DISCUSSION: Inexpensive biomarkers such as the albumin-bilirubin-fibrosis-4 index predict medium-term cirrhosis prognosis moderately well and outperform collagen, genetic, and comorbidity biomarkers. Improvement of performance was greatest when a validated test was combined with comorbidity or collagen biomarker.

Citation

Innes, H., Walker, A. J., Benselin, J., Grove, J. I., Pedergnana, V., Azim Ansari, M., …Guha, I. N. (2022). Comprehensive Comparative Analysis of Standard Validated, Genetic, and Novel Biomarkers to Enhance Prognostic Risk-Stratification in Patients With Hepatitis C Virus Cirrhosis. Clinical and Translational Gastroenterology, 13(3), Article e00462. https://doi.org/10.14309/ctg.0000000000000462

Journal Article Type Article
Acceptance Date Dec 6, 2021
Online Publication Date Feb 9, 2022
Publication Date Feb 9, 2022
Deposit Date Dec 9, 2021
Publicly Available Date Mar 29, 2024
Journal Clinical and Translational Gastroenterology
Electronic ISSN 2155-384X
Publisher Ovid Technologies (Wolters Kluwer Health)
Peer Reviewed Peer Reviewed
Volume 13
Issue 3
Article Number e00462
DOI https://doi.org/10.14309/ctg.0000000000000462
Keywords Gastroenterology
Public URL https://nottingham-repository.worktribe.com/output/6914368
Publisher URL https://journals.lww.com/ctg/Abstract/9900/Comprehensive_Comparative_Analysis_of_Standard.23.aspx

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