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Comprehensive Comparative Analysis of Standard Validated, Genetic, and Novel Biomarkers to Enhance Prognostic Risk-stratification in Patients with Hepatitis C Cirrhosis
Clin Transl Gastroenterol. 2022 Feb 9. doi: 10.14309/ctg.0000000000000462.Online ahead of print.
Hamish Innes123, Alex J Walker4, Jennifer Benselin5, Jane I Grove5, Vincent Pedergnana67, Shang-Kuan Lin7, John McLauchlan8, Sharon J Hutchinson13, Eleanor Barnes7, William L Irving5, Indra Neil Guha5, HCV Research UK; & STOP-HCV Consortia; HCV Research UK; & STOP-HCV Consortia
1School of Health and Life Sciences; Glasgow Caledonian University. Glasgow, UK.
2Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
3Public Health Scotland, Glasgow, UK.
4The DataLab, Centre for Evidence Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford, UK.
5NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
6Laboratoire MIVEGEC (UMR CNRS 5290, UR IRD 224, UM), Montpellier, France.
7Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine and the Oxford NIHR Biomedical Research Centre, Oxford University, UK.
8MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
Background: 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 HCV cirrhosis patients from the UK 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 outcome (LRO) for compensated cirrhosis patients, 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 decompensated subgroup and 98 LROs in the compensated subgroup were reported. The discriminative ability of 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 co-morbidity biomarkers. Improvement of performance was greatest when a validated test was combined with comorbidity or collagen biomarker.