Comprehensive comparative analysis of standard validated, genetic, and novel biomarkers to enhance prognostic risk-stratification in patients with hepatitis C cirrhosis

Hamish Innes, Alex J. Walker, Jennifer Benselin, Jane Grove, Vincent Pedergnana, M. Azim Ansari, Shang-Kuan Lin, John McLauchlan, Sharon J. Hutchinson, Eleanor Barnes, William L. Irving, Indra Neil Guha, HCV Research UK9, & STOP-HCV10, Consortia

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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.


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.


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).


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.

Original languageEnglish
Article numbere00462
JournalClinical and Translational Gastroenterology
Issue number3
Early online date9 Feb 2022
Publication statusPublished - Mar 2022


  • prognostic risk-stratification
  • patients
  • Hepatitis C
  • cirrhosis
  • prognosis
  • prospective studies
  • hepacivirus/genetics
  • humans
  • liver cirrhosis/diagnosis
  • biomarkers

ASJC Scopus subject areas

  • Gastroenterology


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