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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.

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Journal article


Clin Transl Gastroenterol

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