Performance of models to predict hepatocellular carcinoma risk among UK patients with cirrhosis and cured HCV infection

Abstract

Background & Aims: Hepatocellular carcinoma (HCC) prediction models can inform clinical decisions about HCC screening provided their predictions are robust. We conducted an external validation of 6 HCC prediction models for UK patients with cirrhosis and a HCV virological cure. Methods: Patients with cirrhosis and cured HCV were identified from the Scotland HCV clinical database (N = 2,139) and the STratified medicine to Optimise Treatment of Hepatitis C Virus (STOP-HCV) study (N = 606). We calculated patient values for 4 competing non-genetic HCC prediction models, plus 2 genetic models (for the STOP-HCV cohort only). Follow-up began at the date of sustained virological response (SVR) achievement. HCC diagnoses were identified through linkage to nation-wide cancer, hospitalisation, and mortality registries. We compared discrimination and calibration measures between prediction models. Results: Mean follow-up was 3.4–3.9 years, with 118 (Scotland) and 40 (STOP-HCV) incident HCCs observed. The age-male sex-ALBI-platelet count score (aMAP) model showed the best discrimination; for example, the Concordance index (C-index) in the Scottish cohort was 0.77 (95% CI 0.73–0.81). However, for all models, discrimination varied by cohort (being better for the Scottish cohort) and by age (being better for younger patients). In addition, genetic models performed better in patients with HCV genotype 3. The observed 3-year HCC risk was 3.3% (95% CI 2.6–4.2) and 5.1% (3.5–7.0%) in the Scottish and STOP-HCV cohorts, respectively. These were most closely matched by aMAP, in which the mean predicted 3-year risk was 3.6% and 5.0% in the Scottish and STOP-HCV cohorts, respectively. Conclusions: aMAP was the best-performing model in terms of both discrimination and calibration and, therefore, should be used as a benchmark for rival models to surpass. This study underlines the opportunity for ‘real-world’ risk stratification in patients with cirrhosis and cured HCV. However, auxiliary research is needed to help translate an HCC risk prediction into an HCC-screening decision. Lay summary: Patients with cirrhosis and cured HCV are at high risk of developing liver cancer, although the risk varies substantially from one patient to the next. Risk calculator tools can alert clinicians to patients at high risk and thereby influence decision-making. In this study, we tested the performance of 6 risk calculators in more than 2,500 patients with cirrhosis and cured HCV. We show that some risk calculators are considerably better than others. Overall, we found that the ‘aMAP’ calculator worked the best, but more work is needed to convert predictions into clinical decisions.

Keywords

• Prognosis
• Risk prediction
• Primary liver cancer
• External validation
• Genetic risk scores