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

ABSTRACT: BACKGROUND Hepatocellular carcinoma (HCC) prediction models can inform clinical decisions about HCC screening provided their predictions are robust. We conducted an external validation of six HCC prediction models for UK patients with cirrhosis and a hepatitis C virus (HCV) virological cure. METHODS Cirrhosis patients with cured HCV were identified from the Scotland HCV clinical database (N=2139) and the STOPHCV study (N=606). We calculated patient values for four competing non-genetic HCC prediction models, plus two genetic models (for STOPHCV cohort only). Follow-up began at the date of 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 (STOPHCV) incident HCCs observed. The aMAP (Age-Male gender-Albi score-Platelet count) model showed the best discrimination; e.g. C-index in Scottish cohort was 0.77 (95%CI:0.73-0.81). However, for all models, discrimination varied by cohort (better for Scottish cohort) and by age (better for younger patients). Also, genetic models performed better in HCV genotype 3 patients. 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 STOPHCV cohort respectively. These were most closely matched by aMAP, where the mean predicted 3-year risk was 3.6% and 5.0% in the Scottish and STOPHCV cohorts, respectively. CONCLUSIONS AMAP was the best performing model in terms of both discrimination and calibration and should be used as a benchmark for rival models to surpass. This study underlines the opportunity for “real world” risk stratification in cirrhosis patients with cured HCV. However, auxiliary research is needed to help translate a HCC risk prediction into a HCC screening decision. LAY SUMMARY Patients with cirrhosis and cured hepatitis C are at high risk of liver cancer- but the risk varies substantially from one patient to the next. Risk calculator tools can alert clinicians to high risk patients and thereby influence decision-making. In this study we tested the performance of 6 risk calculators in more than 2500 patients with cirrhosis and cured hepatitis C. 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.