Existing models predicting hepatocellular carcinoma (HCC) occurrence do not account for competing risk events, and thus may overestimate the probability of HCC. Our goal was to quantify this bias for patients with cirrhosis and cured hepatitis C.
We analysed a cohort of cirrhosis patients with cured hepatitis C infection from Scotland. Two HCC prognostic models were developed: 1) a Cox regression model ignoring competing risk events; 2) a Fine-Gray regression model accounting for non-HCC mortality as a competing risk. Both models included the same set of prognostic factors used by previously developed HCC prognostic models. Two predictions were calculated for each patient; First, the three-year probability of HCC predicted by model 1; Second, the three-year probability of HCC predicted by model 2.
1629 patients with cirrhosis and cured HCV were followed for 3.8 years on average. A total of 82 incident HCC events and 159 competing risk events (i.e. non-HCC deaths) were observed. The mean predicted 3-year probability of HCC was 3.37% for model 1 (Cox) and 3.24% for model 2 (Fine-Gray). For the majority of patients (76%), the difference in the 3-year probability of HCC predicted by model 1 and model 2 was minimal (i.e. within 0 to ±0.3%). 2.6% of patients had a large discrepancy exceeding 2% - however, these were all patients with a 3-year probability exceeding >5% in both models.
Prognostic models that ignore competing risks do overestimate the future probability of developing HCC. However, the degree of overestimation – and the way it is patterned – means that the impact on HCC screening decisions is likely to be modest.