Abstract
<h3>Background and Aims</h3> 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. <h3>Methods</h3> We analyzed a nationwide cohort of patients with cirrhosis and cured hepatitis C infection from Scotland. Two HCC prognostic models were developed: (1) a Cox regression model ignoring competing risk events and (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 3-year probability of HCC predicted by model 1 and second, the 3-year probability of HCC predicted by model 2. <h3>Results</h3> The study population comprised 1629 patients with cirrhosis and cured HCV, followed for 3.8 years on average. A total of 82 incident HCC events and 159 competing risk events (ie, 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 most patients (76%), the difference in the 3-year probability of HCC predicted by model 1 and model 2 was minimal (ie, within 0 to ±0.3%). A total of 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. <h3>Conclusion</h3> 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.
Highlights
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, responsible for w800,000 deaths every year.[1]
Even though a patient may have a high risk of HCC incidence, if Abbreviations used in this paper: CHD, coronary heart disease; CI, confidence interval; GGT, gamma glutamyl transferase; HCC, hepatocellular carcinoma
Our aim was to select prognostic factors that are being used in existing prediction models for HCC occurrence in a surveillance context
Summary
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, responsible for w800,000 deaths every year.[1]. The number of models predicting a patient’s risk of HCC occurrence in a surveillance context has increased dramatically over the last 5 years.[9,10,11,12,13,14,15,16] such models all share one potentially serious limitation: namely, the failure to take the competing risk event of nonHCC mortality into account This is potentially a serious limitation because typically, patients with cirrhosis do not just face a high risk of HCC, but a high risk of dying from non-HCC–related causes too. The degree of overestimation—and the way it is patterned—means that the impact on HCC screening decisions is likely to be modest
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