Competing risk bias in prognostic models predicting hepatocellular carcinoma occurrence: impact on clinical decision making

Hamish Innes*, Philip Johnson, Scott A. McDonald, Victoria Hamill, Alan Yeung, John F. Dillon, Peter C. Hayes, April Went, Stephen T. Barclay, Andrew Fraser, Andrew Bathgate, David J. Goldberg, Sharon J. Hutchinson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

BACKGROUND & AIMS
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.

METHODS
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.

RESULTS
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.

CONCLUSION
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.
Original languageEnglish
Pages (from-to)129–136
Number of pages8
JournalGastro Hep Advances
Volume1
Issue number2
DOIs
Publication statusPublished - 6 Dec 2021

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