Validation of Hepatocellular Carcinoma Risk Prediction Models in Patients with Hepatitis B-Related Cirrhosis

PURPOSE: Several risk models have been developed to predict the hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B (CHB); however, it remains unclear whether these models are useful for risk assessment in patients with hepatitis B virus (HBV)-related cirrhosis undergoing antiviral therapy. PATIENTS AND METHODS: A total of 252 treatment-naive cirrhosis patients with no history of HCC who underwent treatment with nucleos(t)ide analogues between January 2010 and July 2014 were enrolled. Cox proportional hazards model was used to analyze the risk factors for HCC. “TimeROC” and “survival ROC” package, written for R, were used to compare the time-dependent area under the receiver operating characteristic (AUROC) curves for the predictability of the HCC risk scores. RESULTS: During the mean follow-up period of 56.96 months, 48 (19.0%) patients developed HCC. Cox multivariate stepwise regression analysis revealed that international normalized ratio (hazard ratio [HR] 2.771, 95% confidence interval [CI] 1.462–5.254; P=0.002), alpha-fetoprotein (HR 1.001, 95% CI 1.000–1.003; P=0.035), diabetes mellitus (HR 3.061, 95% CI 1.542–6.077; P=0.001), and alcohol intake (HR 2.250, 95% CI 1.042–4.856; P=0.039) were independent indicators of the HCC risk. AUROC at 3 (0.739) and 5 years (0.695) for the REAL-B score were consistently higher than those of the other risk models except RWS-HCC. The time-dependent AUROC value at 1 year for the REAL-B score was similar to those of the other risk models. According to REAL-B score stratification (0–3, low; 4–7, moderate; and 8–13, high), the HCC risk rates at 1, 3, and 5 years were 2.4%, 5.6%, and 9.0% in the intermediate-risk group, and 7.2%, 21.1%, and 26.3% in the high-risk group, respectively (all P<0.001 between each pair). CONCLUSION: REAL-B score showed a persistently high prognostic capability in predicting the HCC risk in HBV-related cirrhosis patients undergoing antiviral therapy.