Comparative performance of risk prediction models for hepatitis B-related hepatocellular carcinoma in the United States

Abstract

Background & aims: Guidelines recommend hepatocellular carcinoma (HCC) surveillance in patients with chronic HBV infection. Several HCC risk prediction models are available to guide surveillance decisions, but their comparative performance remains unclear.

Methods: Using a retrospective cohort of patients with HBV treated with nucleos(t)ide analogues at 130 Veterans Administration facilities between 9/1/2008 and 12/31/2018, we calculated risk scores from 10 HCC risk prediction models (REACH-B, PAGE-B, m-PAGE-B, CU-HCC, HCC-RESCUE, CAMD, APA-B, REAL-B, AASL-HCC, RWS-HCC). We estimated the models' discrimination and calibration. We calculated HCC incidence in risk categories defined by the reported cut-offs for all models.

Results: Of 3,101 patients with HBV (32.2% with cirrhosis), 47.0% were treated with entecavir, 40.6% tenofovir, and 12.4% received both. During a median follow-up of 4.5 years, 113 patients developed HCC at an incidence of 0.75/100 person-years. AUC values for 3-year HCC risk were the highest for RWS-HCC, APA-B, REAL-B, and AASL-HCC (all >0.80). Of these, 3 (APA-B, RWS-HCC, REAL-B) incorporated alpha-fetoprotein. AUC values for the other models ranged from 0.73 for PAGE-B to 0.79 for CAMD and HCC-RESCUE. Of the 7 models with AUC >0.75, only APA-B was poorly calibrated. In total, 10-20% of the cohort was deemed low-risk based on the published cut-offs. None of the patients in the low-risk groups defined by PAGE-B, m-PAGE-B, AASL-HCC, and REAL-B developed HCC during the study timeframe.

Conclusion: In this national cohort of US-based patients with HBV on antiviral treatment, most models performed well in predicting HCC risk. A low-risk group, in which no cases of HCC occurred within a 3-year timeframe, was identified by several models (PAGE-B, m-PAGE-B, CAMD, AASL-HCC, REAL-B). Further studies are warranted to examine whether these patients could be excluded from HCC surveillance.

Lay summary: Risk prediction models for hepatocellular carcinoma (HCC) in patients infected with hepatitis B virus (HBV) could guide HCC surveillance decisions. In this large cohort of US-based patients receiving treatment for HBV, most published models discriminated between those who did or did not develop HCC, although the RWS-HCC, REAL-B, and AASL-HCC performed the best. If confirmed in future studies, these models could help identify a low-risk subset of patients on antiviral treatment who could be excluded from HCC surveillance.

Keywords: Hepatitis B virus; external validation; hepatocelluar carcinoma.

Fig. 1.. Calibration plot of HBV-HCC prediction models for HCC risk at 3 years.

X axis denotes the scores of HBV-HCC prediction model and Y axis denotes HCC cumulative incidence rate, ranging from 0 to 1. Calibration plots were made to visualize the relationship between predicted risk score and observed HCC risk within the 3-year time window using a logistic regression model. AASL-HCC, age, albumin, sex, liver cirrhosis-HCC; AFP, alpha-fetoprotein; APA-B, age, platelet, AFP; CAMD, cirrhosis, age, male sex, and diabetes mellitus; CU-HCC, Chinese University HCC; HCC, hepatocellular carcinoma; HCC-RESCUE, HCC-Risk Estimating Score in CHB patients Under Entecavir; mPAGE-B, modified PAGE-B; REACH-B, Risk estimation for hepatocellular carcinoma in chronic hepatitis B; REAL-B, Real-World Effectiveness From the Asia Pacific Rim Liver Consortium for HBV Risk Score; RWS-HCC, Real-world risk score for hepatocellular carcinoma.