||Background & Aims
Risk scores have been designed to predict the development of hepatocellular carcinoma (HCC) in treatment-naïve chronic hepatitis B (CHB) patients. However, little is known about their predictive accuracy in hepatitis B e antigen (HBeAg)-negative patients in grey zone (GZ). We aimed to develop a hepatitis B core-related antigen (HBcrAg)-based HCC risk score and explore whether it outperforms other risk scores in GZ patients.
Two retrospective cohorts of HBeAg-negative patients with AASLD-defined GZ were established for derivation and validation (Taiwanese, N=911; Japanese, N=806). All of them were non-cirrhotic at baseline and remained treatment-naive during the follow-up. The primary endpoint was HCC development.
In a median follow-up period of 15.5 years, 85 patients developed HCC in the derivation cohort. We found that age, sex, ALT, platelet count, and HBcrAg, but not HBV DNA levels, were independent predictors and a 20-point GZ-HCC score was developed accordingly. The 10-year, and 15-year area under the ROC curve (AUC) ranged from 0.83-0.86, which outperformed the HBV DNA-based HCC risk scores, including REACH-B and GAG-HCC scores (AUC ranging from 0.66-0.74). The better performance was also validated in EASL- and APASL-defined GZ patients. These findings remained consistent in the validation cohort. Finally, the low-risk and high-risk GZ patients (stratified by score of 8) had HCC risk close to inactive CHB and immune-active CHB patients, respectively, in both cohorts.
The HBcrAg-based GZ-HCC score predicts HCC better than other HBV DNA-based risk scores in HBeAg-negative GZ patients, which may help optimize their clinical management.