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HBcrAg-based risk score performs better than the HBV DNA-based scores for HCC prediction in grey zone patients who
Tai-Chung Tseng1,2,3, Tetsuya Hosaka4, Chun-Jen Liu1,2,5
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Insights
A new risk score using HBcrAg predicts hepatocellular carcinoma (HCC) better than HBV DNA scores in HBeAg-negative patients. This score helps manage patients in the grey zone (GZ) by identifying low and high-risk individuals.
Area of Science:
- Hepatology
- Virology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) risk prediction in chronic hepatitis B (CHB) patients is crucial.
- Current risk scores have limitations, especially in HBeAg-negative patients within the grey zone (GZ).
Purpose of the Study:
- To develop and validate a novel HCC risk score based on HBcrAg for HBeAg-negative patients in the GZ.
- To compare the predictive accuracy of the new HBcrAg-based score against existing HBV DNA-based scores.
Main Methods:
- Retrospective derivation and validation cohorts of HBeAg-negative, non-cirrhotic, treatment-naive patients (N=911 Taiwanese, N=806 Japanese).
- Development of a 20-point GZ-HCC score incorporating age, sex, ALT, platelet count, and HBcrAg.
- Evaluation of predictive accuracy using Area Under the Receiver Operating Characteristic Curve (AUROC).
Main Results:
- The HBcrAg-based GZ-HCC score demonstrated superior predictive performance (10-15 year AUROC 0.83-0.86) compared to HBV DNA-based scores (REACH-B, GAG-HCC; AUROC 0.66-0.74).
- The score's efficacy was consistent across different GZ definitions and in the validation cohort.
- Stratification by a score of 8 effectively categorized patients into low-risk (similar to inactive CHB) and high-risk (similar to immune-active CHB) groups.
Conclusions:
- The HBcrAg-based GZ-HCC score is a more accurate predictor of HCC in HBeAg-negative GZ patients than current HBV DNA-based scores.
- This validated risk score can aid in optimizing clinical management, including follow-up and treatment decisions for GZ patients.
Background & Aims:
Risk scores have been designed to predict the development of hepatocellular carcinoma (HCC) in treatment-naive patients with chronic hepatitis B (CHB). However, little is known about their predictive accuracy in HBeAg-negative patients in the grey zone (GZ). We aimed to develop a HBcrAg-based HCC risk score and explore whether it outperforms other risk scores in GZ patients.
Methods:
Two retrospective cohorts of HBeAg-negative patients with American Association for the Study of Liver Diseases-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.
Results:
In a median follow-up period of 15.5 years, 85 patients developed HCC in the derivation cohort. We found that age, sex, alanine aminotransferase, 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 (AUROC) ranged from 0.83 to 0.86, which outperformed the HBV DNA-based HCC risk scores, including REACH-B and GAG-HCC scores (AUROC ranging from 0.66 to 0.74). The better performance was also validated in EASL- and Asian Pacific Association for the Study of the Liver-defined GZ patients. These findings remained consistent in the validation cohort. Finally, the low-risk and high-risk GZ patients (stratified by a score of 8) had an HCC risk close to inactive CHB and immune-active CHB patients, respectively, in both cohorts.
Conclusions:
The HBcrAg-based GZ-HCC score predicts HCC better than other HBV DNA-based risk scores in GZ patients who are HBeAg-negative patients, which may help optimise their clinical management.
Impact And Implications:
We have developed a risk score based on HBcrAg, which has shown better predictive ability for HCC compared with other risk scores based on HBV DNA. Using a score of 8, GZ patients can be classified into low- and high-risk groups, which can guide follow up and early treatment, respectively. This validated risk score is a valuable tool for optimising the management of GZ patients who are HBeAg-negative.
