TOPLINE:

Hepatitis B surface antigen (HBsAg) seroclearance did not eliminate the risk for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. A model that incorporated age, sex, cirrhosis status, platelet count, albumin level, and the mode of HBsAg seroclearance showed good performance in predicting the risk for HCC among patients who achieved seroclearance.

METHODOLOGY:

• A reliable HCC prediction model is essential for meeting the 2030 hepatitis elimination targets; however, existing risk scores have been derived from patients with active chronic hepatitis B infection, limiting their applicability to patients who have achieved HBsAg seroclearance.
• Between January 2006 and June 2025, researchers retrospectively assessed 3852 patients with chronic hepatitis B (mean age, 46.4 years; 62.1% men) who achieved HBsAg seroclearance to develop and validate a model for predicting the risk for HCC and to compare its performance with existing models.
• The primary endpoint was the development of HCC; the follow-up duration was measured from the date of HBsAg seroclearance to the date of HCC development (median follow-up duration, 5.64 years).
• The prediction performance of the model was compared with existing prediction models using the area under the curve (AUC) of time-dependent receiver operating characteristic curves at 3, 5, and 10 years.
• HBsAg seroclearance was defined as the loss of detectable HBsAg as noted on two consecutive blood tests performed at least 6 months apart following prior documented HBsAg positivity.

TAKEAWAY:

• Overall, 3.3% of patients developed HCC, with an annual incidence rate of 0.59% (95% CI, 0.49-0.69) and cumulative incidence rates of 2.43%, 3.19%, and 5.40% at 3, 5, and 10 years, respectively.
• Older age (adjusted hazard ratio [aHR], 1.037), male sex (aHR, 1.828), lower platelet count (aHR, 0.997), lower serum albumin level (aHR, 0.971), cirrhosis (aHR, 2.210), and antiviral therapy-induced HBsAg seroclearance (aHR, 2.293; P < .05 for all) were identified as independent predictors of HCC after HBsAg seroclearance.
• The novel model based on these six independent predictors achieved a higher time-dependent AUC than the existing models, including PAGE-B, modified PAGE-B, and CAMP-B, at all evaluated timepoints: 0.79 vs 0.75, 0.76, and 0.73 at 3 years; 0.78 vs 0.75, 0.77, and 0.73 at 5 years; and 0.83 vs 0.78, 0.80, and 0.79 at 10 years, respectively.

IN PRACTICE:

“This model provides a reliable tool for risk stratification, offering a practical framework to personalize HCC surveillance and optimize clinical management for patients who have achieved HBsAg loss,” the authors wrote.

SOURCE:

This study was led by Shuaibing Ying, Zhejiang University School of Medicine, Hangzhou, China. It was published online in Alimentary Pharmacology & Therapeutics.

LIMITATIONS:

The study cohort included only Chinese patients with hepatitis B virus (HBV) genotype C infection from a tertiary referral center, potentially limiting the generalizability of the findings to other populations. The retrospective design could have introduced potential information bias for key confounders, such as family history of HCC, alcohol use, metabolic factors, performance status, and use of preventive medications. Baseline HBV DNA levels were unavailable or undetectable for many patients, limiting the assessment of viral factors.

DISCLOSURES:

This study was supported by national, provincial, and institutional research grants, including the Clinical Collaboration Project on Integrated Traditional Chinese and Western Medicine for Major and Difficult Diseases, the Major Project under the Basic Public Welfare Research Program of Zhejiang Province, and the Developmental Project under the Major Research Plan of the National Natural Science Foundation of China. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.