Refining surveillance of hepatocellular carcinoma in chronic hepatitis B through biomarker-based risk stratification

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with chronic hepatitis B (CHB) accounting for more than half of the cases. Regular surveillance, including abdominal ultrasonography with alpha-fetoprotein testing every 6 months, enables early tumor detection and curative treatment; however, current guideline recommendations based mainly on age, sex, and race/ethnicity insufficiently capture individual risk variation, particularly among patients with CHB who do not have cirrhosis. In addition, real-world adherence to HCC surveillance is suboptimal-fewer than 40% of eligible patients receive surveillance at the recommended 6-month intervals. To improve both efficiency and impact, surveillance resources should be reallocated to patients whose estimated risk exceeds the cost-effective surveillance threshold. Recent studies support biomarker-based risk stratification as a more precise approach. For example, in untreated CHB, HBeAg-negative patients meeting inactive disease criteria with HBsAg <100 IU/mL have an annual HCC incidence below the 0.2% cost-effectiveness threshold, suggesting that routine surveillance may be unnecessary. In antiviral-treated CHB, models such as PAGE-B and its derivatives can accurately identify low-risk patients who may safely forgo HCC surveillance. Conversely, for patients at extremely high risk, including those with cirrhosis, intensified strategies-such as abbreviated MRI or combined biomarker algorithms-may enhance early detection. Collectively, these findings support a transition from a categorical, one-size-fits-all approach toward a precision surveillance paradigm that tailors the need for and intensity of HCC surveillance to biomarker-defined risk, thereby optimizing resource use, improving adherence, and maximizing clinical benefit. Nevertheless, further large-scale, prospective studies across diverse populations are needed to validate biomarker thresholds and confirm the long-term safety of exempting very-low-risk patients with CHB from HCC surveillance.