The Clinical Utility of Adding Laminin Gamma 2 Monomer to the PAGE‐B Score for Hepatocellular Carcinoma Surveillance in Chronic Hepatitis B

BACKGROUND AND AIMS: A residual risk of hepatocellular carcinoma (HCC) persists despite the use of nucleos(t)ide analogs (NA) in chronic hepatitis B (CHB) patients. We aimed to assess the utility of baseline serum laminin gamma 2 monomer (LG2m) by integrating PAGE-B score to predict HCC. METHODS: NA-treated CHB patients whose baseline serum LG2m, alpha-fetoprotein (AFP) and PAGE-B score were measured. We evaluated the predictive value of LG2m in subgroups stratified by cirrhosis status and PAGE-B score and proposed a HCC surveillance algorithm. RESULTS: HCC developed in 56 of 1016 patients over a follow-up of 3651 person-years (annual incidence: 1.53%). None of the low PAGE-B patients developed HCC over 5 years. LG2m did not significantly stratify risk in high PAGE-B patients. Conversely, LG2m was significantly predictive of HCC in nonhigh PAGE-B patients (5-year incidence: 5.5% vs. 1.0% for high vs. low LG2m, p = 0.004). Integrating LG2m, AFP, and high PAGE-B achieved a sensitivity of 98.2% for HCC detection. Among patients with a nonhigh PAGE-B score, elevated LG2m was associated with a higher risk of HCC (adjusted HR, 4.40; 95% CI, 1.26-15.44), whereas AFP did not significantly stratify HCC risk in a separate analysis. Intermediate PAGE-B patients with high LG2m should receive closer HCC surveillance (annual incidence: 1.4%) as with high PAGE-B patients did (annual incidence: 1.9%). CONCLUSION: Serum LG2m level was predictive of HCC specifically among patients with intermediate PAGE-B score. Integration of LG2m into a PAGE-B-oriented algorithm provides a biomarker-driven tool for individualized surveillance, which is vital for improving early-stage HCC detection.