Prediction of Hepatocellular Carcinoma and Other Liver-Related Events in Chronic Hepatitis B Patients With Metabolic Dysfunction or Metabolic Dysfunction-Associated Steatotic Liver Disease

Introduction: Metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD) are associated with an increased risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to study risk factors for HCC and to assess the performance of the PAGE-B score in this population. Methods: We included CHB patients with ≥ 1 metabolic comorbidity from nine centres. Steatosis was diagnosed by ultrasound, CAP, or histology. Risk factors were analysed by Cox regression, and the performance of the PAGE-B score was assessed in the overall population and across relevant subgroups. Results: We included 1922 patients. 1730 (90.0%) were overweight, 434 (22.6%) had hypertension, 254 (13.2%) dyslipidemia, 230 (12.0%) diabetes and 732 (38.1%) MASLD. Presence of cirrhosis, older age, lower platelets and lower albumin were independent risk factors for HCC. The 5-year HCC risk was 0.1%/2.0%/12.4% patients with low/intermediate/high PAGE-B scores (p < 0.001). Consistent results were obtained in patients with MASLD (0/2.8/11.1% for low, intermediate and high PAGE-B scores (p < 0.001)). PAGE-B stratified risk in patients without cirrhosis (0% vs. 1.2% and 1.8%, p < 0.001). Among the subset of patients with cirrhosis, risks were 4.2% (low), 6.9% (intermediate) and 27.3% (high) (p < 0.001). Conclusions: CHB patients with metabolic dysfunction and/or MASLD are at significant risk of HCC. The PAGE-B score can be used to stratify HCC risk in this population, with negligible 5-year HCC incidence in those without cirrhosis and low PAGE-B scores. However, caution should be exercised in patients with cirrhosis in whom HCC risk remains significant even among those with a low PAGE-B score.