Prospective study of circulating methylated SEPT9 for detection of hepatocellular carcinoma in cirrhosis patients

Hepatocellular carcinoma (HCC) surveillance among patients with cirrhosis remains suboptimal, with inadequate early-stage detection. Α-Fetoprotein (AFP) demonstrates insufficient sensitivity. Circulating methylated septin 9 (SEPT9) has shown diagnostic promise. A prospective study at two academic centers in France investigated whether methylated SEPT9 improves detection of HCC when combined with AFP in patients with cirrhosis undergoing surveillance from February 2018 through October 2024. In this diagnostic study including 574 patients with cirrhosis, the combination of at least single-positive methylated SEPT9 and AFP greater than 20 ng/ml achieved 87.8% sensitivity compared with 44.3% for AFP alone, a significant difference, and recovered 78% of cancers missed by AFP, with an improvement in early-stage sensitivity. The authors conclude that findings from this study indicate that a blood-based combination of epigenomic and protein biomarkers may substantially improve HCC detection during surveillance, particularly for early-stage disease amenable to curative treatment.