Screening of Hepatocellular Carcinoma in Hepatic Cirrhosis Patients by a Novel Blood-Based Multi-Omics Test.

IntroductionHepatocellular carcinoma (HCC) screening in patients with hepatic cirrhosis (HC) relies on ultrasound and alpha-fetoprotein (US + AFP), which has limitations in sensitivity, particularly for early-stage HCC detection. This study aims to evaluate the performance of a novel multi-omics blood test, HCCscreen, with its individual components (methylation, AFP, Des-γ-Carboxy Prothrombin (DCP), mutations) and the standard US + AFP for HCC screening in a hepatic cirrhotic population.MethodsA total of 5078 patients with known high-risk for HCC were recruited. A prospective screening study was conducted on 650 patients with hepatic cirrhosis identified by ultrasound. Blood samples were collected from all patients before the confirmation of diagnosis by imaging and/or pathological examinations. The performance of HCCscreen, individual markers and US + AFP were calculated and compared. Statistics was performed with Graphpad Prism 5.0.ResultsHCCscreen exhibited a sensitivity of 86.3% at a specificity of 81.3%, with a positive predictive value (PPV) of 28.2% and a negative predictive value (NPV) of 98.6%. The positive likelihood ratio (LR+) was 4.61 and the negative LR (LR-) was 0.17. The positive detection rate (PDR) for all markers increased with more advanced HCC stages, whether Barcelona Clinic Liver Cancer (BCLC) or clinical staging. Among the single-omics, methylation showed the highest PDR, followed by AFP, DCP and mutations. HCCscreen demonstrated superior overall performance with an AUC of 0.87, outperforming individual markers like methylation (AUC = 0.76), AFP (AUC = 0.83), and DCP (AUC = 0.77). Crucially, HCCscreen's PDR was significantly higher than US + AFP in early-stage HCC (BCLC-0 and clinical stage I). Furthermore, while AFP's PDR varied significantly by sex, HCCscreen's performance remained consistent across all demographics. Correlation analysis revealed a significant association only between the HCCscreen score and the methylation score.ConclusionsThe multi-omics approach of HCCscreen significantly enhances early HCC detection in patients with hepatic cirrhosis compared to both its individual components and the current standard of US + AFP. Its robust and consistent performance across patient demographics underscores its potential as a superior tool for population-wide early HCC screening.