Improving the Early Detection of Hepatocellular Carcinoma in Patients with Chronic Liver Disease: An Integrated...

Chronic liver disease (CLD) confers an increased risk of hepatocellular carcinoma (HCC), but individual biomarkers have limited diagnostic performance, necessitating a combined approach. The study aimed to evaluate the value of a combined strategy integrating the C-GALAD (gender, age, lens culinaris agglutinin-reactive alpha fetoprotein [AFP-L3], and des-gamma-carboxy prothrombin [DCP]) model with circulating cell-free DNA (cfDNA) for the early detection of progression from CLD to HCC.

A total of 226 patients (HCC, n = 57; CLD without HCC, n = 169) were enrolled. Pretreatment blood samples were collected, and AFP, AFP-L3, and DCP levels were measured; C-GALAD scores were calculated. Plasma cfDNA was extracted and quantified. Baseline clinical characteristics (age, sex, etiology, and cirrhosis) and laboratory parameters (platelet count, total bilirubin, serum albumin [ALB], AFP, AFP-L3, and DCP) were compared between groups. Multivariate logistic regression and receiver operating characteristic curve analysis were performed to identify independent diagnostic factors and evaluated diagnostic performance.

The HCC group had a higher prevalence of cirrhosis, lower ALB levels, and higher AFP, AFP-L3, and DCP levels than the CLD group. Median C-GALAD scores were 51 (interquartile range [IQR], 43-57) in the HCC group and 51 (IQR, 46-58) in the CLD group, whereas cfDNA concentrations were 40.25 (IQR, 33.41-48.19) and 31.62 (25.90-35.45) ng/mL, respectively (both P < .001). Multivariable logistic regression identified cirrhosis (adjusted odds ratio [OR], 3.14; 95% CI, 1.18-8.37; P = .022), C-GALAD score (adjusted OR, 2.32; 95% CI, 1.73-3.10; P < .001), and cfDNA concentration (adjusted OR, 1.20; 95% CI, 1.12 1.30; P < .001) as independent predictors of HCC. The area under the curve (AUC) was 0.850 for C-GALAD (sensitivity, 66.67%; specificity, 89.94%) and 0.799 for cfDNA. The combined model achieved an AUC of 0.917, with a sensitivity of 82.46%, specificity of 91.72%, accuracy of 89.38%, positive predictive value of 77.05%, and negative predictive value of 93.94%.

The combined C-GALAD and cfDNA strategy significantly improves the accuracy of early HCC detection in patients with CLD, demonstrating excellent diagnostic performance.