The aMAP score combined with plasma cfDNA methylation testing for risk stratification in hepatitis population: a case-control study.

Effective surveillance of the hepatitis populations reduces liver cancer incidence and improves prognosis. This study aimed to develop an easy and non-invasive risk assessment model for this population. A total of 392 subjects were included in the present study, comprising 72 cases of chronic hepatitis, 31 cases of liver fibrosis, 152 cases of cirrhosis and 137 cases of liver cancer from diverse ethnic groups in China. Concurrent evaluation of the methylation levels of the GNB4 and Riplet genes in plasma, alongside the age-male-albumin-bilirubin-platelet (aMAP) score and serum AFP, was performed for each subject. Head-to-head comparisons demonstrated that methylation is a superior diagnostic biomarker for liver cancer relative to AFP and aMAP scores. The sensitivity and specificity of GNB4/Riplet methylation for detecting liver cancer were 87.59% (95% confidence interval [CI]: 80.61%-92.40%) and 93.33% (95% CI: 89.25%-95.95%), respectively. For TNM stage I and II liver cancer, methylation showed sensitivities of 69.70% (95% CI: 51.13%-83.79%) and 91.18% (95% CI: 75.19%-97.69%), respectively. The aMAP score yielded an area under the curve (AUC) of 0.745 (95% CI: 0.679–0.812) for differentiating hepatitis from fibrosis/cirrhosis/cancer samples, and an AUC of 0.764 (95% CI: 0.710–0.818) for differentiating hepatitis/fibrosis from cirrhosis/cancer samples. When combining the aMAP score with methylation, the corresponding AUCs increased to 0.825 (95% CI: 0.774–0.875) and 0.867 (95% CI: 0.829–0.905), respectively. The combination of aMAP score and plasma GNB4/Riplet gene methylation shows promise as a tool for risk stratification, which needs external validation in the future.