Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 13; pp. 6308 - 6312
• Main Authors: Qu, Chunfeng, Wang, Yuting, Wang, Pei, Chen, Kun, Wang, Minjie, Zeng, Hongmei, Lu, Jianquan, Song, Qianqian, Diplas, Bill H., Tan, Da, Fan, Chunsun, Guo, Qigao, Zhu, Zheng, Yin, Huihui, Jiang, Liping, Chen, Xixi, Zhao, Hui, He, Huan, Wan, Yong, Li, Guangyu, Bi, Xinyu, Zhao, Xinming, Chen, Taoyang, Tang, Hongping, Lv, Chuanguo, Wang, Dongmei, Chen, Wanqing, Zhou, Jianguo, Zhao, Hong, Cai, Jianqiang, Wang, Xiaoyue, Wang, Sizhen, Yan, Hai, Zeng, Yi-Xin, Cavenee, Webster K., Jiao, Yuchen
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 26-03-2019
• Subjects: Assaying; Biological Sciences; Biomarkers, Tumor - blood; Biopsy; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - pathology; Cell-Free Nucleic Acids; Communities; Deoxyribonucleic acid; DNA; Early Detection of Cancer - methods; Hepatitis; Hepatitis B; Hepatitis B surface antigen; Hepatitis B Surface Antigens - blood; Hepatitis B virus; Hepatitis B, Chronic; Hepatocellular carcinoma; Humans; Liquid Biopsy - methods; Liver; Liver cancer; Liver Neoplasms - blood; Liver Neoplasms - diagnosis; Liver Neoplasms - pathology; Nodules; Proteins; Sensitivity; Sensitivity and Specificity; Ultrasonography; Ultrasound; Viruses; HBsAg-seropositive; early detection of cancer; cell free DNA; hepatocellular carcinoma
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1819799116

Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6–8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same time-scale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.