A Novel Online Calculator Based on Serum Biomarkers to Detect Hepatocellular Carcinoma among Patients with Hepatitis B

作者：Tian Yang, Hao Xing, Guoqiang Wang, Nianyue Wang, Miaoxia Liu, Cunling Yan, Huijun Li, Lianhua Wei, Shunjun Li, Zhuping Fan, Ming Shi, Wei Chen, Shangli Cai, Timothy M. Pawlik, Andrew Soh, Agim Beshiri, Wan Yee Lau, Mengchao Wu, Yijie Zheng, Feng Shen · 发表于：Clinical Chemistry · 年份：2019 · DOI：10.1373/clinchem.2019.308965 · 被引用次数：120 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Hepatitis B Virus Studies、Liver Disease Diagnosis and Treatment

BACKGROUND: Early detection of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-infected patients remains a challenge, especially in China. We sought to create an online calculator of serum biomarkers to detect HCC among patients with chronic hepatitis B (CHB). METHODS: Participants with HBV-HCC, CHB, HBV-related liver cirrhosis (HBV-LC), benign hepatic tumors, and healthy controls (HCs) were recruited at 11 Chinese hospitals. Potential serum HCC biomarkers, protein induced by vitamin K absence or antagonist-II (PIVKA-II), α-fetoprotein (AFP), lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and α-l-fucosidase (AFU) were evaluated in the pilot cohort. The calculator was built in the training cohort via logistic regression model and validated in the validation cohort. RESULTS: In the pilot study, PIVKA-II and AFP showed better diagnostic sensitivity and specificity compared with AFP-L3 and AFU and were chosen for further study. A combination of PIVKA-II and AFP demonstrated better diagnostic accuracy in differentiating patients with HBV-HCC from patients with CHB or HBV-LC than AFP or PIVKA-II alone [area under the curve (AUC), 0.922 (95% CI, 0.908-0.935), sensitivity 88.3% and specificity 85.1% for the training cohort; 0.902 (95% CI, 0.875-0.929), 87.8%, and 81.0%, respectively, for the validation cohort]. The nomogram including AFP, PIVKA-II, age, and sex performed well in predicting HBV-HCC with good calibration and discrimination [AUC, 0.941 (95% C...