Almost one third of carriers of hepatitis B virus (HBV) world-wide are in China and more than 80% hepatocellular carcinoma (HCC) in China are associated with HBV infection. So early detection of HCC in HBV-infected patients is necessary. In the present study, we aimed to develop a diagnostic model by combining protein induced by Vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (AFP) for HBV-related HCC.
We recruited consecutive patients with HBV-related HCC, chronic hepatitis B, HBV-related cirrhosis and healthy controls at 11 hospitals in China from June 2016 to May 2017 for a training cohort. A validation cohort was enrolled at the same sites from FebruaryJune 2017 to September 2017. HCC was defined on the basis of ultrasound, CT, or MRI characteristics and confirmed by histopathology. Serum PIVKA-II level was measured by ARCHITECT immunoassay and AFP was measured with commercially available ELISA. Receiver operating characteristics (ROC) were used to calculate diagnostic accuracy.
The training cohort consisted of 2019 participants, 908 with HBV-related HCC, 289 with chronic hepatitis B, 314 with HBV-related cirrhosis, and 508 healthy controls. The validation cohort comprised 655 participants, 289 with HBV-related HCC, 113 with chronic hepatitis B, 98 with HBV-related cirrhosis, and 155 healthy controls. Levels of PIVKA-II in serum were significantly higher in HBV-related HCC than all controls. ROC curves showed the optimum diagnostic cutoff for PIVKA-II was 44.18 mAU/mL (area under curve [AUC], 0.907 [95% CI 0.892-0.922], sensitivity 81.13%, and specificity 94.97% in the training cohort; 0.909 [0.883-0.934], 79.02%, and 95.46% in the validation cohort). PIVKA-II maintained diagnostic accuracy for patients with HBV-related HCC who were AFP negative. A model combined PIVKA-II, AFP, age, gender and liver cirrhosis improved diagnostic accuracy for HBV-related HCC versus all controls compared with either test alone (0.951 [0.929-0.973] in the training cohort; 0.954 [0.945-0.962] in the validation cohort).
PIVKA-II could complement measurement of AFP in the diagnostic of HBV-related HCC and distinguish HCC from non-malignant chronic liver disease.
Clinical trial identification
Legal entity responsible for the study
Eastern Hepatobiliary Surgery Hospital, Second Military Medical University.
The National Natural Science Foundation of China.
All authors have declared no conflicts of interest.