New Thresholds for AFP and Des-γ-Carboxy Prothrombin in Chronic Liver Disease Depending on the Use of Nucleoside Analogs and an Integrated Nomogram

Abstract

Background The thresholds of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (PIVKA-II) when detecting hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with antiviral nucleoside analog (NA) remain controversial. A relevant integrated nomogram needs to be developed. Methods We enrolled a consecutive series of 5666 cases diagnosed with CHB either with or without antiviral agents and randomly allocated them to the training set (n=3966, 70.00%) and the validation set (n=1700, 30.00%). Results In the training set, the levels of AFP and PIVKA-II of NA-treated patients were significantly lower than those of untreated patients. The most appropriate cut-off values of AFP and PIVKA-II were 151.40 ng/mL (a sensitivity of 39.77% and a specificity of 92.17%) and 35.50 mAU/mL (a sensitivity of 84.85% and a specificity of 69.43%) for NA-treated patients. As for BCLC-0/A HCC, the most appropriate cut-off values of AFP and PIVKA-II were 151.40 ng/mL and 32.50 mAU/mL for NA-treated patients, respectively. A logistic regression model composed of AFP, PIVKA-II and other clinical parameters to predict the risk of HBV-related HCC for NA-treated patients was established and verified to have an AUROC of 0.868 (95% CI, 0.827–0.909) for all-stage HCC and an AUROC of 0.856 (95% CI, 0.809–0.903) for BCLC-0/A HCC. Conclusion The new detection thresholds of AFP and PIVKA-II might lead to the ability to perform early detection for hepatoma in NA-treated patients and the innovative risk prediction model is a valuable tool for identifying high-risk CHB patients.

PIVKA-II or AFP has better diagnostic properties for hepatocellular carcinoma diagnosis in high-risk patients

“…Even though both AFP and PIVKA-II are useful diagnostic markers for HCC, a previous report found that they may not be a good marker for small HCC nodules less than 2 cm as they have sensitivity of approximately 50% (29). However, they may be used for HCC detection particularly in hepatitis virus-related HCC (22,30). A study from China found similar findings as this study but different cutoff for both AFP and PIVKA-II (31).…”

“…These causes related to HCC deaths in 33%, 30%, and 21%, respectively (1). High-risk patients for HCC were patients with cirrhosis, chronic HBV diagnostic method particularly for HCC including AFP and PIVKA-II (20)(21)(22). The advantage of AFP is widely available, while PIVKA-II is highly specific to HCC.…”