Published online Jul 28, 2021. doi: 10.3748/wjg.v27.i28.4687
Peer-review started: January 27, 2021
First decision: February 24, 2021
Revised: March 10, 2021
Accepted: July 13, 2021
Article in press: July 13, 2021
Published online: July 28, 2021
Identifying useful biomarkers to diagnose hepatocellular carcinoma (HCC) remains important priority in clinical research. Recently, various tumor markers including protein induced by vitamin K absence or antagonist-II (PIVKA-II), and novel blood parameter, the Lens culinaris agglutinin- reactive fraction of alpha-fetoprotein (AFP-L3), have been introduced and evaluated.
Several studies showed improved HCC diagnostic ability of the combination of AFP, AFP-L3, and PIVKA-II, than either AFP or PIVKA-II. However, because of the small sample size and the specific characteristics of the study population, conflicting results have been reported.
We aimed to investigate and compare the predictive ability of AFP, AFP-L3, and PIVKA-II as well as their combination for HCC diagnosis in this retrospective study with a large number of patients. Further, we developed and validated a new diagnostic model for HCC.
Patients referred from primary clinics to the Korea University Medical Center for newly noted space occupying lesion in liver or elevated serum AFP level between 2015 and 2019 were enrolled. Their serum AFP level, AFP-L3 fraction, and PIVKA-II level were measured in blood samples collected at their first visit.
It was observed that AFP-L3 level exhibited a considerably higher diagnostic accuracy than with AFP level (P < 0.001). In addition, a novel diagnostic model for HCC, ALPs score, derived from the AFP level, AFP-L3 fraction, and PIVKA-II level showed highest area under the receiver operating characteristics curves of 0.878 for HCC diagnosis. It was significantly higher than those of the AFP level, AFP-L3 fraction, and PIVKA-II level (all P < 0.05).
Finally, AFP-L3 level, calculated by multiplying the AFP level with the AFP-L3 fraction had a significantly higher diagnostic ability than the AFP level for HCC diagnosis. The novel diagnostic model, ALPs score was more valuable compared to individual tumor markers for HCC diagnosis.
Further studies including patients with specific liver disease and studies for external validation and cost-effectiveness are required.