Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B

Jung Wha Chung,Hyuk Yoon,Chung Seop Lee,Joon Chang Song,Eun Sun Jang,Cheol Min Shin,Nayoung Kim,Beom Hee Kim,Jaihwan Kim,Jin-Hyeok Hwang,Soyeon Ahn,Hyung Rae Sohn,Jin-Wook Kim,Gi Hyun Kim,Young Soo Park,Bo Young Min,Hyun Kyung Park,Dong Hoon Lee ,Jae-Bong Lee ,Sook‐Hyang Jeong

doi:10.1371/journal.pone.0168189

Jung Wha Chung, Hyuk Yoon + Show 18 more

Open Access

https://doi.org/10.1371/journal.pone.0168189

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Abstract

Although alpha-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance, disease activity may also increase AFP levels in chronic hepatitis B (CHB). Since nucleos(t)ide analog (NA) therapy may reduce not only HBV viral loads and transaminase levels but also the falsely elevated AFP levels in CHB, we tried to determine whether exposure to NA therapy influences AFP performance and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. A retrospective cohort of 6,453 CHB patients who received HCC surveillance was constructed from the electronic clinical data warehouse. Covariates of AFP elevation were determined from 53,137 AFP measurements, and covariate-specific receiver operating characteristics regression analysis revealed that albumin levels and exposure to NA therapy were independent determinants of AFP performance. C statistics were largest in patients with albumin levels ≥ 3.7 g/dL who were followed without NA therapy during study period, whereas AFP performance was poorest when tested in patients with NA therapy during study and albumin levels were < 3.7 g/dL (difference in C statics = 0.35, p < 0.0001). Contrary to expectation, CHB patients with current or recent exposure to NA therapy showed poorer performance of AFP during HCC surveillance. Combination of concomitant albumin levels and status of NA therapy can identify subgroup of CHB patients who will show optimized AFP performance.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men ant the seventh in women worldwide [1]
We performed covariate-specific receiver operating characteristics regression analysis to determine covariates which independently influence the performance of AFP, and compared C statistics of AFP according to the covariates to identify subgroup(s) with optimized AFP performance among chronic hepatitis B (CHB) patients on HCC surveillance
After excluding patients with incomplete surveillance data, HCC diagnosed within 6 months of surveillance or other viral coinfection, 6,453 patients were included in the cohort (Fig 1)

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men ant the seventh in women worldwide [1]. Determinants of AFP elevation have been well defined, it has not been proven whether viral replication and oral NA therapy significantly modify overall test performance of AFP in HBV-associated HCC surveillance. We tried to determine whether NA therapy modifies overall AFP performance, and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. To achieve these goals, we performed covariate-specific receiver operating characteristics regression analysis to determine covariates which independently influence the performance of AFP, and compared C statistics of AFP according to the covariates to identify subgroup(s) with optimized AFP performance among CHB patients on HCC surveillance

Study design and population

Results

Discussion