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

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.

A Large‐Scale Multicenter Study Validates Aldo‐Keto Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of Hepatocellular Carcinoma

“…This may also imply a potential use of AKR1B10 for evaluation of tumor burden, metastasis, and/or recurrence of HCC. Like literature reports, AFP increased in patients with HCC recruited in this study, but AKR1B10 showed much better diagnostic accuracy for HCC than AFP.…”

Clinical features and outcomes of hepatocellular carcinoma in Caucasian cirrhotic patients on long‐term analogue therapy for hepatitis B

“…This indeed is not what has been found in our patients who, in the vast majority of cases, presented with early, small, single HCC—as high as 92%, with 93% of our patients within “Milan criteria”—assuring the best treatment options (curative treatment options offered to 78% of our patients) and the best prognosis. This is an unprecedented finding for Caucasian cirrhotic patients as the only other similar, but smaller in size, studies came from Korea and Hong‐Kong . There are several possible explanations for this finding.…”

Should AFP (or Any Biomarkers) Be Used for HCC Surveillance?

“…Recent studies suggest the performance of AFP can be optimized by stratifying the population under surveillance by etiology, receipt of therapy for chronic viral hepatitis – which may influence hepatic inflammation and liver regeneration, and liver synthetic function as measured by serum albumin [13–15]. Further, recent studies also suggest that performance of liver US, which has been considered the more sensitive and specific screening modality, may not be as high in real-life practice as previously thought [16].…”