Improved Performance of Serum Alpha-Fetoprotein for Hepatocellular Carcinoma Diagnosis in HCV Cirrhosis with Normal Alanine Transaminase

Abstract

Background The utility of alpha fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is controversial. We aimed to identify factors associated with elevated AFP and define the patients for whom AFP is effective for surveillance. Methods Data from the National Cancer Institute Early Detection Research Network Phase 2 HCC biomarker study (233 early stage HCC and 412 cirrhotic patients) were analyzed. We analyzed 110 early stage HCC and 362 cirrhotic HCV patients for external validation. Sensitivity, specificity and area under the ROC curve (AUC) for HCC were calculated. Results HCV etiology, Non-White race, and serum alanine transaminase (ALT) predicted elevated AFP in cirrhotics. Non-White race and ALT predicted elevated AFP in HCC patients. Higher AUC of AFP for HCC was noted in patients with HBV (0.85) and alcohol (0.84) while it was lower in patients with HCV (0.80) and Non-viral/Alcohol etiology (0.76). The AUC was higher in HCV patients with serum ALT ≤ 40 U/L than patients with serum ALT>40 U/L (0.91 vs 0.75, P<0.01). At 90% specificity, the sensitivity of AFP increased from 44% to 74% in Whites with HCV and from 50% to 85% in Non-Whites with HCV. There was a trend towards higher AUC in HCV patients with serum ALT≤40 U/L than those with serum ALT>40 U/L (0.79 vs 0.69, P=0.10) in the validation cohort. Conclusions The satisfactory performance of AFP in HCV patients with normal ALT should be further validated. Impact The AFP may serve as a valuable surveillance test in HCV patients with normal ALT.

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

“…The accuracy of AFP in HCC surveillance has been shown to improve with measuring an increasing trend of AFP rather than a one-time assessment [32]. Additionally, accounting for other patient factors such as ALT level and etiology of liver disease in assessing AFP result can substantially aid interpretation [13, 35, 14]. Newer statistical approaches that use prior AFP levels in a longitudinal manner, such as the parametric empirical Bayesian (PEB) screening algorithm, also show promise in enhancing the performance of AFP [57, 58].…”

GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score

“…Elevation of AFP in the absence of HCC can often be seen in the presence of enhanced hepatocyte destruction and regeneration, particularly in patients with chronic viral hepatitis. Pregnant woman or patients with gonadal tumors may have falsely elevated AFP, which limits its utility as a surveillance test (17,18).…”

Minimal increases of serum alpha‐foetoprotein herald HCC detection in Caucasian HBV cirrhotic patients under long‐term oral therapy

“…The role of serum AFP in HCC surveillance has been debated for a long time and, because of its suboptimal sensitivity and specificity, it has been excluded for a long time from several national and international HCC guidelines . However, nowadays HBV represents a unique clinical setting because third‐generation NUCs maintained viral suppression, shutting down liver inflammation, thereby maximize AFP specificity for early HCC detection, as well as recently showed in HCV cirrhotics cohorts cured by direct‐acting antivirals . Only two of the four previous Asian studies evaluating AFP‐HCC relationship in HBV cohorts enrolled patients treated with high genetic barrier‐to‐resistance NUC (ETV) .…”