To the editor, We read with great interest the study by Singal et al. and commend the authors for this large prospective cohort study. [1] The authors concluded that single point as well as longitudinal GALAD (Gender, Age, L3 fraction of alpha-fetoprotein [AFP-L3], alpha-fetoprotein [AFP], des-gamma carboxy prothrombin [DCP]) score has high sensitivity for early HCC detection when compared with individual component biomarkers of GALAD score and HCC early detection screening (HES).HCC has a significant benefit in prognosis with a surveillance program due to effective treatment when caught early. The current guidelines suggest use of abdominal ultrasound (US) with or without AFP for HCC surveillance. US has been criticized for operator dependence and decrease in sensitivity with obesity, NAFLD, and small tumor, particularly <2 cm. [2] For the requirement of a screening modality with better sensitivity, reproducibility, and accessibility, a blood-based biomarker was suggested. A recent Cochrane meta-analysis has shown that US is superior to AFP for resectable HCC and the combination outperforms them individually, with sensitivity reaching up to 89% and specificity up to 87%. [3] In a resource-poor setting, cost becomes a major factor; the addition of multiple biomarkers increases the cost of surveillance, and no cost-benefit analysis for GALAD score is available yet. Further, the morbidity attached with high false positivity rate (FPR) of 25% with the GALAD score can be alarming compared with 15% with US and AFP combination. [3,4] When adjusted for FPR, GALAD score does not outperform AFP-L3 or HES. [4] Recently, an USfree approach has been deemed to be a way forward with the availability of newer biomarkers and their combinations. Addition of DCP alone to AFP raises the sensitivity of detecting HCC to around 75% with a specificity >90% in a cohort of patients with chronic hepatitis B. [5] This combination was not compared in this study with GALAD and would be useful because this will reduce the cost of surveillance. A screening test should balance availability, affordability, and accuracy for its appropriate usage, and GALAD score may not fulfill this role in current practice. PATIENT AND PUBLIC INVOLVEMENTPatients and/or the public were not involved in the design, conduct, reporting, or dissemination of plans for this research.
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