AFP Thresholds for HCC Screening: Gastroenterology | March 2026

Introduction

Alpha-fetoprotein (AFP) remains the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance. Although AFP alone is insufficient for screening, its combination with ultrasound improves early HCC detection. However, the optimal AFP cutoff remains debated, particularly as the epidemiology of liver disease shifts from viral hepatitis toward metabolic and alcohol-related etiologies.

Summary

The traditional AFP threshold of 20 ng/mL should be lowered to 10 ng/mL for triggering diagnostic imaging in HCC surveillance. Using large datasets from the US Veterans Affairs (VA) system and the Organ Procurement and Transplantation Network (OPTN), found that lowering the AFP threshold improved sensitivity for HCC detection by 7–10%, with only a modest ~3% reduction in specificity. However, this increase in sensitivity also resulted in a 3–4% rise in false-positive results, leading to substantially more CT or MRI scans. In the VA cohort, lowering the threshold would have generated over 1000 additional imaging studies annually, with only a small proportion of HCC cases detected earlier.

Current guidelines recommend evaluating rising AFP levels, not just a single threshold value, which was not assessed in the analysis. Additionally, the OPTN dataset is biased toward early-stage HCC patients already undergoing treatment before transplant listing. Most importantly, the study did not demonstrate improved patient-centred outcomes such as earlier curative therapy or reduced mortality.

While lowering AFP thresholds may modestly increase detection rates, the authors caution that evidence is insufficient to justify immediate guideline changes. Future screening strategies may rely increasingly on multimarker panels (e.g., GALAD, HES) or emerging molecular biomarkers to improve early detection while minimising unnecessary testing.