Re-evaluating the diagnostic value of α-fetoprotein for hepatocellular carcinoma in the direct-acting antiviral era.

Journal: Cancer

Study type: Retrospective single-center analysis of 388 patients who underwent curative hepatectomy for hepatocellular carcinoma (HCC).

Objective: To reassess the diagnostic performance and optimal cutoffs of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) for HCC in the contemporary era, characterized by widespread use of direct-acting antivirals (DAAs) for hepatitis C and a shift toward more nonviral HCC.

Methods:

  • – Included 388 consecutive patients undergoing curative resection.
  • – “Baseline” (postoperative) tumor marker levels were defined using measurements 4 months after surgery in patients who remained recurrence-free at 1 year (n=257), serving as non-HCC reference values.
  • – Patients were divided into pre-DAA and post-DAA eras.
  • – Diagnostic accuracy of AFP and DCP for HCC was evaluated by AUROC.
  • – Multivariable analyses assessed predictors of higher baseline AFP, focusing on fibrosis stage and HCV virologic status.

Key results:

  • – Baseline AFP levels were significantly lower in the post-DAA era: median 3 ng/mL (IQR 2–4) vs 4 ng/mL (IQR 3–7) pre-DAA (p < .001).
  • – AFP diagnostic performance improved: AUROC increased from 0.702 (pre-DAA) to 0.793 (post-DAA) (p = .014).
  • – DCP diagnostic performance remained essentially unchanged across eras.
  • – Etiology shifted: HCV-related HCC decreased from 30% to 20% (p = .012); nonviral HCC increased from 58% to 66% (p = .093).
  • – Lack of sustained virologic response (HCV non-SVR) and advanced fibrosis were independently associated with higher baseline AFP.
  • – Data support an updated AFP cutoff of 5 ng/mL for HCC detection; the conventional DCP cutoff of 40 mAU/mL remains appropriate.

Clinical implications:

  • – In the current treatment era, lower background AFP levels (due to viral clearance and reduced hepatic inflammation) enhance the specificity and overall diagnostic performance of AFP for HCC.
  • – Using an AFP threshold of 5 ng/mL, alongside a DCP cutoff of 40 mAU/mL, is supported for contemporary surveillance and diagnostic practice in post-hepatectomy and broader HCC populations.

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