Clinical Significance of Alpha-Fetoprotein in Alpha-Fetoprotein Negative Hepatocellular Carcinoma Underwent Curative Resection

Abstract

Background The clinical value of alpha-fetoprotein (AFP) in patients with AFP-negative (< 20 ng/ml) hepatocellular carcinoma (HCC) who underwent curative resection remained controversial. Aims To investigate clinical relevance and prognostic effect of preoperative serum AFP level in this subgroup. Methods A total of 1879 patients with AFP-negative HCC who underwent curative resection were included in the study. Overall survival (OS) and disease-free survival (DFS) rate were displayed by Kaplan–Meier method and compared by log-rank test. Multivariate cox proportional hazard regression analysis was used to identify the independent prognostic factors. The prognostic predictive performance was analyzed by time-dependent areas under receiver operating characteristic curve (AUC). Results Even in AFP-negative HCC, patients with high preoperative serum AFP level tended to have multiple tumor ( P < 0.001), poorer differentiation of tumor cell ( P < 0.001), presence of satellite nodules ( P < 0.001), and MVI ( P = 0.002). Kaplan–Meier analysis showed the adverse impact of AFP level on prognosis, especially for DFS. Multivariate analysis identified AFP as the independent unfavorable factor for OS and DFS ( P < 0.001 for both). Time-dependent AUC analysis showed that the combination with AFP could improve the prognostic predictive performance of 8th AJCC and BCLC staging system. Conclusions AFP was still the surrogate of aggressive behavior of HCC and independent prognostic factor for patients with AFP-negative HCC underwent curative resection. Even combining with such a low level of AFP could significantly improve the predictive performance of conventional staging system. Supplementary Information The online version of this article (10.1007/s10620-020-06797-z) contains supplementary material, which is available to authorized users.

Inflammation-Related Marker NrLR Predicts Prognosis in AFP-Negative HCC Patients After Curative Resection

“… 26 Even in AFP-negative HCC patients, AFP was still an independent prognostic factor. 6 We also found that AFP was associated with recurrence in AFP-negative HCC patients.…”

“…2,3 Many serum biomarkers have been used for diagnosis and treatment of HCC. [4][5][6][7] Alpha-fetoprotein (AFP) is the most widely used serum biomarker for HCC in diagnosis and surveillance. 8 Elevated AFP is associated with aggressive tumor features and poor prognosis.…”

Impact of portal‐phase signal intensity of dynamic gadoxetic acid‐enhanced magnetic resonance imaging in hepatocellular carcinoma

“…Univariate analysis revealed that the significant predictive factors for poorly differentiated HCC were AFP > 20 ng/mL, lens culinaris agglutinin‐reactive fraction of alpha‐fetoprotein (AFP‐L3) ≥ 10%, DCP ≥ 100 mAU/mL, tumor size ≥ 50 mm, microvascular invasion, intrahepatic metastasis, and SIRPP ≤ 0.85. We defined the SIRPP cutoff level using ROC analysis and the cutoff levels of AFP and DCP, according to previous reports 13,14 . Multivariate analysis revealed that the independent predictive factors for poorly differentiated HCC were AFP > 20 ng/mL (hazard ratio [HR]: 3.23, 95% confidence interval [CI]: 1.39–7.47, p = .0065) and SIRPP ≤ 0.85 (HR: 4.44, 95% CI: 1.9–10.4, p = .0006) (Table 1).…”

“…We defined the SIRPP cutoff level using ROC analysis and the cutoff levels of AFP and DCP, according to previous reports. 13,14 Multivariate analysis revealed that the independent predictive factors for poorly differentiated HCC were AFP > 20 ng/mL (hazard ratio [HR]: 3.23, 95% confidence interval [CI]: 1.39-7.47, p = .0065) and SIRPP ≤ 0.85 (HR: 4.44, 95% CI: 1.9-10.4, p = .0006) (Table 1). The rate of poorly differentiated HCC was 64% in the group with AFP > 20 ng/mL and SIRPP ≤ 0.85, 24% in the group with AFP ≤ 20 ng/mL and SIRPP ≤ 0.85, or AFP > 20 ng/mL and SIRPP > 0.85, and 10% in the group with AFP ≤ 20 ng/mL and SIRPP > 0.85.…”

Hepatocellular Carcinoma: Systematic Review of Relevant Biomarkers and the Impact on Liver Resections

“…Biomarkers such as α-fetoprotein (AFP) are associated with a more aggressive tumour phenotype and higher recurrence risk after surgical resection, while a significant proportion of patients do not present elevation of AFP serum levels [8,9] . About 30-40% of the patients with HCC present low levels (<20 ng/ml) of this biomarker, however, even in these cases AFP levels are correlated with a poorer differentiation of the tumour, microvascular invasion, presence of satellite nodules and disseminated intrahepatic metastasis [9,10] .…”