Alpha-fetoprotein still is a valuable diagnostic and prognosis predicting biomarker in hepatitis B virus infection-related hepatocellular carcinoma

Abstract

Use of serum alpha-fetoprotein (AFP) in clinical practices has been challenged in recent years, due to the lack of specificity and sensitivity. Here we conducted a retrospective study to evaluate the diagnostic and prognostic value of serum AFP among hepatocellular carcinoma (HCC) patients with their pathogenic features taken into consideration. The cohort for this study comprised 318 cases of hepatitis and 731 cases of cirrhosis, as well as 796 HCC patients. Using 11.62ng/mL as a cut-off value, the positive rate of AFP test among serum hepatitis B surface antigen (HBsAg) positive HCC patients was significantly higher than that in those HBsAg negative HCC patients (79.55% vs 56.49%, P < 0.000). Similarly, the median serum AFP level in HCC patients with serum HBsAg positive was significantly higher than that in those HBsAg negative HCC patients (423.89ng/ml vs 40.82ng/ml, P < 0.000). In addition, Kaplan-Meier curve analysis revealed that lower preoperative AFP level implicated a much higher overall survival rate. Of note, such prognosis predicting value was only seen in those chronic HBV infection-related HCC patients, but not among the HCC patients etiologically irrelevant to HBV infection. We believe that serum AFP is of diagnosis and prognostic predicting value for HCC with chronic HBV infection, and strongly suggest use of serum AFP as a biomarker in China and other HBV infection endemic area like Southeast Asia.

Keywords: Immune response; Immunity; Immunology and Microbiology Section; alpha-fetoprotein (AFP); diagnosis; hepatitis B virus; hepatocellular carcinoma.

Figure 1. Patients’ flowchart, data provided in absolute numbers

Figure 2. The receiver operating characteristic (ROC) curve of AFP in HCC diagnosis for all subjects

The points in the ROC curve indicate different AFP values with corresponding sensitivity and specificity, from which 11.62ng/mL was chosen as the cut-off value for AFP.

Figure 3. Cumulative post-surgery overall survival by different AFP levels among HCC patients with serum HBsAg positive (A) or with serum HBsAg negative (B)

A. Cumulative incidence of HCC with HBV by different AFP levels. Comparison of cumulative survival among (0∼20 ng/ml and >20ng/ml, 0∼200 ng/ml and >200ng/ml, 0∼400 ng/ml and >400ng/ml) subgroups of patients. The cumulative survival probability of the patients at 1, 3, and 5 years were 65.49%, 42.96% and 30.51% (0∼20 ng/ml, n = 168), 40.35%, 25.69% and 13.78% (>20ng/ml, n = 448), 57.48%, 39.39% and 26.31% (0∼200 ng/ml, n = 271), 36.37%, 22.86% and 11.77% (>200 ng/ml, n = 345), 56.4%, 39.50% and 24.48% (0∼400 ng/ml, n = 304), 35.10%, 20.71% and 11.94% (>400 ng/ml, n = 312) respectively. B. Cumulative incidence of HCC with non-HBV by different AFP levels. Comparison of cumulative survival among (0∼20 ng/ml and >20ng/ml, 0∼200 ng/ml and >200ng/ml, 0∼400 ng/ml and >400ng/ml) subgroups of patients. The cumulative survival probability of the patients at 1, 3, and 5 years were 56.97%, 31.02% and 21.59% (0∼20 ng/ml, n = 77), 49.51%, 39.06% and 32.36% (>20ng/ml, n = 103), 52.81%, 32.47% and 25.06% (0∼200 ng/ml, n = 114), 53.71%, 40.11% and 31.20% (>200 ng/ml, n = 66),54.22%, 34.65% and 28.77% (0∼400 ng/ml, n = 122), 50.59%, 37.25% and 26.08% (>400 ng/ml, n = 58) respectively.