Attenuation trend of alpha-fetoprotein predicts postoperative prognosis in alpha-fetoprotein-positive hepatocellular carcinoma patients.

[BACKGROUND] Although preoperative alpha-fetoprotein levels predict hepatocellular carcinoma prognosis, the significance of perioperative alpha-fetoprotein dynamics remains unclear.

[METHODS] We analyzed 238 alpha-fetoprotein-positive hepatocellular carcinoma patients undergoing curative hepatectomy (2016-2023). The alpha-fetoprotein half-life was derived from preoperative alpha-fetoprotein levels, postoperative serial alpha-fetoprotein measurements, and the intervals between assessments. Interindividual variability in serum alpha-fetoprotein half-life (median of approximately 4 days) was observed among patients with elevated alpha-fetoprotein levels. Consequently, patients were stratified into rapid alpha-fetoprotein decay (≤4 days) and delayed alpha-fetoprotein decay (>4 days) groups based on this threshold. Clinicopathologic characteristics and survival outcomes were compared between the cohorts. Univariate and multivariate Cox proportional hazards models were used to identify independent risk factors for postoperative hepatocellular carcinoma recurrence. Propensity score matching was implemented to address baseline clinicopathologic disparities. The primary endpoint was recurrence-free survival.

[RESULTS] Patients with hepatocellular carcinoma and preoperative alpha-fetoprotein levels >100 ng/mL exhibited significantly worse postoperative prognosis compared with those with lower alpha-fetoprotein levels. The delayed alpha-fetoprotein decay group demonstrated advanced China liver cancer stage, higher incidence of microvascular invasion, larger tumor diameters, and elevated preoperative serum alpha-fetoprotein levels. Consequently, the delayed alpha-fetoprotein decay group showed significantly inferior recurrence-free survival and overall survival compared with the rapid alpha-fetoprotein decay group. Multivariate Cox analysis confirmed prolonged alpha-fetoprotein half-life as an independent recurrence risk factor (hazard ratio = 1.653, 95% confidence interval: 1.165-2.346, P = .005).

[CONCLUSION] Prolonged alpha-fetoprotein half-life was associated with advanced tumor stage and aggressive tumor behavior in patients with hepatocellular carcinoma, suggesting a poor prognosis after curative resection.