Preoperative Zinc Deficiency as a Novel Prognostic Predictor for Postoperative Recurrence in Hepatocellular Carcinoma

Background/Objectives: The impact of preoperative zinc (Zn) status on the survival and recurrence of patients with hepatocellular carcinoma (HCC) after hepatectomy remains unclear. This study aimed to clarify whether preoperative Zn deficiency affects the prognosis of patients with HCC undergoing initial curative hepatectomy. Methods: We retrospectively reviewed 105 patients who underwent initial curative hepatectomy for HCC at our institution (2011–2018). Preoperative Zn deficiency was defined as serum Zn < 70 µg/dL. Clinical and tumor parameters were compared between patients with and without Zn deficiency. Disease-free and overall survival were evaluated using the Kaplan–Meier method, and prognostic factors were identified via univariate and multivariate Cox proportional hazards analyses. Subgroup analyses were conducted based on age, gender, and etiology. Results: Among 105 patients, 46 (43.8%) showed Zn deficiency (Zn deficiency group), whereas 59 (56.2%) showed normal Zn (normal Zn group). Compared with the normal-Zn group, the Zn deficiency group showed significantly lower hemoglobin, prothrombin activity, serum albumin, and smaller tumor size (all p < 0.05). The Zn deficiency group experienced significantly worse disease-free survival (p = 0.015) but no difference in overall survival (p = 0.63). On multivariate analysis, zinc deficiency (hazard ratio [HR] 1.83, p = 0.040) and prothrombin activity (HR 0.98, p = 0.042) were independent predictors of worse disease-free survival. Subgroup analysis revealed that Zn deficiency was significantly associated with elevated recurrence risk in patients with HCV-related liver disease (HR 3.67, p = 0.013). Conclusions: Preoperative Zn deficiency is an independent predictor of worse DFS after curative hepatectomy. Although further large-scale studies are required to confirm these findings, evaluating preoperative Zn status may help identify patients at high risk of HCC recurrence.