Impact of Serum Albumin Levels on Prognosis and Recurrence in Patients with Hepatocellular Carcinoma

Background: Liver function is a critical factor, both in the selection of treatment and in the prediction of prognosis in patients with hepatocellular carcinoma (HCC). The ALBI grade, introduced as a more objective method of assessing liver function, utilizes serum albumin (Alb) and total bilirubin (Bil) levels. Although albumin is widely recognized for its role in maintaining colloid osmotic pressure and regulating plasma volume, recent studies have implicated it in tumor progression, invasion, and metastasis. The purpose of this study is to determine the impact of serum albumin levels on overall survival (OS) and tumor invasion/metastasis in HCC patients with the same liver function (ALBI grade) at the time of diagnosis. Methods: In this study, 285 patients diagnosed with primary HCC at our institution from 2015 to 2019 were classified by ALBI grade and analyzed. Among them, 78 patients with ALBI grade 2 status were selected to evaluate the impact of albumin level. To further isolate the effect of albumin rather than bilirubin, patients in the ALBI grade 2 cohort were divided into two groups based on mean values of Alb (3.5 g/dL) and Bil (1.0 mg/dL). Alb normal group (Group A): Alb ≥ 3.5 g/dL, Bil ≥ 1.0 mg/dL (n = 42). Bil normal group (Group T): Alb < 3.5 g/dL, Bil < 1.0 mg/dL (n = 36). Liver function was almost the same in these two groups based on the ALBI grade. OS, progression-free survival (PFS), types of recurrence, and pathological findings were compared between the two groups. OS was analyzed by the log-rank test, and comparisons between the two groups were performed by the t-test and chi-square test, with p < 0.05 indicating statistical significance. Results: OS was significantly worse in Group T than in Group A before and after propensity score matching based on age, performance status, and HCC stage (p < 0.001 and p = 0.011). Among the 44 patients who received curative treatment (surgery or radiofrequency ablation), OS was also significantly worse in Group T (p < 0.001). An analysis of the recurrence patterns of 44 curatively treated patients revealed that Group T had significantly shorter PFS (p < 0.001), and all recurrence patterns were multiple (p = 0.002). Pathological analysis in 28 surgical patients showed that serosal invasion was present in significantly more patients in Group T (p = 0.003). Conclusions: Low serum albumin levels in patients with HCC indicate both liver dysfunction and increased tumor invasion and metastasis. Nutritional support and albumin supplementation may help reduce intrahepatic metastases and improve prognosis. Further studies are needed to explore the underlying mechanisms and therapeutic potential.