HLA-C*04 and hepatocellular carcinoma post-surgical survival in Hawaii

Background The role of human leukocyte antigen (HLA) allotype in hepatocellular carcinoma (HCC)-specific outcomes is poorly understood. Methods We performed a retrospective analysis of patients with HCC treated surgically in Hawaii at a single, tertiary care institution. HLA allotyping was performed as clinically indicated for patients undergoing orthotopic liver transplantation (OLT), and commercial HLA genotyping was performed on PBMCs collected from patients who underwent partial hepatectomy (PH). The relationship of HLA with overall survival (OS) was evaluated by univariable and multivariable Cox proportional hazards models. Results From 2012 to 2024, 84 patients underwent OLT with HLA assessment (n = 43) or PH with banked PBMCs available for genotyping (n = 41). The median age was 62; there were 20% female patients; and 50% and 10% identified as Asian and Pacific Islander, respectively. Nearly 70% were BCLC 0 or A, and the median tumor size was 3 cm. HCC etiology was 19% NAFLD, 38% HBV, and 42% HCV. The multivariable model identified a history of non-HCC malignancies, tumor size, MELD score, and the presence of at least one germline allele of HLA-C*04 to be significantly correlated with worse postoperative OS ( p < 0.05). Conclusion Among an ethnically diverse population of mostly early-stage patients treated with OLT or PH in Hawaii, exploratory analysis showed that disease-specific factors and HLA-C*04 allotype were independently associated with worse postoperative OS. Based on this hypothesis-generating study, future studies should evaluate whether the unique properties of Hawaii’s HCC surgical population include an immuno-genomic mechanism affecting outcome.