Positivity of high‐sensitivity HBsAg test, not previous HBV infection, indicates poor prognosis in patients with non‐HBV‐related HCC.

Summary: Background and Aims: The prognostic impact of previous‐HBV‐infection (pHBV) in non‐HBV‐related hepatocellular carcinoma (non‐HBV‐related‐HCC) and the prevalence, characteristics and significance of recently developed high‐sensitivity HBs antigen positivity (hHBsAg+) in these patients remain unclear. We aimed to close these gaps. Methods: We retrospectively screened patients with newly diagnosed non‐HBV‐related‐HCC (standard HBsAg‐test negative) at Hokkaido University. Patients with complete clinical information and preserved serum for hHBsAg+ were included. We evaluated the prevalence, characteristics and prognostic impact of pHBV and hHBsAg+ in non‐HBV‐related‐HCC. Results: A total of 401 non‐HBV‐related‐HCC patients were included (288 with pHBV/113 without pHBV). In non‐HBV‐related‐HCC, pHBV did not affect overall survival (OS). Among non‐HBV‐related‐HCC patients with pHBV, 11.8% (34/288) were hHBsAg+ and had more advanced stages of HCC, higher AFP levels, higher vascular invasion rates, and significantly shorter OS than others (OS: 19.3 vs. 61.4 months, p = 0.012). Comparison of OS among non‐HBV‐related‐HCC patients without pHBV (group 1), those with pHBV and without hHBsAg+ (group 2), and those with pHBV and hHBsAg+ (group 3) revealed significantly shorter OS in group 3 (19.3, 56.6 and 66.4 months in groups 1, 2 and 3, respectively; p = 0.036). Multivariate Cox regression indicated that compared with group 1, only group 3 was significantly and independently associated with shorter OS (HR: 2.044, p = 0.011). Subgroup analysis revealed that this association was particularly evident in non‐HBV‐related‐HCC patients with non‐B‐non‐C aetiology and advanced HCC. Conclusions: In non‐HBV‐related‐HCC patients, hHBsAg+, not pHBV, is significantly and independently associated with poor prognosis. [ABSTRACT FROM AUTHOR]