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.