AbstractBackgroundWe sought to investigate the prognosis of patients following curative‐intent surgery for intrahepatic cholangiocarcinoma (ICC) stratified by hepatitis B (HBV‐ICC), hepatolithiasis (Stone‐ICC), and no identifiable cause (conventional ICC) etiologic subtype.Methods986 patients with HBV‐ICC (n = 201), stone‐ICC (n = 103), and conventional ICC (n = 682) who underwent curative‐intent resection were identified from a multi‐institutional database. Propensity score matching (PSM) was used to mitigate residual bias.ResultsHBV‐ICC patients more often had cirrhosis, earlier stage tumors, a mass‐forming lesion, well‐to‐moderate tumor differentiation, and an R0 resection versus stone‐ICC or conventional ICC patients. Five‐year recurrence‐free survival among HBV‐ICC and conventional ICC patients was 23.9 and 17.8%, respectively, versus a recurrence‐free of only 8.3% among patients with stone‐ICC. Similarly, 5‐year overall survival among patients with stone‐ICC was only 18.3% compared with 48.9 and 38.0% for patients with HBV‐ICC and conventional ICC, respectively. On PSM, patients with stone‐ICC group had equivalent long‐term outcomes as HBV‐ICC patients. In contrast, on PSM, stone‐ICC patients had a median overall survival of only 18.0 months versus 44.0 months for patients with conventional ICC. Median overall survival after intrahepatic‐only recurrence among patients who had stone‐ICC (6.0 months) was worse than OS among HBV‐ICC (13.0 months) or conventional ICC (12.0 months) (p = 0.006 and p = 0.082, respectively).ConclusionsWhile HBV‐ICC had a better prognosis on unadjusted analyses, these differences were mitigated on PSM suggesting no stage‐for‐stage differences in outcomes compared with stone‐ICC or conventional ICC. In contrast, patients with stone‐ICC had worse long‐term outcomes. These data highlight the relative importance of ICC etiology relative to established clinicopathological factors in the prognosis of patients with ICC.