Early Versus Late Biliary Leakage After Hepatic Resection: Incidence, Risk Profiles, and Clinical Impact of Diagnostic Timing

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Background/Objectives: Post-hepatectomy biliary leakage (BL) remains a major source of postoperative morbidity. While traditional risk models treat BL as a single clinical entity, its chronological presentation follows distinct patterns that raise the hypothesis of distinct underlying pathophysiological mechanisms. This study aimed to stratify post-hepatectomy biliary fistulas into early and late onset to identify unique independent risk factors and clarify their separate risk profiles. Methods: This retrospective cohort study evaluated 370 patients who underwent hepatic resection between 2020 and 2024. BL was defined according to the International Study Group of Liver Surgery criteria. Based on the bimodal distribution of diagnostic timing within the cohort, patients were stratified by the postoperative day (POD) of diagnosis into Early Biliary Leakage (EBL, diagnosed on POD ≤ 7) and Late Biliary Leakage (LBL, diagnosed on POD > 7). Independent predictors were identified using binary and multinomial logistic regression models. Results: The overall incidence of BL was 9.7% (36/370), with diagnostic peaks occurring at PODs 3 and 11. EBL accounted for 55.6% of leaks, while LBL accounted for 44.4%. In multivariable analysis, an operative time exceeding 5 h was the sole independent global predictor for overall leakage (OR = 6.9; 95% CI 2.4–19.4; p < 0.001). For EBL, independent predictors were tumor proximity to major intrahepatic vessels (OR = 4.1; 95% CI 1.5–11.6; p = 0.007) and an operative time exceeding 5 h (OR = 5.2; 95% CI 1.4–19.2; p = 0.012). For LBL, an operative time exceeding 5 h was the single independent predictor, carrying a substantial risk (OR = 12.2; 95% CI 2.6–56.7; p = 0.001). Histologically, cholangiocarcinoma was significantly overrepresented in the leakage cohort compared to non-leak patients (41.7% vs. 11.7%; p = 0.05). Conclusions: Stratifying post-hepatectomy biliary leakage by diagnostic timing highlights critical differences in patient pathways and hospital readmission rates. While EBL are identified during the initial stay, LBL present insidiously after an uneventful first week, causing a higher 30-day readmission rate (62.5% vs. 30.0%, p = 0.091). Clinical surveillance and patient education at discharge are essential to identify late biliary complications early.

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