Improving Recurrence Prediction in Intrahepatic Cholangiocarcinoma: The Synergistic Impact of the FIB-4 Index and Tumor Burden Score on Post-hepatectomy Outcomes

Background: The prognostic role of the fibrosis-4 (FIB-4) index relative to intrahepatic cholangiocarcinoma (ICC) after hepatectomy remains unclear. This study sought to characterize the impact of the FIB-4 index and tumor burden score (TBS) on recurrence and overall survival (OS). Methods: ICC patients undergoing hepatectomy (2000–2020) were identified using a multi-institutional database. Patients were categorized as low (low TBS/low FIB-4 index), intermediate (low TBS/high FIB-4 index or high TBS/low FIB-4 index), and high (high TBS/high FIB-4 index). Results: Among 1168 patients in different TBS and FIB-4 index cohorts, 3-year recurrence varied considerably. For instance, among the patients with low TBS, individuals with a high FIB-4 index had a greater risk of recurrence than patients with a low FIB-4 index (59.9 vs. 47.7%; P = 0.01). Among patients with a high TBS, individuals with a high versus a low FIB-4 index had a higher incidence of recurrence (76.8 vs. 69.0%; P = 0.04). A similar pattern was observed among patients with both a low FIB-4 index (low [47.7%] vs. high [69.0%] TBS) and a high FIB-4 index (low [59.9%] vs. high [76.8%] TBS; both P < 0.001). Patients with a high [27.5%] versus a low [48.8%] TBS; P < 0.001) and patients with a high [34.2%] versus a low [43.5%] FIB-4 index; P = 0.01) had a worse OS. The multivariable analysis demonstrated an increasing risk of recurrence in the intermediate-index (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.20–2.16; P = 0.001) and high-index (HR, 2.13; 95% CI 1.45–3.13; P < 0.001) groups versus the low-index group. Conclusions: Both tumor-related and non-tumorous characteristics should be used to predict risk of recurrence and survival more accurately among patients with ICC following hepatic resection.