Relationship between post-ablation fever and prognosis in initial hepatocellular carcinoma: A 15-year multicenter, retrospective cohort study

Background: Fever is a common side effect following thermal ablation in patients with hepatocellular carcinoma (HCC), yet its impact on prognosis remains unclear. Materials and Methods: This retrospective study included initial HCC patients who underwent US-guided percutaneous microwave ablation at 13 hospitals between January 2006 and February 2021. All patients were categorized into afebrile, transient low-grade fever (TLF), and prolonged or high-grade fever (PHF) groups. Primary outcomes included very early recurrence (VER) and early recurrence (ER), secondary outcomes were disease-free survival (DFS) and overall survival (OS). Fever cut-offs for VER/ER were established using restrictive cubic splines and adjusted Cox model. Survival analyses used the Kaplan-Meier method. Results: A total of 1458 initial HCC patients (mean age, 59±11[SD]; 1146 men). Compared to afebrile individuals, patients with TLF (temperatures ranging 37.0-38.8°C for 1-2 d), showed independent protective effects against VER (HR, 0.73; 95% CI: 0.57,0.95; P =0.02) and ER (HR, 0.66; 95% CI: 0.54,0.81; P <0.001), however, PHF showed no differences in VER (HR, 0.99; 95% CI: 0.76,1.30; P =0.96) and ER (HR, 0.86; 95% CI: 0.69,1.07; P =0.17). With a median follow-up of 47 months (IQR:26-79), the median DFS for TLF patients was 40 months, superior to afebrile (30 mo, P =0.019) and PHF patients (33 mo, P =0.049). The 5-year OS rate for TLF patients was 73.2%, higher than afebrile (69.3%, P =0.02) and PHF patients (66.7%, P =0.03). No significant difference was found in DFS and OS between afebrile and PHF patients ( P =0.90 and 0.71). Notably, TLF patients exhibited the highest lymphocyte counts increasing median 7 days after ablation ( P <0.001 vs. afebrile and P =0.01 vs. PHF). Conclusion: Transient low-grade fever following percutaneous microwave ablation in hepatocellular carcinoma patients demonstrated protection against early recurrence, possibly attributed to the short-term activation of lymphocytes.