Commentary: post-ablation fever as a prognostic signal after HCC ablation – merits, limits, and next steps

Dear Editor, We read with great interest the recent article by Cai et al[1], entitled “Relationship between postablation fever and prognosis in initial hepatocellular carcinoma: a 15-year multicenter, retrospective cohort study.” Building on a multicenter cohort with long-term follow-up, the authors examined the association between post-ablation fever and oncologic outcomes in patients undergoing initial thermal ablation for hepatocellular carcinoma. They reported that, compared with “no fever” or “persistent/high-grade fever,” a “transient low-grade fever” was statistically associated with a reduced risk of early recurrence and improved disease-free and overall survival. Notably, perioperative inflammatory and lymphocytic dynamics provided a biologically plausible signal supporting this association. Given that body temperature monitoring is universally available and low-cost, these findings – if externally confirmed – may offer a simple signal for postoperative risk stratification, although they are not yet sufficient to guide treatment decisions. From a methodological standpoint, instead of a binary fever classification, the authors jointly considered temperature intensity and duration, explored nonlinear effects using restricted cubic splines, and applied multivariable adjustment and inverse probability of treatment weighting to mitigate confounding. Subgroup analyses further suggested that the association was generally consistent across strata. These analytical choices are more refined than those in prior descriptive reports and likely reduce model-specification bias while improving interpretability. Nonetheless, several caveats merit cautious interpretation. First, the inherent limitations of retrospective design persist; despite weighting, residual confounding and information bias cannot be excluded. Second, temperature acquisition likely varied across centers in both frequency and precision, and the study did not provide direct evidence disentangling infection, sterile inflammation, and immune activation. Third, the findings were derived from treatment-naïve ablation-eligible patients; their applicability to patients receiving repeated locoregional therapy or systemic treatment remains uncertain. Future studies may consider: (i) prospective validation with pre-specified temperature acquisition and adjudicated infection assessment; (ii) integration of peripheral immune phenotypes, cytokine signatures, or microenvironmental readouts to determine whether “transient low-grade fever” reflects a specific immune-activation program rather than nonspecific inflammation; and (iii) exploration – under rigorous ethical and safety controls – of whether this phenotype could serve as a stratifying condition to time perioperative immuno-targeted interventions, ideally tested in randomized or quasi-experimental frameworks. In summary, this study provides a systematic evaluation of a common and often overlooked postoperative phenomenon, suggesting that temperature trajectories may carry adjunctive information for post-ablation management. The conclusions, however, require confirmation by higher-level evidence and mechanistic studies before they can be incorporated into clinical decision-making[2].