Association between the Prognostic Nutritional Index and survival outcomes in hepatocellular carcinoma patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced hepatocellular carcinoma (HCC), but substantial heterogeneity in treatment response and survival remains. The Prognostic Nutritional Index (PNI), reflecting both nutritional status and systemic immune function, has been increasingly investigated for its association with survival outcomes in the immunotherapy setting. However, existing studies have reported inconsistent results, possibly due to differences in patient populations, treatment strategies, and methodological factors. Therefore, we conducted an updated systematic review and meta-analysis to clarify the prognostic value of PNI in HCC patients receiving ICIs. Methods: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang Data databases were systematically searched from inception to April 18, 2026. Studies were included according to a predefined PICOS (Population, Intervention//Exposure, Comparison, Outcome, and Study Design) framework: adult HCC patients receiving ICI-based therapy, baseline PNI assessment before treatment, comparison between high- and low-PNI groups using study-defined cut-offs, and reported multivariable-adjusted hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS). A random-effects model was used to calculate pooled HRs with their 95% confidence intervals (CIs) for OS and PFS and study quality was evaluated using the Quality in Prognosis Studies (QUIPS) tool. Results: Fourteen studies including 3,341 HCC patients treated with ICIs were included. Pooled analyses showed that higher PNI was significantly associated with improved OS [hazard ratio (HR) =0.60, 95% confidence interval (CI): 0.48-0.75] and PFS (HR =0.72, 95% CI: 0.57-0.91). Substantial heterogeneity was observed for OS and moderate heterogeneity for PFS. Subgroup analyses showed that the association remained generally consistent across most studies. Importantly, similar effect estimates were observed in both low-risk and moderate-risk studies, suggesting that study quality did not materially influence the pooled results. Based on the QUIPS assessment, 10 studies were judged to be at low overall risk of bias and 4 at moderate risk, with the main concerns related to confounding, study participation, attrition, and statistical reporting. Conclusions: For advanced HCC patients receiving ICI therapy, higher pretreatment PNI was associated with improved survival outcomes in HCC patients receiving ICI-based therapy. Because the available evidence was derived mainly from retrospective studies, these findings should be interpreted cautiously and require prospective validation.