The Association of High Mobility Group Box-1 with Sepsis Susceptibility and Mortality Risk: A Meta-Analysis.

High mobility group box-1 (HMGB1) regulates inflammation, immune response, DNA repair, and cell death, which is crucial in the pathogenesis of sepsis; while its role in sepsis susceptibility and mortality risk remains inconsistent. Hence, this meta-analysis systemically investigated the dysregulation level of HMGB1 and its association with mortality risk. PubMed, Web of Science, Embase, and Cochrane Library databases were searched until May 2024. Studies written in English and comparing HMGB1 level in serum or plasma detected by enzyme-linked immunosorbent assay between adult sepsis patients and controls, or non-survivors and survivors of sepsis, were eligible. Twenty-eight studies containing 3,110 subjects were included. The quality of studies was satisfactory evaluated by the Newcastle-Ottawa scale. Pooled analyses showed that HMGB1 was increased in sepsis patients versus controls (P < 0.001). Subgroup analysis revealed that HMGB1 was increased in sepsis patients versus healthy controls (P < 0.001), but less varied between sepsis patients and non-sepsis controls (P = 0.081). Additionally, HMGB1 was elevated in non-survivors versus survivors of sepsis (P = 0.030). Publication bias existed in HMGB1 differences between sepsis patients and controls; but it was adjusted using the trim-and-fill method, and the statistical significance did not change after that. Sensitivity analysis indicated acceptable robustness. In conclusion, this study suggests the potential of HMGB1 to serve as a possible biomarker for sepsis diagnosis and mortality risk stratification.