Inflammatory spectrum of frailty: Association between the systemic immune-inflammation index and frailty in liver transplant candidates.

Abstract

Systemic inflammation is a central feature of advanced chronic liver disease (AdvCLD). However, the relationship between inflammatory status, as reflected by the systemic immune-inflammation index (SII), and frailty in this population remains undefined. We performed a retrolective analysis of a prospective cohort of 291 patients with AdvCLD evaluated for liver transplantation (LT). Frailty was assessed using the Liver Frailty Index (LFI), gait speed test (GST) and the 6-minute walk test (6MWT). The SII, calculated as (platelets x neutrophils) / lymphocytes. Patients were categorized into low and high SII groups. Associations between SII and frailty were examined using multivariable logistic and linear regression. The prognostic value of SII for one-year all-cause mortality was evaluated using a competing-risk model with LT as the competing event. Among 291 patients, 46 (16%) met criteria for LFI ≥ 4.5, and 56 (19%) had a 6MWT <250 m. High SII (≥3.52) was associated with higher MELD 3.0 scores, greater LFI ≥ 4.5 prevalence (23% vs. 9%), slower GS (0.8 m/s vs 1.0 m/s) and a higher proportion walking <250 m (27% vs 12%). Median SII increased progressively across LFI categories and was significantly higher in individuals walking <250 m. High SII remained independently associated with frailty (LFI ≥ 4.5), 6MWT <250 m and GST in multivariable models. After MELD 3.0 adjustment, high SII was associated with increased mortality (aSHR 2.74; 95% CI 1.18-6.33). SII reflects systemic inflammation, and higher SII values are associated with increased frailty and higher mortality in AdvCLD.