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Background This study aimed to investigate the association between relative handgrip strength and frailty among adults with liver diseases.Methods Participants aged ≥45 years with liver diseases were identified from the China Health and Retirement Longitudinal Study. Relative handgrip strength was calculated as the maximum dominant-hand grip strength divided by body mass index and standardized by sex. Frailty was defined as a frailty index score ≥25. Wave 1–3 data were used as baseline, and participants were followed up through wave 5. Cox proportional hazards models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for potential covariates. Restricted cubic splines (RCS) were used to assess potential nonlinear associations.Results A total of 657 participants with liver diseases were included, with a median follow-up of 49 months. Each one-unit increase in relative handgrip strength was associated with a 40% lower risk of frailty (HR = 0.60, 95% CI: 0.41–0.87). When relative handgrip strength was categorized into tertiles, compared with the lowest tertile, the middle tertile was associated with a 61% lower frailty risk (HR = 0.39, 95% CI: 0.15–0.98), and the highest tertile was associated with an 84% lower frailty risk (HR = 0.16, 95% CI: 0.06–0.44). RCS analysis indicated a significant overall association with frailty (P for overall = 0.03) and no evidence of nonlinearity (P for nonlinearity = 0.90, IDDF2026-ABS-0065 Figure 1. Restricted cubic spline analysis of the association between relative handgrip strength and frailty in adults aged ≥45 years with liver disease).Conclusions Higher relative handgrip strength was independently associated with a reduced risk of frailty among adults with liver diseases. This finding supports the use of relative handgrip strength as a simple marker for identifying individuals at high risk of frailty and for guiding muscle-strengthening interventions in this population.Abstract IDDF2026-ABS-0065 Figure 1