Serum calcium and liver injury in people living with HIV: a longitudinal cohort study in Southeast China

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Background Liver disease remains a major cause of non-AIDS-related morbidity and mortality in people living with HIV (PLWH). Calcium homeostasis is involved in multiple hepatic processes, but the clinical relationship between serum calcium and liver injury in PLWH remains unclear.Methods We conducted a retrospective longitudinal cohort study incorporating repetitive measurements and proteomic analysis. Associations between serum calcium and liver disorders were assessed using logistic regression, Cox regression, and piecewise linear regression models.Results Among 2,726 patients with 10,621 blood samples over median 2.9-year follow-up, U-shaped relationships were observed between serum calcium and liver dysfunction/injury incidence, with a threshold corresponding to approximately 2.26 mmol/L (Ca × 2 = 4.52). In repetitive measurement analysis, serum calcium showed negative and positive associations with liver outcomes within Ca × 2 < 4.52 and ≥4.52 ranges, respectively (p < 0.05). In longitudinal analysis, patients with baseline Ca × 2 ≥ 4.52 had significantly increased adjusted risks of liver dysfunction (2.02, 95% CI: 1.33–3.07) and liver injury (4.61, 95% CI: 1.86–11.45) compared to Ca × 2 < 4.52. Each baseline Ca × 2 increase independently associated with 2.36-fold increased liver dysfunction risk (p < 0.05). Unadjusted models and Kaplan-Meier analysis showed consistent results. Proteomic analysis identified F5, GDI2, and LDHA significantly associated with both serum calcium and liver function, enriched in coagulation and glycolysis pathways.Conclusions Elevated serum calcium at combined antiretroviral therapy (cART) initiation strongly correlates with subsequent liver disorders in PLWH with Ca × 2 ≥ 4.52, potentially involving dysregulated coagulation and glycolysis pathways. These reference levels can guide assessment of calcium intake strategies in PLWH.

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