Serum Cytokeratin-18 as a Noninvasive Biomarker of Hepatocellular Injury in Patients with β-thalassemia

BACKGROUND: Chronic transfusion therapy in β-thalassemia causes progressive iron overload and oxidative hepatocellular injury. Conventional markers, such as serum ferritin and aminotransferases, are limited by their lack of specificity, highlighting the need for reliable, noninvasive biomarkers of hepatic necrosis. OBJECTIVE: To evaluate serum cytokeratin-18 (CK-18) as a biomarker of hepatocellular injury in patients with β-thalassemia and to compare its levels between transfusion-dependent β-thalassemia (TDT) and non-transfusion-dependent β-thalassemia (NTDT) cohorts. MATERIALS AND METHODS: We conducted a cross-sectional study that enrolled 160 patients with confirmed beta-thalassemia (130 TDT and 30 NTDT) at the Hereditary Blood Disorder Center, Karbala Teaching Hospital for Maternity and Children (November 2024–December 2025). Serum CK-18, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and ferritin levels were measured. We used an independent samples t -test and Pearson correlation analysis. RESULTS: TDT patients exhibited significantly higher serum concentrations of CK-18 (353.9 ± 189.4 vs. 64.1 ± 20.7 pg/mL; P < 0.01), ferritin (2566.3 ± 1873.5 vs. 134.2 ± 115.5 ng/mL; P < 0.01), and all liver enzymes than NTDT patients. CK-18 concentration significantly correlated with those of ALT ( r = 0.388), AST ( r = 0.384), ALP ( r = 0.264), and ferritin ( r = 0.415; all P < 0.01). Patients with elevated liver enzyme levels had substantially higher CK-18 concentrations than those with normal enzyme levels ( P < 0.01). CONCLUSION: Serum CK-18 levels were significantly elevated in transfusion-dependent β-thalassemia and consistently correlated with established hepatic injury markers, confirming its utility as a sensitive, noninvasive indicator of ongoing hepatocellular death.