Serum YKL-40 in young patients with β-thalassemia major: relation to iron overload, hepatitis C virus infection and liver cirrhosis

Abstract

SUMMARY B eta thalassemia major is an inherited disease resulting from reduction or total lack of beta globin chains. Patients with this disease need repeated blood transfusion for survival. This may cause oxidative stress and tissue injury due to iron overload, altered antioxidant enzymes, and other essential trace element levels. YKL-40, a highly conserved glycoprotein belonging to the family of glycosyl hydrolase 18, is a lectin that binds heparin and chitin. YKL-40 is an inflammatory glycoprotein expressed by infiltrating macrophages in various inflammatory conditions and involved in endothelial dysfunction by promoting chemotaxis, cell attachment and migration, reorganization and tissue remodelling as a response to endothelial damage. Several studies have found elevated YKL-40 concentrations in sera of patients with liver diseases, such as hepatic fibrosis by HCV. Therefore, we determined the serum YKL-40 among young patients with β-TM and assessed its relation to markers of hemolysis, iron overload and liver fibrosis as well as various hemolysis-associated complications. This study included 50 β-TM patients (19 males and 31 females) recruited from the regular attendants of the Pediatric Hematology Clinic, Pediatric Hospital, Ain Shams University. Patients were compared with 35 age- and sex-matched healthy subjects (14 males and 21 females) enrolled as controls. The mean age of thalassemia patients was 13.8 ± 2.7 years (range: 5-18 years) while that of controls was 13.2 ± 4.9 years (range: 4-18 years). All included patients were subjected to detailed medical history and thorough clinical examination with special emphasis on anthropometric measures, disease duration, evidence of renal, hepatic or cardiac disease, history of splenectomy, transfusion history and chelation therapy. YKL-40 levels were measured by enzyme linked immunosorbent assay (ELISA). The mean disease duration was 12.5 ± 2.6 years (range: 4.2-17 years). It was observed that 60% of patients were splenectomized and 48% had hepatitis C virus infection while 30% had heart disease. Liver cirrhosis (TE values > 12.5kPa) was encountered in 32% while variable degrees of liver fibrosis were observed in 68% of studied thalassemia patients. HCV-positive patients had significantly higher WBCs count, ALT and serum ferritin than HCV-negative patients. Liver stiffness using transient elastography was slightly increased among patients with HCV infection than the negative group although no significant difference was found between both groups. In the current work, YKL-40 levels were significantly higher in β-TM patients compared with control group. YKL-40 was significantly higher among patients with heart disease than those without. ROC curve analysis revealed that the cutoff value of YKL-40 at 1500 pg/mL could differentiate patients with and without heart disease with high sensitivity and specificity.