Biomarkers for hepatic sinusoidal obstruction syndrome after hematopoietic cell transplantation

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Hepatic sinusoidal obstruction syndrome (SOS), previously known as veno-occlusive disease, is one of the major complications during the early period after hematopoietic cell transplantation (HCT). The disease is caused by toxic injury of conditioning therapy to sinusoidal endothelial cells, initiating the clinical symptoms of hyperbilirubinemia, tender hepatomegaly, ascites, and weight gain. The incidence and severity of SOS have decreased significantly in recent years, but fatal outcomes of SOS are still observed in clinical practice [1]. SOS has no diagnostic biomarkers, and its diagnosis is depends on clinical criteria. Moreover, the severity of SOS is defined retrospectively, based on the clinical outcome. Single or combinations of parameters have been investigated for their potential as biomarkers for the diagnosis or prognosis of SOS. Genetic polymorphisms were associated with the occurrence of SOS in several studies. Glutathione S-transferase (GST) is a family of phase II detoxification enzymes that catalyze the conjugation of glutathione to various xenobiotics. Polymorphisms of GST genes have significant influence on the pharmacokinetic parameters of busulfan, which is commonly used in conditioning regimens for HCT. Of 114 patients with -thalassemia majorundergoing HCT, those with GSTM1-null genotypes had significantly higher incidences of hepatic SOS compared with those with GSTM1-present genotype (46.5% vs. 18.3%; P =0.001) [2]. Heparanase (HPSE) is an enzyme that cuts the saccharide chains of heparin sulfate proteoglycans, interacts with binding proteins, and activates signaling components. Genetic polymorphisms of HPSE (rs4693608 and rs4364254) were significantly associated with the incidence of hepatic SOS in 160 children undergoing allogeneic HCT for malignant and non-malignant diseases [3]. Methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes involved in homocysteine metabolism. The C677T and A1298C gene polymorphisms in MTHFR correlate with MTHFR enzyme activity. MTHFR haplotype 677CC/1298CC was significantly associated with the development of hepatic SOS in 62 adult patients with acute myeloid leukemia receiving myeloablative conditioning regimen (busulfan plus cyclophosphamide) for HCT [4]. Interleukin (IL)-1 is involved in the pathophysiology of graft-versus-host diseases, likely through the initiation and maintenance of host tissue inflammation as well as donor cell inflammatory response. IL-1 is a pro-inflammatory cytokine secreted by epithelial tissues early in the inflammatory response. The association of both patient and donor genotypes at the IL-1-511 C/T polymorphic site with hepatic SOS and mortality was investigated in 76 children undergoing HLA matched myeloablative allogeneic …