SEN virus genotype H distribution in β-thalassemic patients and in healthy donors in Iraq: Molecular and physiological study

Abstract

The SEN virus (SENV) has been linked to transfusion-associated non-A-E hepatitis; however, information regarding SENV infections in patients with thalassemia, particularly in those with hepatitis virus co-infections, remains limited. This study investigated the frequency of SENV (genotypes D and H) infections in Iraqi patients with thalassemia who were and were not infected with hepatitis C virus (HCV). The study involved 150 β-thalessemia patients (75 with HCV infections and 75 without) and 75 healthy blood donors. Patient levels of vitamins C and E, liver function markers, and glutathione peroxidase (GPX) were determined. Recovered viral nucleic acids were amplified using the conventional polymerase chain reaction (SENV DNA) or the real-time polymerase chain reaction (HCV RNA) techniques. Only 10% of healthy donors had evidence of SENV infection. Among patients with thalassemia, 80% and 77% of patients with and without concurrent HCV infections, respectively, had SENV infections. DNA sequencing analyses were performed on blood samples obtained from 29 patients. Patients with thalassemia, particularly those with SENV infections, had higher levels of several enzymatic liver function markers and total serum bilirubin (P < 0.05) than did healthy blood donors. Among the examined liver function markers, only gamma-glutamyl transferase demonstrated significantly higher levels in HCV-negative patients infected with SENV-H than in those infected with SENV-D (P = 0.01). There were significantly lower vitamin C, vitamin E, and glutathione peroxidase levels in patients than in healthy donors (P < 0.05), but only glutathione peroxidase levels were significantly lower in HCV-negative thalassemia patients infected with SENV than in those without SENV infections (P = 0.04). The SENV-H genotype sequences were similar to the global standard genes in GenBank. These results increase our understanding of the nature of the SENV-H genotype and the differential role of SENV-H infections, compared to SENV-D infections, in patients with thalassemia, in Iraq. Author summary In patients with β-thalassemia, regular blood transfusions increase patient survival but increase the risk of acquiring blood-borne viral infections, especially viral hepatitis. The SEN virus (SENV) is associated with non-A-E hepatitis but its exact role in the pathogenesis of liver disease remains unknown. This study investigated the frequency of SENV infections among Iraqi patients with thalassemia, with and without hepatitis C infections. The study revealed that the prevalence of SENV infections is significantly higher in patients with β-thalassemia, regardless of their hepatitis C infection status, than in a healthy population of blood donors. The two most common genotypes of the virus (D and H) have generally similar physiological impacts as both increase the levels of markers of hepatic dysfunction in thalassemia patients. However, SENV-H infections were associated with significantly higher levels of gamma-glutamyl transferase in HCV-negative patients with thalassemia, potentially predicting hepatocellular carcinoma development. Although thalassemia patients demonstrated significantly lower levels of the antioxidants vitamins C and E, compared with healthy donors, only the levels of glutathione peroxidase (another antioxidant) were significantly lower in SENV-infected patients than in non-SENV-infected patients. This study aids our understanding of the differential effects of SENV-D and SENV-H infections in β-thalassemia patients.