Value of toll-like receptor 3 (TLR3) in chronic kidney disease patients with hepatitis C virus infection

Background Hepatitis C virus (HCV) infection is a severe public health problem with a worldwide predominance of 3%. An estimated 5–20% of infected patients develop cirrhosis annually, and 1–4% of them develop hepatocellular carcinoma. In Egypt, the prevalence of HCV antibody and HCV RNA are 10.0 and 7.0%, respectively, in the 15–59 years age group. In children of 1–14 years old, the prevalence of HCV antibody and HCV RNA are 0.4 and 0.2%, respectively. HCV infection is a cause of chronic kidney disease (CKD) and results in a significant problem in hemodialysis (HD) patients. Toll-like receptors (TLRs) might have an essential role in the pathogenesis of renal diseases. They include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13, though the latter two are not found in humans. Recently, it is shown that the mouse and human kidney tubular epithelial cells appear to express TLR3 constitutively and upregulate its expression upon challenge with its legend. For this reason, it appears conceivable that this receptor might play an essential role in this organ in health and disease. Aim The present study was carried out to determine the value of TLR3 in CKD patients with HCV infection. Also, we aimed to study the levels of TLR3 for Child–Pugh different classes to determine its impact on the prognosis of liver disease in those patients. Patients and methods All participants were selected from the National Institute of Urology and Nephrology. Their ages ranged between 40 and 62 years. Our study included 130 individuals of which 105 patients were selected from a dialysis unit with the end-stage renal disease on regular HD three times/week for at least 1 year and 25 healthy participants as a control group. They were divided into three groups. The control group (GI) consisted of 25 clinically healthy participants matched for age and sex; GII constituted 45 HCV negative patients; and GIII had 60 HCV positive patients. GIII was subclassified into GIIIA, GIIIB, and GIIIC, each of which consisted of 20 patients according to the Child–Pugh scoring. All patients and control samples were subjected to the following tests: Antibody screening for HCV using the ELISA technique and quantitative HCV RNA by PCR. Detection of TLR3 was done using the ELISA technique. Other parameters such as Complete Blood Picture (CBC), Prothrombin Time (PT) (INR), urea, creatinine, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), total bilirubin, alkaline phosphatase, albumin, cholesterol, and triglycerides levels were also estimated. Results The percentage of HCV-positive cases among a studied group of patients on HD was 57.2%, and the percentage of negative cases was 42.8%. There was no significant difference between GI, GII, and GIII as regards age and duration of dialysis. There was a highly significant difference between GIII as regards TLR3, INR, urea, total bilirubin, albumin, and triglycerides compared with GI and GII. There was a highly significant positive correlation of TRL3 with creatinine and PCR RNA and a significant negative correlation with albumin and cholesterol. We also found that there was a highly significant difference between GIIIC as regards INR, total bilirubin, and albumin compared with GIIIA and GIIIB. TLR3 showed no significant difference between GIIIA, GIIIB, and GIIIC. Conclusion TLR3 may have a role in the pathogenesis of HCV infection-related CKD and can be used as a new marker for the development of HCV related end-stage renal disease.