Increased systemic sST2 in patients with end stage renal disease contributes to milder liver damage during HCV infection

Abstract

Introduction: Hepatitis C Virus (HCV) is the leading cause of chronic liver disease and is a serious global health problem. Hepatitis C infection is highly prevalent in patients with end stage renal disease (ESRD), due to frequent exposure to blood and blood products, nosocomial transmission of HCV, and prolong hemodialysis duration. The aim of the study was to evaluate the influence of IL-33/ST2 signaling pathway on severity of the liver disease in ESRD HCV+ patients.
 Methodology: Blood samples from patients with end stage renal disease (ESRD) and hepatitis C infection (HCV), 20 patients with HCV infection, 20 patients with ESRD and 20 healthy control donor patients were taken for the examination of biochemical parameters, for the determination of the serum cytokine concentration, and for the molecular diagnostics of HCV.
 Results: Systemic sST2 positively correlated with serum level of urea and creatinine, respectively. Serum sST2 was significantly increased in ESRD HCV+ patients in comparison to HCV+ group. sST2/IL-1, sST2/IL-4 and sST2/IL-23 ratios were significantly increased in serum of ESRD HCV+ patients in comparison to HCV+ patients. Significantly higher systemic level of sST2 and sST2/IL-1 and sST2/IL-4 ratios were measured in ESRD patients compared to non-ESRD patients.
 Conclusion: These results suggested that elevated level sST2, as the consequence of renal failure, causes less destruction of liver in HCV infection.

Interleukin-33/ Suppression of Tumorigenicity 2 in Renal Fibrosis: Emerging Roles in Prognosis and Treatment

“…In fact, in a cohort study of critically ill patients, the ones with elevated sST2 expression had the worst prognosis (Dieplinger et al, 2016). However, some studies indicate that sST2 is a better indicator of risk for end-stage dialysis than IL-33 in patients with kidney disease (Bao et al, 2012;de Boer et al, 2015;Tuegel et al, 2018;Lukic et al, 2020;Yan et al, 2020). For instance, Bao et al (2012) did not observe any difference in the serum IL-33 concentrations of patients with CKD and that of healthy individuals.…”

HCV Infection and Chronic Renal Disease

“…Soluble form of ST2 is a decoy receptor for IL-33, which blocks IL-33/ST2 signaling and inhibit inflammation, so ST2 can be considered as an immunosuppresive molecule targeting innate and aquired anti HCV immune response. (64). This implicate less liver damage and its protective role of sST2 in ESRD HCV+ patients (64).…”

“…They found positive correlation between serum level of sST2 and urea and creatinine, and no effect of viral activity on systemic value of sST2 (64). For the first time it was noticed increased level of sST2, significantly increased sST2/IL-1, sST2/IL-4 and sST2/IL-23 ratio in ESRD HCV+ patients in comparison with HCV+ patients (64). Soluble form of ST2 is a decoy receptor for IL-33, which blocks IL-33/ST2 signaling and inhibit inflammation, so ST2 can be considered as an immunosuppresive molecule targeting innate and aquired anti HCV immune response.…”

“…Gal-3 and IL-6 protect the liver from virus destruction, subsequently decreasing systemic level of AST and ALT and also stimulates liver regeneration (61). In one study was tested IL-33/sST2 pathway in ESRD HCV+ patients and HCV+ patients without ESRD (64). They found positive correlation between serum level of sST2 and urea and creatinine, and no effect of viral activity on systemic value of sST2 (64).…”

“…In one study was tested IL-33/sST2 pathway in ESRD HCV+ patients and HCV+ patients without ESRD (64). They found positive correlation between serum level of sST2 and urea and creatinine, and no effect of viral activity on systemic value of sST2 (64). For the first time it was noticed increased level of sST2, significantly increased sST2/IL-1, sST2/IL-4 and sST2/IL-23 ratio in ESRD HCV+ patients in comparison with HCV+ patients (64).…”