Increased incidence of cytomegalovirus coinfection in HCV-infected patients with late liver fibrosis is associated with dysregulation of JAK-STAT pathway

Abstract

Herein, we examined the association between cytomegalovirus (CMV) coinfection and the progression of liver fibrosis in hepatitis C virus (HCV) infection, and investigated the effect of CMV coinfection on JAK-STAT pathway. CMV DNAemia was detected by PCR in DNA from controls (n = 120), and HCV patients with early (F0-F1, n = 131) and late (F2-F4, n = 179) liver fibrosis. By quantitative real time PCR (qRT-PCR), we examined the profile of 8 JAK-STAT transcripts in PBMCs RNA from 90 HCV patients (39 CMV positive and 51 CMV negative), 4 CMV mono-infected patients, and 15 controls. Our results demonstrated higher incidence of CMV in F2-F4 group than in control (OR 5.479, 95% CI 3.033–9.895, p < 0.0001) or F0-F1 groups (OR 2, 95% CI 1.238–3.181, p = 0.005). qRT-PCR showed downregulation of STAT2 (p = 0.006) and IRF7 (p = 0.02) in CMV positive group compared to CMV negative one. The downregulation of STAT2 and IRF7 was mainly in CMV positive patients with late fibrosis compared to CMV negative patients (p = 0.0007 for IRF7 and p = 0.01 for STAT2). Our results are the first to report that CMV coinfection is a possible risk factor for the progression of HCV-induced liver fibrosis, and thereby CMV screening and treatment are important for HCV patients.

Serological and Immunohistochemical Prevalence of Human Cytomegalovirus Co-infection among Hepatitis C Virus Patients Admitted to Kafer El Shiekh Liver and Heart Institute, Egypt

“…Among one hundred HCV agreement percentage between the results of ELISA, and those of IHC was 76%. 45.24%, 0.00% than males, 50.00%, and 6.67% using ELISA and IHC, respectively. Although, higher prevalence was recorded in younger patients and urban area residents compared to older patients and rural area residents, no significant difference was detected in the patients was province 8.51% was detected in the (Fig.…”

“…In the current study, liver cirrhosis at patient with concomitant CMV IgG and chronic HCV infections showed a high percentage compared to those patients with chronic HCV monoinfection. Previous study demonstrated an intimate relationship between CMV and the progression of liver injuries such as steatosis and fibrosis in HCV patients [45]. Moreover, several reports illustrated augmented severity of hepatitis activity index and fibrosis status during CMV/ HCV co-infection in patients undergoing liver transplantation [46][47][48].…”

Latent Cytomegalovirus Reactivation in Patients With Liver Failure: A 10-Year Retrospective Case-Control Study, 2011-2020

“…However, the risk factors and outcomes of CMV reactivation in liver failure patients remain to be extensively investigated. Previous study indicated that CMV coinfection was a possible risk factor for the progression of liver fibrosis ( Ibrahim et al., 2017 ). A cytokine storm may be induced, leading to the development of sepsis in patients with liver failure, who are susceptible for opportunistic pathogens such as CMV ( Sarin and Choudhury, 2018 ).…”

The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system

“…Caspase-1, caspase-4, and capase-12 are inflammatory caspases, whereas caspase-3 and caspase-7 comprise apoptotic executioners 22–24 . The Janus kinase (JAK) tyrosine kinase family and JAK/STAT signal transduction pathway might function during fibrogenesis in various organs including the kidney, heart, lung, liver, and bone marrow by promoting oxidative stress-induced apoptosis 25–27 . These findings suggest that APE1 suppresses oxidative stress-induced apoptosis by inhibiting the activation of multiple caspases and JAK/STAT signaling.…”