Role of Programmed Cell Death-1 and Programmed Cell Death Ligand-1 immune checkpoint biomarkers among chronic Hepatitis C virus patients under Hemodialysis
Background: Hepatitis C virus (HCV) infection is one of the most common infections associated with chronic kidney disease (CKD) patients undergoing hemodialysis (HD) in Iraq.
Aim of the study: To determine the prognostic factor value of Programmed Cell Death-1 (PD-1) and Programmed Cell Death Ligand-1 (PD-L1) immune checkpoint biomarkers among CKD patients with HCV infection under HD.
Methodology: ELISA technique was used for the measurement of the above-mentioned biomarkers in the serum of 90 Iraqi patients. The participants were divided into three groups; Group I included 30 patients infected with HCV without antiviral treatment, group II included 30 patients infected with HCV with recent/previous antiviral treatment, and Group III included 30 patients without viral infection (control group).
Results: Serum levels of the measured biomarkers were elevated among all the participants, and highly statistically significant differences were found between patients with no treatment. The area under the curve (AUC) of PD-1 was 99% and for PD-L1 was 96%.
Conclusions: The PD-1 and PD-L1 immune checkpoint biomarkers have excellent prognostic factor value as predictors for patients with CKD on HD infected with HCV.
Jalota, A.; Brian, K.L.; Beje, T. and Edgar, V.L. Hepatitis C and treatment in patients with CKD. Disease-A-Month. 2021. Vol. 67. P. 101017.
Chan, S.T. and Ou, J.H.J. HCV-induced autophagy and host innate immune response. Viruses. 2017. Vol. 9. P. 224.
Salman, H.S; Ibrahim, B.M. and Al-Khafagi, A.F. Serum levels of ICAM-1, N-Terminal pro-BNP and TnI among HD patients with HCV. J. Cardio. Dis. Res. 2021. Vol. 12, № 05. P. 696-700.
Fadi, S.; Markos K.; Katrina B.; Douglas S.; Eleftherios M., et al. Efficacy and safety of sofosbuvir in the treatment of hep C among patients on HD: A systematic review and meta- analysis. Scientific Reports. 2020. Vol. 10. P. 1-10.
Ledezma-Morales, M. and Amariles, P. Treatment of CHC in elderly patients with CKD: A structured review. Revista Colombiana de Gastroenterologia. 2018. Vol. 33. P. 269-84.
Strohbehn, I.A.; Rituvanthikaa, S.; Meghan, L. and Meghan E.S. Curative therapies for HCV infection in patients with kidney disease. Kidney. 2021. P. 360.
Malnick, S.D.H.; Abdullah, A. and Neuman, M.G. Checkpoint Inhibitors and Hepatotoxicity. Biomedicines. 2021. Vol. 9. P. 101.
Alkrekshi, A. and Tamaskar, I. Safety of immune checkpoint inhibitors in patients with cancer and HCV infection. Oncologist. 2021. Vol. 26. P. e827- e830.
Gu, D.; Xiang, A.; Yu, Y.; Zhuo, C. and Xiang, X. Soluble immune checkpoints in cancer: Production, function and biological significance. J. Immuno. Cancer. 2018. Vol. 6. P. 1-14.
Carlino, M.S.; Larkin, J. and Long, G.V. Immune checkpoint inhibitors in melanoma. Lancet. 2021. Vol. 398. P. 1002-1014.
McBride, M.A.; Patil, T.K.; Bohannon, J.K.; Hernandez, A.; Sherwood, E.R., et al. Immune checkpoints: Novel therapeutic targets to attenuate sepsis-induced immunosuppression. Frontiers in Immunology. 2021. Vol. 11, Article 624272. P. 1-14.
Cai, H.; Ge, L.; Jianfeng, Z.; Kai, Z.; Haitao, X., et al. Immune checkpoints in viral infections. Viruses. 2020. Vol. 12. P. 1051.
Cosimo, S.D.; Malfettone, A.; Perez-Garcia, J.M.; Llombart-Cussac, A.; Miceli, R., et al. Immune checkpoint inhibitors: A physiology-driven approach to the treatment of coronavirus disease. European J. Cancer. 2019. Vol. 135. P. 62-65.
Manns, M.P.; Buti, M.; Gane, E.; Pawlotsky, J-M.; Razavi, H., et al. HCV infection. Nature Review Disease Primers. 2017. Vol. 3, № 17006. P. 1-19.
Baden, R.; Jurgen, K.R. and Butiz, M. Natural history and management of Hepatitis C: Does sex play a role? J. Infect. Dis. 2014. Vol. 209, № 3. P. S81-S85.
Niccoli, T. and Partridge, L. Ageing as a risk factor for disease. Current Biology. 2012. Vol. 22, № 17. P. 741-752.
Franceschi, C.; Garagnani, P.; Morsiani, C.; Conte, M.; Santoro, A., et al. The continuum of aging and age-related diseases: Common mechanisms but different rates. Frontiers in Medicine. 2018. Vol. 5, № 61. P. 1-23.
Stroffolini, T.; Rapicetta, M. and Stefano, R.D. HCV clearance and gender. Gut. 2007. Vol. 56, № 6. P. 884-896.
Bakr, I.; Rekacewicz, C.; El Hosseiny, M. et al. Higher clearance of HCV infection in females compared with males. Gut. 2006. Vol. 55. P. 1183-1187.
Santoro, D.; Benedetto, F.; Mondello, P.; Pipito, N.; Barilla, D., et al. Vascular access for HD: Current perspectives. Int. J. Nephrol. Renovascul. Dis. 2014. Vol. 7. P. 281-294.
Dember, L.M.; Imrey, P.B. and Beck, G.J. 2014. HD fistula maturation study group. Objectives and design of the HD fistula maturation study. Am. J. Kidney Dis. 2014. Vol. 63, № 1. P. 104-112.
National Kidney Foundation (NKF). 2015. HD access. National Kidney Foundation Inc., NY, USA. Available from: https://www.kidney.org/atoz/content/hemoaccess. Last accessed: 01.07.22
Drazilova, S.; Gazda, J.; Janicko, M. and Jarcuska, P. CHC association with DM and cardiovascular risk in the Era of DAA therapy: Can. J. Gastroenterol. Hepatol. 2018. Article № 6150861.
Bucharles, S.G.; Wallbach, K.K.; Morase, T.P. and Pecoits-Filho, R. Hypertension in patients on HD: Diagnosis, mechanisms, and management. Brazilian J. Nephrology. 2018. Vol. 41. P. 400-411.
Hussain, S.S. and Azzam, H. Risk factors of CKD among patients attending Ibn Sina teaching hospital in Mosul city. Iraqi J. Medical Sciences. 2019. Vol. 17, № 1. P. 24-31.
Terada, K.; Sumi, Y.; Aratani, S.; Hirama, A.; Kashiwagi, T. et al. Plasma erythropoietin level and heart failure in patients undergoing peritoneal dialysis: A cross-sectional study. Renal Replacement Therapy. 2021. Vol. 7, № 3. P. 1-8.
Fabrizi, F.; Martin, P.; Dixit, V. and Messa, P. HCV infection and kidney disease: A meta-analysis. Clin. J. Am. Soc. Nephrol. 2012. Vol. 7. P. 549-557.
Center for Disease Control and Prevention (CDC). 2018. Healthcare-associated Hepatitis B and C outbreaks reported to the CDC 2017. Atlanta, CDC. Available from: https://www.cdc.gov/hepatitis/outbreaks/healthcarehepoutbreaktable.htm Last accessed 03.07.22
Bernieh, B. 2015. Viral hepatitis in HD: An update. J. Trans. Int. Med. Vol. 3. P. 93-105.
Constancio, N.S.; Ferraz, M.L.G.; Martins, C.T.B.; Kraychete, A.C.; Bitencourt, P.L., et al. Hepatitis C in HD units: Diagnosis and therapeutic approach. Braz. J. Nephrol. 2019. Vol. 41, № 4. P. 539-549.
Malnick, S.D.; Abdullah, A. and Neuman, M.G. Checkpoint Inhibitors and Hepatotoxicity. Biomedicines. 2021. Vol. 9. P. 101.
Cheun, H.; Kim, M.; Lee, H.; Oh, K.H. and Keam, B. Safety and efficacy of immune checkpoint inhibitors for ESRD patients undergoing dialysis: A retrospective case series and literature review. Investigational New Drugs. 2018. Available at https://doi.org/10.1007/s10637-018-0673-y. Last accessed 03.07.22
Reddy, H.G.; Schneider, B.J. and Tai, A.W. Immune checkpoint inhibitor-associated colits and hepatitis. Clin. Trans. Gastroenterol. 2018. Vol. 9. P. 180.
Hashimoto, M.; Kamphorst, A.O.; Im, S.J.; Kissick, H.T.; Pillai, R.N., et al. CD8 T-cell exhaustion in chronic infection and cancer: Opportunities for interventions. Ann. Rev. Med. 2018. Vol. 69. P. 301-318.
Simon, S. and Labarriere, N. PD-1 expression on tumor-specific T-cells: Friend or foe for immunotherapy? OncoImmunology. 2017. Vol. 7.
Andrews, L.P.; Yano, H. and Vignali, D.A.A. Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: Breakthroughs or backups. Nat. Immunol. 2019. Vol. 20. P. 1425-1434.
Barrett, M.T.; Anderson, K.S.; Lenkiewicz, E.; Andreozzi, M.; Cunliffe, H.E., et al. Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer. Oncotarget. 2015. Vol. 6. P. 26483-26493.
Zong, Z.; Zou, J.; Mao, R.; Ma, C.; Li, N., et al. M1 macrophages induce PD-L1 expression in HCC cells through IL-1β signaling. Front. Immunol. 2019. Vol. 10. P. 1643.
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