Serum IL-12p70 and TLR 7 gene expression in Egyptian patients infected with HCV and treated with Sofosbuvir, Ribavirin and/or Pegylated interferon
Paper Details
Serum IL-12p70 and TLR 7 gene expression in Egyptian patients infected with HCV and treated with Sofosbuvir, Ribavirin and/or Pegylated interferon
Abstract
Chronic hepatitis C virus infection is one of the most important health problems in Egypt. The purpose of this study was to assess the efficacy, and tolerability of two therapeutic modalities, dual (Sofosbuvir+ribavirin)and triple (sofosbuvir + ribavirin + peg-interferon), in treating Egyptian patients infected with HCV genotype-4. In addition, we determined serum IL-12p70 and TLR7 gene expression in patients infected with HCV with and without treatment, compared to the normal volunteers. No significant changes in serum creatinine and fasting blood glucose concentrations were reported at the end of the treatment with dual and triple therapy and after 3 months of follow up. Pateints infected with HCV showed a non significant change in the relative quantitation of TLR7 gene expression, and a significant elevation in serum IL-12p70 concentration (161.73%, p<0.0001), compared to the volunteers group (II). In dual and triple therapy groups (III &IV), there was a significant elevation in the relative quantitation of TLR7 gene expression (250.53 and 506.32%, respectively, p<0.0001), compared with HCV group, but these elevations returned to the normal level after 3-months of follow up period. On the other hand, the concentration of serum IL-12p70 was significantly reduced in all treated groups, compared to both healthy volunteers and HCV groups , except group III (SOF+RBV) showed a non significant change compared to healthy volunteers. The treatment modalities, either with Sofosbuvir plus ribavirin or Sofosbuvir plus ribavirin and pegylated Interferon is highly effective in our cohort of Egyptian patients infected with HCV genotype-4. Further investigations should be done to increase the time after the end of treatment modalities to ensure complete remission of HCV infection.
Abdel-Razek W, Waked I. 2015. Optimal therapy in genotype 4 chronic hepatitis C: finally cured? Liver international: official journal of the International Association for the Study of the Liver 35, 27–34. http://dx.doi.org/10.1111/liv.12724
Afify M, Hamza AH, Alomari RA. 2017. Correlation between Serum Cytokines, Interferons, and Liver Functions in Hepatitis C Virus Patients. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 37, 32-38. http://dx.doi.org/10.1089/jir.2016.0044.
Alhetheel A, Albarrag A, Shakoor Z, Alswat K, Abdo A, Al-Hamoudi W, Alomar S. 2017. Increased Spontaneous Programmed Cell Death Is Associated with Impaired Cytokine Secretion in Peripheral Blood Mononuclear Cells from Hepatitis C Virus-Positive Patients. Viral immunology 30, 283-287. http://dx.doi.org/10.1089/vim.2016.0166.
Bader El Din NG, Farouk S, El-Shenawy R, Ibrahim MK, Dawood RM, Elhady MM, Salem AM, Zayed N, Khairy A, El Awady MK. 2016. Tumor necrosis factor-α-G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients. World Journal of Gastroenterology 22, 7767-77. http://dx.doi.org/10.3748/wjg.v22.i34.7767.
Barth H. 2015. Hepatitis C virus: Is it time to say goodbye yet? Perspectives and challenges for the next decade. World journal of Hepatology 7, 725–737. http://dx.doi.org/10.4254/wjh.v7.i5.725.
Blasius AL, Beutler B. 2010.Intracellular toll-like receptors. Immunity 32, 305–15. http://dx.doi.org/10.1016/j.immuni.2010.03.012.
Boghdadi Gand Seleem WM.2014. Differential expression of Toll-like receptors 7 & 8 mRNA in monocytes of patients with chronic hepatitis C infection: correlation with interferon and ribavirin treatment. The Egyptian Journal of immunology 21, 67-75.
Borgia G, Reynaud L, Gentile 2003.Pernicious anemia during IFN-alpha treatment for chronic hepatitis C. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 23, 1-2. http://dx.doi.org/10.1089/10799900360520405.
Capone F, Costantini S, Guerriero E, Calemma R, Napolitano M, Scala S, Izzo F, Castello G. 2010. Serum cytokine levels in patients with hepatocellular carcinoma. European cytokine network 21, 99–104. http://dx.doi.org/10.1684/ecn.2010.0192.
Chang S, Kodys K, Szabo G. 2010. Impaired expression and function of toll-likereceptor 7 in hepatitis C virus infection in human hepatoma cells. Hepatology: official journal of the American Association for the Study of Liver Diseases 51, 35–42. http://dx.doi.org/10.1002/hep.23256.
Cholongitas E, Papatheodoridis GV. 2014. Sofosbuvir: a novel oral agent for chronic hepatitis C. Annals of gastroenterology 27, 331-337.
Coppola N, Pisapia R, Tonziello G. 2008. Virological pattern in plasma, peripheral blood mononuclear cells and liver tissue and clinical outcome in chronic hepatitis B and C virusco-infection. Antiviral therapy 13, 307-18.
Coppola N, Zampino R, Bellini G. 2014. Association between a polymorphism in cannabinoid receptor 2 and severe necroinflammation in patients with chronic hepatitis C. Clinical gastroenterology and hepatology: The Official Clinical Practice Journal of The American Gastroenterological Association. 12, 334-40. http://dx.doi.org/10.1016/j.cgh.2013.05.008.
Del Vecchio M, Bajetta E, Canova S, Lotze MT, Wesa A, Parmiani G, Anichini A. 2007. Interleukin-12: biological properties and clinical application. Clinical cancer research: an official journal of the American Association for Cancer Research1 3, 4677-85. http://dx.doi.org/10.1158/1078-0432.CCR-07-0776
Dolganiuc A, Garcia C, Kodys K, Szabo G. 2006. Distinct Toll-like receptor expression in monocytes and T cells in chronic HCV infection. World journal of gastroenterology 12, 1198–204.
El Raziky M, Fathalah WF, El-Akel WA, Salama A, Esmat G, Mabrouk M, Salama RM, Khatab HM. 2013. The Effect of Peginterferon Alpha-2a vs. Peginterferon Alpha-2b in Treatment of Naive Chronic HCV Genotype-4 Patients: A Single Centre Egyptian Study. Hepatitis monthly 13, e10069. http://dx.doi.org/10.5812/hepatmon.
El-Emshaty HM, Nasif WA, Mohamed IE. 2015. Serum Cytokine of IL-10 and IL-12 in Chronic Liver Disease: The Immune and Inflammatory Response. Disease Markers7 pages. http://dx.doi.org/10.1155/2015/707254.
Elsharkawy A, Fouad R, El Akel W, El Raziky M, Hassany M, Shiha G, Said M, Motawea I, El Demerdash T, Seif S, Gaballah A, El Shazly Y, Makhlouf MA, Waked I, Abdelaziz AO, Yosry A, El Serafy M, Thursz M, Doss W, Esmat G. 2017.Sofosbuvir-based treatment regimens: real life results of 14 409 chronic HCV genotype 4 patients in Egypt. Alimentary pharmacology and therapeutics 45, 681-687. http://dx.doi.org/10.1111/apt.13923.
European Association for study of liver. 2015. EASL Recommendations of treatment of hepatitis C 2015. International journal of hepatology 36, 199-236. http://dx.doi.org/10.1016/j.jhep.2015.03.025.
Funk E, Kottilil S, Gilliam B, Talwani R. 2014. Tickling the TLR7 to cure viral hepatitis. Journal of translational medicine 12, 129. http://dx.doi.org/10.1186/1479-5876-12-129.
García-Suárez J, Burgaleta C, Hernanz N, Albarran F, Tobaruela P, Alvarez-Mon M. 2000. HCV-associated thrombocytopenia: clinical characteristics and platelet response after recombinant alpha2b-interferon therapy. British journal of haematology 110, 98-103. http://dx.doi.org/10.1046/j.1365-2141.2000.02132.x.
Gigi E, Raptopoulou-Gigi M, Kalogeridis A, Masiou S, Orphanou E, Vrettou E, Lalla TH, Sinakos E, Tsapas V. 2008. Cytokine mRNA expression in hepatitis C virus infection: TH1 predominance in patients with chronic hepatitis C and TH1-TH2 cytokine profile in subjects with self-limited disease. Journal of viral hepatitis 15, 145-54. http://dx.doi.org/10.1111/j.1365-2893.2007.00908.x.
Gower E, Estes CC, Hindman S, Razavi-Shearer K, Razavi H. 2014.Global epidemiology and genotype distribution of the hepatitis C virus.Journal of hepatology 61, S45–57. http://dx.doi.org/10.1016/j.jhep.2014.07.027.
Guerra J, Garenne M, Mohamed MK, Fontanet A. 2012.HCV burden of infection in Egypt: results from a nationwide survey. Journal of viral hepatitis 19, 560–7. http://dx.doi.org/10.1111/j.1365-2893.2011.01576.x.
Herbst Jr, Reddy K. 2013. Sofosbuvir a Nucleotide Polymerase Inhibitor for the Treatment of Chronic Hepatitis C Virus Infection. Expert Journal opinion on investigational drugs 22, 527-536.
HiroishiK ,Lto T, Imawari M .2008. Immune responses in hepatitis infection and mechanisms of hepatitis C virus persistence. Journal of Gastroenterology and Hepatology 23, 1473–1482. http://dx.doi.org/10.1111/j.1440-1746.2008.05475.x.
Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdorfer B, Giese T. 2002.Quantitative expression of toll-like receptors 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to Cp Goligodeoxynucleotides. The Journal of immunology: official journal of the American Association of Immunologists 168, 4531–7. http://dx.doi.org/10.4049/jimmunol.168.9.4531.
Hyers TM, Agnelli G, Hull RD, Morris TA, Samama M, Tapson V, Weg JG. 2001. Antithrombotic therapy for venous thromboembolic disease. Chest Journal official publication of the American collage of chest physicians 119, 176-193.
Ibrahim MK, Salum GM, Bader El Din NG, Dawood RM, Barakat A, Khairy A, El Awady MK. 2016.Transcriptional Dysregulation of Upstream Signaling of IFN Pathway in Chronic HCV Type 4 Induced Liver Fibrosis. Plo Sone 11, e0154512. http://dx.doi.org/10.1371/journal.pone.0154512.
Imran M, Waheed Y, Manzoor S, Bilal M, Ashraf W, Ali M. 2012. Interaction of Hepatitis C virus proteins with pattern recognition receptors. Virology Journal 9, 126. http://dx.doi.org/10.1186/1743-422X-9-126.
Kondo Y, Ueno Y, Kakazu E. 2011.Lymphotropic HCV strain can infect human primary naïve CD4(+) cells and affect their proliferation and IFN gamma secretion activity. Journal of Gastroenterology 46, 232-41.
Kuter DJ, Begley CG. 2002. Recombinant human Thrombopoietin: basic biology and evaluation of clinical studies. Blood 100, 3457– 3469. https://dx.doi.org/10.1182/blood.V100.10.3457
Lavanchy D. 2009. The global burden of hepatitis C. Liver international: official journal of the International Association for the Study of the Liver 29, 74–81. http://dx.doi.10.1111/j.1478-3231.2008.01934.x
Leticia OI, Andrew A, Obeagu EI, Ugochukwu A. 2014. The Effect of Viral Hepatitis ON APTT, PT, TT, Fibrinogen and Platelet among Blood Donors at FMC.IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) 13, 57-63. http://dx.doi.org/10.9790/0853-13855763
Mele D, Mantovani S, Oliviero B, Grossi G, Ludovisi S, Mondelli MU, Varchetta S. 2016. Hepatitis C virus inhibits CD4 T cell function via binding to Toll-like receptor 7.Antiviral Research 137, 108-111. http://dx.doi.org/10.1016/j.antiviral.2016.11.013.
Miller MH, Agarwal K, Austin A, Brown A , Barclay ST, Dundas P, Dusheiko GM, Foster GR, FOX R, Hayes PC, Leen C, Millson C, Ryder DS, Tait J, Ustianowski A. 2014.Review article: 2014 UK consensus guidelines – hepatitis C management and direct-acting anti-viral therapy. Alimentary pharmacology & therapeutics 39, 1363-75. http://dx.doi.org/10.1111/apt.12764.
Mohammed KI, Adel LA, Ali-Eldin FA, Eladawy S. 2013.Expression of Toll like receptors 3 & 7 in peripheral blood from patients with chronic hepatitis C virus infection and their correlation with interferon-alpha. The Egyptian Journal of immunology 20, 13–22.
Moreno C, Hezode C, Marcellin P, Bourgeois S, Francque S, Samuel D, Zoulim F, Grange JD, Shukla U, Lenz O, Ouwerkerk-Mahadevan S, Fevery B, Peeters M, Beumont M, Jessner W.2015. Efficacy and safety of simeprevir with Peg IFN/ribavirin in naive or experienced patients infected with chronic HCV genotype 4. Journal of Hepatology 62, 1047–55. http://dx.doi.org/10.1016/j.jhep.2014.12.031.
Morsy KH, Zaghloul A, Mahmoud M. 2016. Can eicosapentaenoic acid maintain the original ribavirin dose or affect the response during the treatment course of chronic hepatitis C virus (HCV) patients?. The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 27, 55-61. http://dx.doi.org/10.5152/tjg.2015.150280.
Motavaf M, Noorbakhsh F, Alavian SM, Sharifi Z. 2014.Distinct Toll-like Receptor 3 and 7 Expression in Peripheral Blood Mononuclear Cells From Patients with Chronic Hepatitis C Infection. International Monthly Journal in the field of hepatology 14, e16421. http://dx.doi.org/10.5812/hepatmon.16421.
Pawlotsky JM. 2014. New hepatitis C therapies: The toolbox, strategies, and challenges. Gastroenterology 146, 1176–1192. http://dx.doi.org/10.1053/j.gastro.2014.03.003
Perperas A, Karagiannakis D, Anagnostopoulos G, Tsirogiannis A, Panagiotakos D, Papadopoulos S, Tsagkaris M, Papasteriades C, Manolakopoulos S. 2013. Pretreatment serum interleukin-12 levels in predicting sustained virological response among hepatitis C patients following Pegylated Interferon-α2β plus Ribavirin treatment. Annals of Gastroenterology 26, 249-254.
Rajan S, Liebman HA. 2001. Treatment of hepatitis C related thrombocytopenia with interferon alpha. American journal of hematology 68, 202-209. http://dx.doi.org/10.1002/ajh.1180.
Rehermann B. 2009.Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. Journal of Clinical Investigation 119, 1745–1754. http://dx.doi.org/10.1172/JCI39133.
Revie D, Salahuddin SZ. 2011.Human cell types important for hepatitis C virus replication in vivo and in vitro: old assertions and current evidence. Virology Journal 8, 346. http://dx.doi.org/10.1186/1743-422X-8-346.
Tarantino G, Di Cristina A, Pipitone R, Almasio PL, Di Vita G, Craxi A, Grimaudo S. 2013. In vivo liver expression of TLR2, TLR3 and TLR7 in chronic hepatitis C. Journal of biological regulators and homeostatic agents 27, 233-9.
Taylor MW, Tsukahara T, Brodsky L, Schaley J, Sanda C, Stephens MJ, McClintick JN, Edenberg HJ, Li L, Tavis JE, Howell C, Belle SH. 2007.Changes in gene expression during peginterferon and Ribavirin therapy of chronic hepatitis C distinguish responders from non responders to antiviral therapy. Journal of virology 81, 3391-3401.
Thomas A, Laxton C, Rodman J, Myangar N, Horscroft N, Parkinson T. 2007.Investigating Toll-like receptor agonists for potential to treat hepatitis C virus infection. Antimicrobial agents and chemotherapy 51, 2969–78.
Waked I, Doss W, El-Sayed MH. 2014. The current and future disease burden of chronic hepatitis C virus infection in Egypt. Arab journal of gastroenterology: the official publication of the Pan-Arab Association of Gastroenterology 15, 45–52. http://dx.doi.org/10.1016/j.ajg.2014.04.003.
Watford WT, Moriguchi M, Morinobu A, O’Shea JJ. 2003. The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine & growth factor reviews 14, 361–8. http://dx.doi.org/10.1016/S1359-6101(03)00043-1
Youssef S, Abd El-Aal M A, Saad A, Omran H M, El Zanaty T, Seif MS. 2013. Impact of IL12B Gene rs 3212227 Polymorphism on Fibrosis, Liver Inflammation, and Response to Treatment in Genotype 4 Egyptian Hepatitis C Patients. Disease Markers 35, 431–43. http://dx.doi.org/10.1155/2013/627589.
Zhang Y , GuoY, LiB, Sun S. 2009.Hepatitis C virus single-stranded RNA induces innate immunity via Toll-like receptor 7. Journal of Hepatology 51, 29-38. http://dx.doi.org/10.1016/j.jhep.2009.03.012.
Hala M. Aldesouki, Hanan M. Zidan, Eman M. Elashry (2017), Serum IL-12p70 and TLR 7 gene expression in Egyptian patients infected with HCV and treated with Sofosbuvir, Ribavirin and/or Pegylated interferon; IJB, V10, N6, June, P179-194
https://innspub.net/serum-il-12p70-and-tlr-7-gene-expression-in-egyptian-patients-infected-with-hcv-and-treated-with-sofosbuvir-ribavirin-and-or-pegylated-interferon/
Copyright © 2017
By Authors and International
Network for Natural Sciences
(INNSPUB) https://innspub.net
This article is published under the terms of the
Creative Commons Attribution License 4.0