Possible effects of human cytomegalovirus/epstein-barr virus coinfection on the liver functions of chronic hepatitis B patients
Abstract
Aim: The reactivation of Human Cytomegalovirus (HCMV) and Epstein-Barr Virus (EBV), which are the common pathogens of opportunistic infection in immunosuppressed patients, is usually asymptomatic in the immunocompetent host, but may seriously affect the prognosis of the disease with viruses like HBV, which causes chronic diseases. The purpose of this study was to determine the prevalence of HCMV/EBV infection, the risk factors of coinfection, and their effects on the liver functions of chronic HBV patients whose histological activity index are known. Method: A total of 166 patients, 142 diagnosed with chronic HBV (CHB), 20 with HBV-related cirrhosis and 4 with HBV-related hepatocellular carcinoma (HCC), were retrospectively included in this study. The HCMV/EBV DNA expression was determined from the patient serums with real-time Quantitative Polymerase Chain Reaction (RT-qPCR). Results:It was determined that 3.01% of the HBV patients, who were included in the study, were identified as HCMV, and 6.02% were EBV. The Alanine Aminotransferase (ALT) levels of the CHB patients who were coinfected with HCMV were higher than those who were not infected; and there were no differences in terms of the ALT levels between those who were coinfected with EBV and who were not. Histological activity scores of the patients who were coinfected with HCMV/EBV were higher than those without HCMV/EBV coinfection. Meanwhile, the HBV DNA loads of the patients with HCMV/EBV coinfection were lower than the patients without it. Conclusion: This study showed that HCMV/EBV coinfection may be important in immunocompromised CHB patients as well as in immunosuppressed CHB patients. Despite the low HBV DNA levels in CHB patients with HCMV/EBV coinfection, high histological activity scores show that they increase liver damage and affect prognosis poorly. For this reason, we believe that accepting and treating CHB patients as high risk groups for HCMV/EBV infection and following-up and treating them for these infections will have critical importance in changing the poor prognosis of the disease.
References
- 1. Longerich T. Hepatocellular carcinoma. Pathologe. 2020;41(5):478-487. doi: 10.1007/s00292-020-00801.
- 2. Lanini S, Ustianowski A, Pisapia R, Zumla A, Ippolito G. Viral Hepatitis: Etiology, Epidemiology, Transmission, Diagnostics, Treatment, and Prevention. Infect Dis Clin North Am. 2019;33(4):1045-1062. doi: 10.1016/j.idc.2019.08.004.
- 3. Noor A, Panwala A , Forouhar F , Wu GY. Hepatitis caused by herpes viruses: A review. J Dig Dis. 2018;19(8):446-455. doi: 10.1111/1751-2980.12640.
- 4. Polakos NK, Cornejo JC, Murray DA, et al. Kupffercell-dependent hepatitis occurs during influenza infection. Am J Pathol. 2006;168(4):1169-78. doi: 10.2353/ajpath.2006.050875.
- 5. Raghav R, Samour J. Inclusion Body Herpesvirus Hepatitis in Captive Falcons in the Middle East: A Review of Clinical and Pathologic Findings. J Avian Med Surg. 2019;1;33(1):1-6. doi: 10.1647/2018-341.
- 6.Oksuz Z, Serin MS, Serin A, Sezgin O, Gonca S. Determination of reverse transcriptase inhibitör nucleoside analogue resistance profile in pretreatment phase of patients with viral hepatitis B. Mikrobiyol Bul. 2019;53(2):156-169. doi: 10.5578/mb.67796.
- 7. Sezgin O, Altıntaş E, Üçbilek E, Tombak A. Percutaneous Liver Biopsies: Safety and Efficacy. Turkiye Klinikleri J Med Sci. 2010;30(4):1287-91. doi: 10.5336/medsci.2009-13508
- 8. Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. J Hepatol. 2003;38(4):382-6. doi: 10.1002/hep.1840010511.
- 9. Tan L, Sato N, Shiraki A, et al. Everolimus delayed and suppressed cytomegalovirus DNA synthesis, spread of the infection, and alleviated cytomegalovirus infection. Antiviral Res. 2019;162:30-38. doi: 10.1016/j.antiviral.2018.12.004.
- 10. Hwang KA, Ahn JH, Nam JH. Development andvalidation of multiplexreal-time PCR assays for rapid detection of cytomegalovirus, Epstein-Barrvirus, and polyomavirus BK in whole blood from transplant candidates. J Microbiol. 2018;56(8):593-99. doi: 10.1007/s12275-018-8273-2.
- 11. Ryan JL, Fan H, Glaser SL, Schichman SA, Raab-Traub N, Gulley ML. Epstein-Barr virüs quantitation by real-time PCR targeting multiple gene segments: a novel approach to screen for the virus in paraffin-embedded tissue and plasma. J Mol Diagn. 2004;6(4):378-85. doi: 10.1016/S1525-1578(10)60535-1.
- 12. Barcelos F, Martins C, Monteiro R, et al. Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis. Sci Rep. 2021;18;11(1):4082. doi: 10.1038/s41598-021-83550-0.
- 13. Cassaniti I, Cavagna L, Calarota SA, et al. Evaluation of EBV- and HCMV-Specific T Cell Responses in Systemic Lupus Erythematosus (SLE) Patients Using a Normalized Enzyme-Linked Immunospot (ELISPOT) Assay. J Immunol Res. doi: 10.1155/2019/4236503.
- 14. Schuch A, Zecher BF, Müller PA, et al. NK-cell responses are biased towards CD16-mediated effector functions in chronic hepatitis B virus infection. J Hepatol. 2019;70(3):351-360. doi: 10.1016/j.jhep.2018.10.006.
- 15. Hu J, Zhao H, Lou D, et al. Human cytomegalovirus and Epstein-Barr virüs infections, risk factors, and their influence on the liver function of patients with acute-on-chronic liver failure. BMC Infect Dis. 2018;18(1):577. doi: 10.1186/s12879-018-3488-8.
- 16. Lian YL, Wu WF, Shi YM, Liu QC, Tang XP. Preliminary study on relationship between different viral pathogenesis and disease prognosis in patients with severe viral hepatitis. Zhonghua Shi Yan He Lin Chuang Bing DuXueZaZhi. 1999;13(4):355-7.
- 17- Faivre M, Cottet V, Bour JB, et al. Study Group.Impact of Cytomegalovirus Infection on the Outcome of Patients With Cirrhosis: A Preliminary Study, J Clin Gastroenterol. 2019;53(3):236-241. doi: 10.1097/MCG.0000000000001039.
- 18- Varani S, Lazzarotto T, Margotti M, et al. Laboratory signs of acute or recent cytomegalovirus infection are common in cirrhosis of the liver. J MedVirol. 2000;62(1):25-8. doi: 10.1002/1096-9071(200009)62:1
- 19- Giacchino R, Navone C, Ciravegna B, Viscoli C, Ferrea G, Facco F. Livercirrhosis in childhood. Considerations on 22 cases with differentetiology. Pediatr Med Chir. 1990;12(2):147-52.
- 20. An H, Zhou XJ, Miu CM. Clinical study on there lationship between EBV infection and liver diseases infected by HBV. Zhong XI YiJie He GanBingZaZhi. 2005;15:144–5.
- 21. Gallegos-Orozco JF, Rakela-Brödner J. Hepatitis Viruses: Not Always What It Seems to Be. Rev Med Chil. 2010;138(10):1302-11.
- 22. Mellinger JL, Rossaro L, Naugler WE, et al. Epstein-Barrvirus (EBV) related acute liver failure: a case series from the US acute liver failure study group. Dig Dis Sci. 2014;59(7):1630-7. doi: 10.1007/s10620-014-3029-2.
- 23. Cavanaugh VJ, Guidotti LG, Chisari FV. Inhibition of hepatitis B virüs replication during adenovirus and cytomegalovirus infections in transgenic mice. J Virol. 1998;72(4):2630-7. doi: 10.1128/JVI.72.4.2630-2637.
- 24. Rao SC, Ashraf I, Mir F, Samiullah S, Ibdah JA, Tahan V. Dual Infection with Hepatitis B and Epstein Barr Virus Presenting with Severe Jaundice, Coagulopathy, and Hepatitis B Virus Chronicity Outcome. Am J Case Rep. 2017;18:170-172. doi: 10.12659/ajcr.901688.
- 25.Fan J, Jing M, Yang M, et al. Herpesvirus infections in hematopoietic stem cell transplant recipients sero positive for human cytomegalovirus before transplantation. Int J InfectDis. 2016;46:89-93. doi: 10.1182/blood-2005-11-012864.
- 26. Ataman S, Çolak D, Günseren F ve ark. Investigation of Cytomegalovirus Seroepidemiology in Antalya With a Population-Based Cross-Sectional Studyand Review of Related Data in Turkey. Mikrobiyol Bul. 2007;41(4):545-55.
- 27.Renner EL, Dällenbach A. Increased Liver Enzymes: What Should Be Done?. Ther Umsch. 1992;49(5):281-6.
- 28. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Clin Liver Dis (Hoboken). 2018;12(1):33-4. doi: 10.1002/hep.29800.
İnsan sitomegalovirüs/ epstein-barr virüs koenfeksiyonunun kronik hepatit b hastalarının karaciğer fonksiyonları üzerine olası etkileri
Abstract
Amaç: İmmünsüprese hastalarda fırsatçı enfeksiyonun yaygın patojenleri olan İnsan Sitomegalovirüs (HCMV) ve Epstein-Barr virüsün (EBV) immünokompetan konakçıda yeniden aktivasyonu genellikle asemptomatiktir, ancak kronik hastalığa neden olan HBV gibi virüslerle koenfeksiyonu hastalığın prognozunu kötü etkileyebilir. Bu çalışmada histolojik aktivite indeksi bilinen kronik HBV hastalarında HCMV/EBV enfeksiyon prevalansının, koenfeksiyonun risk faktörlerinin ve bunların hastaların karaciğer fonksiyonlarına olası etkilerinin belirlenmesi amaçlandı. Yöntem: Çalışmaya 142 kronik HBV (KHB), 20 HBV’ye bağlı siroz ve 4 HBV’ye bağlı hepatosellüler karsinoma (HSK) tanısı alan toplam 166 hasta retrospektif olarak dâhil edildi. HCMV/EBV DNA amplifikasyonu, gerçek zamanlı kantitatif polimeraz zincir reaksiyonu (RT-qPZR) ile hasta serumlarından belirlendi. Bulgular: Çalışmaya dâhil edilen HBV hastalarının %3.01 HCMV tespit edilirken, %6.02 EBV tespit edilmiştir. HCMV ile koenfekte KHB hastalarında alanin aminotransferaz (ALT) düzeyleri koenfeksiyonu olmayan hastalara nazaran daha yüksek bulunmuşken (p<0.05), EBV ile koenfekte hastalar ile olmayanlar arasında ALT seviyesi açısından bir fark bulunamamıştır. HCMV/EBV koenfekte hastaların histolojik aktivite skorları HCMV/EBV koenfeksiyonu olmayanlardan daha yüksek olduğu tespit edilmiştir. Aynı zamanda HCMV/EBV koenfeksiyonu olan hastaların HBV DNA yükleri koenfeksiyonu olmayan hastalara kıyasla daha az bulunmuştur. Sonuç: Bu çalışma immünsüprese KHB hastalarının yanında immünkompetan KHB hastalarında da HCMV/EBV koenfeksiyonunun önemli olabileceğini göstermiştir. Kronik HBV hastalarında HCMV/EBV koenfeksiyonun düşük HBV DNA seviyelerine rağmen histolojik aktivite skorlarının yüksek bulunması karaciğer hasarını arttırdığını ve prognozu kötü etkilediğini göstermektedir. Bu yüzden KHB hastalarının HCMV/EBV enfeksiyonu için yüksek risk grupları olarak kabul edilmesi ve bu enfeksiyonlar yönünden takip edilerek tedavi edilmesi hastalığın kötü prognozunu değiştirmede kritik öneme sahip olacağı görüşündeyiz.
References
- 1. Longerich T. Hepatocellular carcinoma. Pathologe. 2020;41(5):478-487. doi: 10.1007/s00292-020-00801.
- 2. Lanini S, Ustianowski A, Pisapia R, Zumla A, Ippolito G. Viral Hepatitis: Etiology, Epidemiology, Transmission, Diagnostics, Treatment, and Prevention. Infect Dis Clin North Am. 2019;33(4):1045-1062. doi: 10.1016/j.idc.2019.08.004.
- 3. Noor A, Panwala A , Forouhar F , Wu GY. Hepatitis caused by herpes viruses: A review. J Dig Dis. 2018;19(8):446-455. doi: 10.1111/1751-2980.12640.
- 4. Polakos NK, Cornejo JC, Murray DA, et al. Kupffercell-dependent hepatitis occurs during influenza infection. Am J Pathol. 2006;168(4):1169-78. doi: 10.2353/ajpath.2006.050875.
- 5. Raghav R, Samour J. Inclusion Body Herpesvirus Hepatitis in Captive Falcons in the Middle East: A Review of Clinical and Pathologic Findings. J Avian Med Surg. 2019;1;33(1):1-6. doi: 10.1647/2018-341.
- 6.Oksuz Z, Serin MS, Serin A, Sezgin O, Gonca S. Determination of reverse transcriptase inhibitör nucleoside analogue resistance profile in pretreatment phase of patients with viral hepatitis B. Mikrobiyol Bul. 2019;53(2):156-169. doi: 10.5578/mb.67796.
- 7. Sezgin O, Altıntaş E, Üçbilek E, Tombak A. Percutaneous Liver Biopsies: Safety and Efficacy. Turkiye Klinikleri J Med Sci. 2010;30(4):1287-91. doi: 10.5336/medsci.2009-13508
- 8. Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. J Hepatol. 2003;38(4):382-6. doi: 10.1002/hep.1840010511.
- 9. Tan L, Sato N, Shiraki A, et al. Everolimus delayed and suppressed cytomegalovirus DNA synthesis, spread of the infection, and alleviated cytomegalovirus infection. Antiviral Res. 2019;162:30-38. doi: 10.1016/j.antiviral.2018.12.004.
- 10. Hwang KA, Ahn JH, Nam JH. Development andvalidation of multiplexreal-time PCR assays for rapid detection of cytomegalovirus, Epstein-Barrvirus, and polyomavirus BK in whole blood from transplant candidates. J Microbiol. 2018;56(8):593-99. doi: 10.1007/s12275-018-8273-2.
- 11. Ryan JL, Fan H, Glaser SL, Schichman SA, Raab-Traub N, Gulley ML. Epstein-Barr virüs quantitation by real-time PCR targeting multiple gene segments: a novel approach to screen for the virus in paraffin-embedded tissue and plasma. J Mol Diagn. 2004;6(4):378-85. doi: 10.1016/S1525-1578(10)60535-1.
- 12. Barcelos F, Martins C, Monteiro R, et al. Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis. Sci Rep. 2021;18;11(1):4082. doi: 10.1038/s41598-021-83550-0.
- 13. Cassaniti I, Cavagna L, Calarota SA, et al. Evaluation of EBV- and HCMV-Specific T Cell Responses in Systemic Lupus Erythematosus (SLE) Patients Using a Normalized Enzyme-Linked Immunospot (ELISPOT) Assay. J Immunol Res. doi: 10.1155/2019/4236503.
- 14. Schuch A, Zecher BF, Müller PA, et al. NK-cell responses are biased towards CD16-mediated effector functions in chronic hepatitis B virus infection. J Hepatol. 2019;70(3):351-360. doi: 10.1016/j.jhep.2018.10.006.
- 15. Hu J, Zhao H, Lou D, et al. Human cytomegalovirus and Epstein-Barr virüs infections, risk factors, and their influence on the liver function of patients with acute-on-chronic liver failure. BMC Infect Dis. 2018;18(1):577. doi: 10.1186/s12879-018-3488-8.
- 16. Lian YL, Wu WF, Shi YM, Liu QC, Tang XP. Preliminary study on relationship between different viral pathogenesis and disease prognosis in patients with severe viral hepatitis. Zhonghua Shi Yan He Lin Chuang Bing DuXueZaZhi. 1999;13(4):355-7.
- 17- Faivre M, Cottet V, Bour JB, et al. Study Group.Impact of Cytomegalovirus Infection on the Outcome of Patients With Cirrhosis: A Preliminary Study, J Clin Gastroenterol. 2019;53(3):236-241. doi: 10.1097/MCG.0000000000001039.
- 18- Varani S, Lazzarotto T, Margotti M, et al. Laboratory signs of acute or recent cytomegalovirus infection are common in cirrhosis of the liver. J MedVirol. 2000;62(1):25-8. doi: 10.1002/1096-9071(200009)62:1
- 19- Giacchino R, Navone C, Ciravegna B, Viscoli C, Ferrea G, Facco F. Livercirrhosis in childhood. Considerations on 22 cases with differentetiology. Pediatr Med Chir. 1990;12(2):147-52.
- 20. An H, Zhou XJ, Miu CM. Clinical study on there lationship between EBV infection and liver diseases infected by HBV. Zhong XI YiJie He GanBingZaZhi. 2005;15:144–5.
- 21. Gallegos-Orozco JF, Rakela-Brödner J. Hepatitis Viruses: Not Always What It Seems to Be. Rev Med Chil. 2010;138(10):1302-11.
- 22. Mellinger JL, Rossaro L, Naugler WE, et al. Epstein-Barrvirus (EBV) related acute liver failure: a case series from the US acute liver failure study group. Dig Dis Sci. 2014;59(7):1630-7. doi: 10.1007/s10620-014-3029-2.
- 23. Cavanaugh VJ, Guidotti LG, Chisari FV. Inhibition of hepatitis B virüs replication during adenovirus and cytomegalovirus infections in transgenic mice. J Virol. 1998;72(4):2630-7. doi: 10.1128/JVI.72.4.2630-2637.
- 24. Rao SC, Ashraf I, Mir F, Samiullah S, Ibdah JA, Tahan V. Dual Infection with Hepatitis B and Epstein Barr Virus Presenting with Severe Jaundice, Coagulopathy, and Hepatitis B Virus Chronicity Outcome. Am J Case Rep. 2017;18:170-172. doi: 10.12659/ajcr.901688.
- 25.Fan J, Jing M, Yang M, et al. Herpesvirus infections in hematopoietic stem cell transplant recipients sero positive for human cytomegalovirus before transplantation. Int J InfectDis. 2016;46:89-93. doi: 10.1182/blood-2005-11-012864.
- 26. Ataman S, Çolak D, Günseren F ve ark. Investigation of Cytomegalovirus Seroepidemiology in Antalya With a Population-Based Cross-Sectional Studyand Review of Related Data in Turkey. Mikrobiyol Bul. 2007;41(4):545-55.
- 27.Renner EL, Dällenbach A. Increased Liver Enzymes: What Should Be Done?. Ther Umsch. 1992;49(5):281-6.
- 28. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Clin Liver Dis (Hoboken). 2018;12(1):33-4. doi: 10.1002/hep.29800.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Articles |
| Authors | |
| Publication Date | August 25, 2021 |
| Submission Date | September 17, 2020 |
| Acceptance Date | April 29, 2021 |
| Published in Issue | Year 2021 Volume: 14 Issue: 2 |
Cite
MEU Journal of Health Sciences Assoc was began to the publishing process in 2008 under the supervision of Assoc. Prof. Gönül Aslan, Editor-in-Chief, and affiliated to Mersin University Institute of Health Sciences. In March 2015, Prof. Dr. Caferi Tayyar Şaşmaz undertook the Editor-in Chief position and since then he has been in charge.
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