Alphania Rahniayu, Gondo Mastutik, Willy Sandhika, S. Eriaty N. Ruslan, Anny Setijo Rahaju, Bagus Setyoboedi, Erna Sulistyani
firstname.lastname@example.org , email@example.com
Alphania Rahniayu1,2, Gondo Mastutik1*, Willy Sandhika1,2, S. Eriaty N. Ruslan3, Anny Setijo Rahaju1,2, Bagus Setyoboedi4,5, Erna Sulistyani6
1Department of Anatomic Pathology, Faculty of Medicine, Universitas Airlangga, Surabaya-60132, Indonesia.
2Department of Anatomic Pathology, Dr. Soetomo General Academic Hospital, Surabaya-60132, Indonesia.
3Institute of Tropical Diseases, Universitas Airlangga, Surabaya-60132, Indonesia.
4Department of Child Health of Pediatric, Faculty of Medicine, Universitas Airlangga, Surabaya-60132, Indonesia.
5Department of Child Health of Pediatric, Dr. Soetomo General Academic Hospital, Surabaya-60132, Indonesia.
6Department of Oral Medicine, Faculty Dentistry, Jember University, Jember-68121, Indonesia.
Volume - 15,
Issue - 6,
Year - 2022
Introduction: Human cytomegalovirus (HCMV) is associated with cholestasis in infants. Diagnosis of HCMV infection is most often based on serological anti-HCMV. Identification of HCMV in liver tissue has been rarely reported. The aims of this study were to determine the presentation of HCMV in liver tissues and to analyze its association with serological anti-HCMV of cholestatic infants with extrahepatic and non-extrahepatic biliary atresia. Methods: This observational study was performed during December 2017- December 2018 with ethics from our institutions. The parents or guardians of subjects signed the informed consent. Anti-HCMV serological data were collected from patient medical records. Histopathological diagnosis and polymerase chain reaction (PCR) for HCMV were performed from liver biopsy tissues. The data were analyzed by Chi-square. Results: There were 47 cholestatic infants, 38.3% EBA and 61.7% non-EBA. Anti-HCMV IgM was positive in 38.3% patients and IgG was positive in 91.5% patients. Acute infection or recent infection were 38.3%, past or not acute infection were 53.1%, and uninfected or early infection were 8.5% patients. The presentation of HCMV in liver tissues was 68.1% patients, consisting of 11/18 EBA and 21/29 non-EBA and negative in 31.9% patients, consisting of 7/18 EBA and 8/29 non-EBA. There was no association between serological anti-HCMV and PCR HCMV with histopathological features. Conclusion: It suggests that PCR can be used as a routine tool to detect the presentation of HCMV DNA in liver tissue. Type of cholestasis in infants, both EBA and non-EBA, cannot be determined based on the serological and PCR examination, but based on histopathological features.
Cite this article:
Alphania Rahniayu, Gondo Mastutik, Willy Sandhika, S. Eriaty N. Ruslan, Anny Setijo Rahaju, Bagus Setyoboedi, Erna Sulistyani. Presentation of Human Cytomegalovirus (HCMV) in Liver Tissues of Cholestatic Infants with Extrahepatic and Non-Extrahepatic Biliary Atresia. Research Journal of Pharmacy and Technology. 2022; 15(6):2486-2. doi: 10.52711/0974-360X.2022.00415
Alphania Rahniayu, Gondo Mastutik, Willy Sandhika, S. Eriaty N. Ruslan, Anny Setijo Rahaju, Bagus Setyoboedi, Erna Sulistyani. Presentation of Human Cytomegalovirus (HCMV) in Liver Tissues of Cholestatic Infants with Extrahepatic and Non-Extrahepatic Biliary Atresia. Research Journal of Pharmacy and Technology. 2022; 15(6):2486-2. doi: 10.52711/0974-360X.2022.00415 Available on: https://rjptonline.org/AbstractView.aspx?PID=2022-15-6-19
1. Mack CL. What causes billiary atresia? Unique aspects of the neonatal immune system provide clues to disease pathogenesis. Cellular Molecular Gastroenterology and Hepatology. 2015; 1(3):267-74. https://doi.org/10.1016/j.jcmgh.2015.04.001
2. Fischler B. Lamireau T. Cholestasis in the newborn and infant. Clinics and Research in Hepatology and Gastroenterology. 2014; 38(3): 263-7. https://doi.org/10.1016/j.clinre.2014.03.010
3. Min CY. Song JY. Jeong SJ. Characteristics and prognosis of hepatic cytomegalovirus infection in children: 10 years of experience at a university hospital in Korea. Korean Journal of Pediatrics. 2017; 60(8):261.https://doi.org/10.3345/kjp.2017.60.8.261
4. Tanimura K. Yamada H. Potential biomarkers for predicting congenital cytomegalovirus infection. International Journal of Molecular Sciences. 2018; 19(12):3760. https://doi.org/10.3390/ijms19123760
5. De Tommaso AM. Andrade PD. Costa SC. Escanhoela CA. Hessel G. High frequency of human cytomegalovirus DNA in the liver of infants with extrahepatic neonatal cholestasis. BMC Infectious Disease. 2005; 5(1):1-8). https://doi.org/10.1186/1471-2334-5-108.
6. Feldman AG. Sokol RJ. Neonatal cholestasis. Neoreviews. 2013; 14(2):e63-73. https://doi.org/10.1542/neo.14-2-e63
7. Davis AR. Rosenthal P. Escobar GJ. Newman TB. Interpreting conjugated bilirubin levels in newborns. The Journal of Pediatrics. 2011; 158(4): 562-5. https://doi.org/10.1016/j.jpeds.2010.09.061
8. Rashed YK. Saber MA. Tawfik M. Mourad WS. Histopathological features and accuracy for diagnosing biliary atresia by prelaparotomy liver biopsy in Egypt. Egyptian Pediatric Association Gazette. 2013; 61(1): 42–5. https://doi.org/10.1016/j.epag.2013.05.001
9. Stehel EK. Sánchez PJ. Cytomegalovirus infection in the fetus and neonate. Neoreviews. 2005; 6(1):e38-45. https://doi.org/10.1542/neo.6-1-e38.
10. Soetens O. Vauloup-Fellous C. Foulon I. Dubreuil P. De Saeger B. Grangeot-Keros L. Naessens A. Evaluation of different cytomegalovirus (CMV) DNA PCR protocols for analysis of dried blood spots from consecutive cases of neonates with congenital CMV infections. Journal of Clinical Microbiology. 2008; 46(3):943-6. https://doi.org/10.1128/JCM.01391-07.
11. Goegebuer T. Van Meensel B. Beuselinck K. Cossey V. Van Ranst M. Hanssens M. Lagrou K. Clinical predictive value of real-time PCR quantification of human cytomegalovirus DNA in amniotic fluid samples. Journal of Clinical Microbiology. 2009; 47(3):660-5. https://doi.org/10.1128/JCM.01576-08.
12. Suchy FJ. Neonatal cholestasis. Pediatrics in Review. 2004; 25(11): 388-96. https://doi.org/10.1542/pir.25-11-388
13. Zagory JA. Nguyen MV. Wang KS. Recent advances in the pathogenesis and management of biliary atresia. Current Opinion in Pediatrics. 2015; 27(3):389. https://doi.org/10.1097/MOP.0000000000000214
14. Rastogi A. Krishnani N. Yachha SK. Khanna V. Poddar U. Lal R. Histopathological features and accuracy for diagnosing biliary atresia by prelaparotomy liver biopsy in developing countries. Journal of Gastroenterology and Hepatology. 2009; 24(1):97-102. https://doi.org/10.1111/j.1440-1746.2008.05737.x.
15. Poddar U. Thapa BR. Das A. Bhattacharya A. Rao KL. Singh K. Neonatal cholestasis: differentiation of biliary atresia from neonatal hepatitis in a developing country. Acta Paediatrica. 2009; 98(8):1260-4. https://doi.org/10.1111/j.1651-2227.2009.01338.x
16. Oliviera NL. Kanawaty FR. Costa S. Hessel G. Infection by cytomegalovirus in patients with neonatal cholestasis. Arquivos de Gastroenterologia. 2002; 39(2): 132-6. https://doi.org/10.1590/s0004-28032002000200012
17. Pawlowska J. Swiatkowska E. Gliwicz D. Jankowska I. Kluge P. Cukrawska B. Dzierżanowski-Fangrat K. The role of cytomegalovirus infection in pathogenesis of neonatal cholestasis. Experimental & Clinical Hepatology.2010;6(1):25–9.
18. Russo P. Magee JC. Anders RA. Bove KE. Chung C. Cummings OW. Finegold MJ. Finn LS. et al. Childhood Liver Disease Research Network (ChiLDReN). Key Histopathologic Features of Liver Biopsies That Distinguish Biliary Atresia from Other Causes of Infantile Cholestasis and Their Correlation with Outcome: A Multicenter Study. The American Journal of Surgical Pathology. 2016 Dec;40(12):1601-1615. https://doi.org/10.1097/PAS.0000000000000755.
19. McDonald GB. Sarmiento JI. Rees-Lui G. Myerson D. Cytomegalovirus hepatitis after bone marrow transplantation: An autopsy study with clinical, histologic and laboratory correlates. Journal of Viral Hepatitis. 2019; 26(11):1344-1350. https://doi.org/10.1111/jvh.13176
20. Moore SW. Zabiegaj-Zwick C. Nel E. Problems related to CMV infection and biliary atresia. South African Medical Journal. 2012; 102(11):890-2. https://doi.org/10.7196/samj.6163
21. Ross SA. Novak Z. Pati S. Boppana SB. Diagnosis of Cytomegalovirus Infections. Infectious Disorders Drug Targets. 2011; 11(5): 466–74. https://doi.org/10.2174/187152611797636703
22. Fischler B. Ehrnst A. Forsgren M. Orvell C. Nemeth A. The viral association of neonatal cholestasis in Sweden: a possible link between cytomegalovirus infection and extrahepatic biliary atresia. Journal of Pediatric Gastroenterology and Nutrition. 1998; 27(1): 57-64. https://doi.org/10.1097/00005176-199807000-00010
23. Sira MM. Sira AM. Elhenawy IA. Khalil FO. Prevalence of serological markers of TORCH infections in biliary atresia and other neonatal cholestatic disorders. Open Journal of Pediatric and Child Health. 2016; 2(1):013–7. https://doi.org/10.17352/2640-7612.000010
24. Goel A. Chaudhari S. Sutar J. Bhonde G. Bhatnagar S. Patel V. Bhor V. Shah I. Detection of Cytomegalovirus in Liver Tissue by Polymerase Chain Reaction in Infants with Neonatal Cholestasis. Pediatric Infectious Disease Journal. 2018; 37(7): 632-6. https://doi.org/10.1097/INF.0000000000001889
25. Slobedman B. Mocarski ES. Quantitative analysis of latent human cytomegalovirus. Journal of Virology. 1999; 73(6):4806-12. https://doi.org/10.1128/JVI.73.6.4806-4812.1999
26. Mastutik G. Kurniasari N. Rahniayu A. Rahaju AN. Ruslan SEN. Ilmiah K. Setyoboedi B. Sulistyani E. Detection of cytomegalovirus in urine specimen of cholestatic infants by polymerase chain reaction. Research Journal of Pharmacy and Technology. 2022; 15(5):2151-7. http://doi: 10.52711/0974-360X.2022.00357.