Effects of Reactivation of Latent Epstein-Barr Virus Using Polymerase Chain Reaction on Acute Hepatitis A in Children

Seung Hyon Baek; Sang Yong Kim; Hong Koh

doi:10.5223/kjpgn.2011.14.1.59

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Baek, Kim, and Koh: Effects of Reactivation of Latent Epstein-Barr Virus Using Polymerase Chain Reaction on Acute Hepatitis A in Children

Original Article

Liver & Bile Duct

Korean Journal of Pediatric Gastroenterology and Nutrition

Korean Journal of Pediatric Gastroenterology and Nutrition 2011; 14(1): 59-66.

Published online: 31 March 2011

DOI: https://doi.org/10.5223/kjpgn.2011.14.1.59

Effects of Reactivation of Latent Epstein-Barr Virus Using Polymerase Chain Reaction on Acute Hepatitis A in Children

Seung Hyon Baek, M.D., Sang Yong Kim, M.D.^*, Hong Koh, M.D.^*

Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.

^*Severance Pediatric Liver Disease Research Group, Severance Children's Hospital, Seoul, Korea.

Corresponding author (khong@yuhs.ac)

Received 9 August 2010 Revised 28 August 2010 Accepted 28 August 2010

Abstract

Purpose

We previously reported that concurrent reactivation of latent Epstein-Barr virus (EBV) in children with hepatitis A virus (HAV) infection is common and EBV reactivation with HAV infection adversely affects the clinical features of hepatitis. However, the incidence of concurrent reactivation was not accurate because the detection of EBV reactivation was based on serologic methods. Therefore, we studied the effects of polymerase chain reaction (PCR)-proven EBV reactivation, thus a more precise concurrence, on acute HAV infection in children.

Methods

PCR were conducted in 34 patients, who had enrolled previous study and diagnosed with acute HAV infection between January 2008 and June 2010. Their medical records were reviewed.

Results

Among 34 patients with acute HAV infection, 12 patients (35.3%) had EBV reactivation which was proven using serologic and molecular biologic techniques. There were significant differences in the peak levels of AST and ALT between the reactivated and non-reactivated groups (p=0.001 and p<0.001, respectively). The duration of full recovery from hepatitis was more prolonged in the reactivated group (p<0.001). Clinical parameters, such as serum protein (p<0.001) and albumin concentrations (p<0.001), atypical lymphocyte count (p=0.001), prothrombin time-international normalized ratio (PT-INR, p<0.001), and splenomegaly (p<0.001), showed significant differences. The clinical features in the reactivated sub-group >10 years of age revealed more liver dysfunction compared to the non-reactivated sub-group. A comparison with a previous study was performed.

Conclusion

PCR-proven reactivation of latent EBV in children with HAV infection is common and EBV reactivation with HAV infection adversely affects the clinical features of hepatitis, especially in older children.

Keywords: Epstein-Barr virus, Acute hepatitis A, Polymerase chain reaction

Figures and Tables

Table 1

Clinical Characteristics of the Patients and Correlation between Non-reactivated and Reactivated EBV Infection Groups

EBV: Epstein-Barr virus, AST: aspartate aminotransferase, ALT: alanine aminotransferase, Atyp lym: atypical lymphocyte, Duration: duration of full recovery from hepatitis, PT-INR: prothrombin time-international normalized ratio, GGT: r-glutamyl-transpeptidase, ALP: Alkaline phosphatase, T.bil: total bilirubin, D.bil: direct bilirubin, WBC: white blood cell, Lym: lymphocyte, All date show mean±SD.

Table 2

Clinical Characteristics and Correlation of Patients according to Status of EBV Infection in the Two Age Groups

Table 3

Comparison between the Serologic and PCR Method Study Results

Duration: duration of full recovery from hepatitis, AST: aspartate aminotransferase, ALT: alanine aminotransferase, PT-INR: prothrombin time-international normalized ratio.

Table 4

Comparison between Serologic and PCR Method Study according to Age Groups

Duration: duration of full recovery from hepatitis, PT-INR: prothrombin time-international normalized ratio, AST: aspartate aminotransferase, ALT: alanine aminotransferase

References

1. El-Kamary SS, Cheng TL. Hepatitis A. Pediatr Rev. 2005. 26:75–76.

2. Jung YK, Kim JH. Epidemiology and clinical features of acute hepatitis A: from the domestic perspective. Korean J Hepatol. 2009. 15:438–445.

3. Hallee TJ, Evans AS, Niederman JC, Brooks CM, Voegtly H. Infectious mononucleosis at the United States Military Academy. A prospective study of a single class over four years. Yale J Biol Med. 1974. 47:182–195.

4. Asano N, Yamamoto K, Tamaru J, Oyama T, Ishida F, Ohshima K, et al. Age-related Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders: comparison with EBV-positive classic Hodgkin lymphoma in elderly patients. Blood. 2009. 113:2629–2636.

5. Gotlieb-Stematsky T, Rannon L, Vonsover A, Varsano N. Stimulation of antibodies to Epstein-Barr virus (EBV) in acute viral infections. Arch Virol. 1978. 57:199–204.

6. Stowe RP, Pierson DL, Barrett AD. Elevated stress hormone levels relate to Epstein-Barr virus reactivation in astronauts. Psychosom Med. 2001. 63:891–895.

7. Nystad TW, Myrmel H. Prevalence of primary versus reactivated Epstein-Barr virus infection in patients with VCA IgG-, VCA IgM- and EBNA-1-antibodies and suspected infectious mononucleosis. J Clin Virol. 2007. 38:292–297.

8. Besnard M, Faure C, Fromont-Hankard G, Ansart-Pirenne H, Peuchmaur M, Cezard JP, et al. Intestinal pseudo-obstruction and acute pandysautonomia associated with Epstein-Barr virus infection. Am J Gastroenterol. 2000. 95:280–284.

9. Drebber U, Kasper HU, Krupacz J, Haferkamp K, Kern MA, Steffen HM, et al. The role of Epstein-Barr virus in acute and chronic hepatitis. J Hepatol. 2006. 44:879–885.

10. Lavin AC, Roman JG, Zarate SA, Porras MC, Caviedes JR. Acute upper gastrointestinal bleeding associated with Epstein-Barr virus reactivation in an immunocompetent patient. Am J Gastroenterol. 2009. 104:253–254.

11. Rajwal S, Davison S, Wyatt J, McClean P. Primary Epstein-Barr virus hepatitis complicated by ascites with epstein-barr virus reactivation during primary cytomegalovirus infection. J Pediatr Gastroenterol Nutr. 2003. 37:87–90.

12. Touge C, Agawa H, Sairenji T, Inoue Y. High incidence of elevated antibody titers to Epstein-Barr virus in patients with uveitis. Arch Virol. 2006. 151:895–903.

13. Kim SY, Ryu IS, Baek SH, Chung KS, Koh H. Concurrent reactivation of latent EBV with hepatitis A can affect clinical feature of childhood hepatitis. Acta Paediatr. 2010. 99:1258–1262.

14. Obel N, Hoier-Madsen M, Kangro H. Serological and clinical findings in patients with serological evidence of reactivated Epstein-Barr virus infection. APMIS. 1996. 104:424–428.

15. Chung JL, Kim HS. Clinical usefulness of EBV-specific antibody panel test and PCR genotyping in the diagnosis of Epstein-Barr virus infection. Korean J Clin Pathol. 2000. 20:320–329.

16. Luderer R, Kok M, Niesters HG, Schuurman R, de Weerdt O, Thijsen SF. Real-time Epstein-Barr virus PCR for the diagnosis of primary EBV infections and EBV reactivation. Mol Diagn. 2005. 9:195–200.

17. Rowe M, Zuo J. Immune responses to Epstein-Barr virus: molecular interactions in the virus evasion of CD8+ T cell immunity. Microbes Infect. 2010. 12:173–181.

18. Ternak G. Epstein-Barr virus reactivation. Lancet Infect Dis. 2003. 3:271.

19. Siegl G, Weitz M. Pathogenesis of hepatitis A: persistent viral infection as basis of an acute disease? Microb Pathog. 1993. 14:1–8.

20. Vallbracht A, Maier K, Stierhof YD, Wiedmann KH, Flehmig B, Fleischer B. Liver-derived cytotoxic T cells in hepatitis A virus infection. J Infect Dis. 1989. 160:209–217.

21. Rickinson AB, Moss DJ, Allen DJ, Wallace LE, Rowe M, Epstein MA. Reactivation of Epstein-Barr virus-specific cytotoxic T cells by in vitro stimulation with the autologous lymphoblastoid cell line. Int J Cancer. 1981. 27:593–601.

22. Fukuda M, Satoh TA, Takanashi M, Hirai K, Ohnishi E, Sairenji T. Inhibition of cell growth and Epstein-Barr virus reactivation by CD40 stimulation in Epstein-Barr virus-transformed B cells. Viral Immunol. 2000. 13:215–229.

23. Annels NE, Kalpoe JS, Bredius RG, Claas EC, Kroes AC, Hislop AD, et al. Management of Epstein-Barr virus (EBV) reactivation after allogeneic stem cell transplantation by simultaneous analysis of EBV DNA load and EBV-specific T cell reconstitution. Clin Infect Dis. 2006. 42:1743–1748.

24. Asada H, Miyagawa S, Sumikawa Y, Yamaguchi Y, Itami S, Suguri S, et al. CD4+ T-lymphocyte-induced Epstein-Barr virus reactivation in a patient with severe hypersensitivity to mosquito bites and Epstein-Barr virus-infected NK cell lymphocytosis. Arch Dermatol. 2003. 139:1601–1607.

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