• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10489-10493
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• 2015

Background: Gastric cancer is the second most common gastrointestinal cancer and is largely attributed to Helicobacter pylori (H. pylori) infection. In addition, studies have also shown association with Epstein-Barr virus (EBV) in 10% of gastric cancers. This study assessed the characteristics of EBV associated gastric cancers (EBVaGC) in Brunei Darussalam. Materials and Methods: This study included gastric cancers diagnosed between 2008 and 2012, registered with the Department of Pathology RIPAS Hospital, Brunei Darussalam. Clinical case notes were systematically reviewed. Histology specimens were all stained for EBV and also assessed for intestinal metaplasia and H. pylori. Results: There were a total of 81 patients (54 male and 27 females) with a mean age of $65.8{\pm}14.8years$ included in the study. Intestinal metaplasia and active H. pylori infection were detected in 40.7% and 30.9% respectively. A majority of the tumors were proximally located (55.6%), most poorly differentiated (well differentiated 16%, moderately differentiated 30.9% and poorly differentiated 53.1%) and the stages at diagnosis were; stage I (44.4%), stage II (23.5%), stage III (8.6%) and stage IV (23.5%). EBV positivity (EBVaGC) was seen in 30.9%. Between EBVaGC and EBV negative gastric cancers, there were no significant differences (age, gender, ethnic group, presence of Intestinal metaplasia, tumor locations, stages of disease and degree of tumor differentiation). Conclusions: This study showed that a third of gastric cancers in Brunei Darussalam were positive for EBV, higher than what have been reported in the literature. However, there were no significant differences between EBVaGC and EBV negative gastric cancers. This suggests that the role of EBV in gastric cancer may be mostly incidental rather than any causal relation. However, further studies are required.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.1
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• pp.38-43
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• 2012

Purpose: Epstein-Barr virus (EBV) hepatitis is a usually asymptomatic and self-limiting disease in immunocompetent patients. However, the range of severity is wide, and the serological diagnosis is typically difficult until the convalescent phase. Thus, we examined the value of plasma EBV DNA real-time quantitative polymerase chain reaction (RT-qPCR) in EBV hepatitis for the timely diagnosis and the relationship between EBV viral load and clinical severity. Methods: Sixty samples were confirmed as having EBV infection by RT-qPCR with the EBV BALF5 gene sequence. We examined the clinical characteristics of EBV hepatitis by reviewing medical records. Results: The median total duration of fever was 8 days (range: 0-13 days). The mean peak value of aspartate aminotransferase (AST) was $241{\pm}214$ U/L, and the mean peak value of alanine aminotransferase (ALT) was $298{\pm}312$ U/L. There was no correlation between the serum levels of liver enzyme and plasma EBV DNA titer ($p$=0.1) or between median total duration of fever and EBV DNA titer ($p$=0.056). The median age of the EBV VCA IgM-negative group was lower compared with the EBV VCA IgM-positive group in EBV hepatitis (2 years vs. 6 years, $p$=0.0009). Conclusion: The severity of EBV hepatitis does not correlate with circulating EBV DNA load according to our data. Furthermore, we suggest that plasma EBV PCR may be valuable in young infants in whom the results of serology test for EBV infection commonly are negative.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.398-410
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• 2011

Over the past few decades, our understanding of the epidemiology and immunopathogenesis of Hodgkin lymphoma (HL) has made enormous advances. Consequently, the treatment of HL has changed significantly, rendering this disease of the most curable human cancers. To date, about 80% of patients achieve long-term disease-free survival. However, therapeutic challenges still remain, particularly regarding the salvage strategies for relapsed and refractory disease, which need further identification of better prognostic markers and novel therapeutic schemes. Although the precise molecular mechanism by which Epstein-Barr virus (EBV) contributes to the generation of malignant cells present in HL still remains unknown, current increasing data on the role of EBV in the pathobiology of HL have encouraged people to start developing novel and specific therapeutic strategies for EBV-associated HL. This review will provide an overview of therapeutic approaches for acute EBV infection and the classical form of HL (cHL), especially focusing on EBV-associated HL cases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7459-7465
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• 2014

Background: A prior study showed blood type A/AB to be associated with an increased risk of nasopharyngeal carcinoma (NPC) compared to subjects with blood type O. However, the relationship between ABO blood groups and prognosis of NPC patients is still questionable. In addition, whether Epstein-Barr virus (EBV) infection is associated with prognosis of NPC patients with different ABO blood groups is unclear. Materials and Methods: We conducted univariate and multivariable Cox regression analyses based on a consecutive cohort of 1,601 patients to investigate the above issues. Results: There was no significant difference in overall survival (OS) between different ABO blood groups (p=0.629), neither between A vs. non-A blood groups (p=0.895) nor AB vs. non-AB blood group (p=0.309) in univariate analyses and after adjusting for other factors. Interaction tests revealed that high immunoglobulin A against Epstein-Barr virus viral capsid antigen (VcA-IgA) level was associated with a favorable prognosis in male patients with UICC stage II disease who had an A blood type (p=0.008), compared with those with non-A blood type. In addition, male patients with an A blood group with a high blood lymphocyte level showeda tendency towards better survival in UICC stage III (p=0.096). Conclusions: ABO blood group status is not associated with the prognosis of patients with NPC. Additionally, blood group A male NPC patients with high VcA-IgA level or high blood lymphocyte counts might be correlated with a favorable prognosis in UICC stage II or III, respectively.

• Pediatric Infection and Vaccine
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• v.24 no.1
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• pp.44-53
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• 2017

Purpose: The aim of this study was to investigate the risk factors for posttransplant lymphoproliferative disorder (PTLD) and to evaluate the association between Epstein-Barr viral load and the development of PTLD in pediatric heart transplant recipients. Methods: We reviewed children aged <18 years who underwent heart transplantation and quantitative analysis of blood Epstein-Barr virus (EBV) viremia at our institute from January 2006 to March 2015. Clinical characteristics and EBV viral loads were compared according to the presence of PTLD. Results: Over 9 consecutive years, a total of 40 heart transplant recipients, were included. Among 28 children with available EBV viral load measurements, seven patients (25%) had EBV viremia only defined as at least one time of ${\geq}457copies/mL$. PTLD occurred in three recipients (7.5%) 4.3, 6.3, and 17.0 months after transplant and all PTLD cases had preceding EBV viremia. The median age at transplant was 5.3 years (range, 0.5 to 6.0 years) in the PTLD group, compared with 11.9 years (range, 0.3 to 17.8 years) in the non-PTLD group (P=0.021). The median values of the peak EBV levels in the PTLD group were 3,452,170 copies/mL (range, 46,750 to 7,622,910 copies/mL); the peak EBV levels in the non-PTLD group were 3,112 copies/mL (range, 2,250 to 103,000 copies/mL). Conclusions: Younger age at transplant and presence of EBV viremia were associated with the development of PTLD in pediatric heart transplant recipients. A prospective study will be required to determine the blood EBV load for predicting the development of PTLD in these patients.

• Clinical and Experimental Pediatrics
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• v.54 no.10
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• pp.409-413
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• 2011

Purpose: Few studies have been conducted on the recent status of infectious mononucleosis (IM) in Korean children. The aim of this study was to evaluate the recent trend in the clinical manifestations of Epstein-Barr virus (EBV)-associated IM as well as the clinical differences according to age. Methods: A retrospective study was performed on 81 children hospitalized with EBV-associated IM who fulfilled the serological criteria for the diagnosis of EBV infection (viral capsid antigen immunoglobulin M positive). The patients were divided into 3 age groups: <5 years, 5 to 9 years, and ${\geq}10$ years. We evaluated the recent trend in clinical manifestations and the differences in clinical and laboratory findings among the 3 age groups. Results: Thirty (37%) children were under 5 years of age, 38 (46.9%) were 5 to 9 years of age, and 13 (16%) were 10 years of age or older. The differences in the symptoms and signs among the 3 age groups were not statistically significant, except for headache. The mean duration of fever was 7.7 days (range, 0 to 18 days). A comparison of liver enzyme elevation among the age groups showed an association with advancing age (26.6%, 63.1%, and 76.9%, respectively, P=0.04) Conclusion: This study showed that EBV-associated IM in Korean children continues to occur mostly in children under 10 years of age. In children with EBV-associated IM, the incidence of headache and liver enzyme elevation, the duration of fever, and the proportion of females to males were all positively associated with advancing age.

• Childhood Kidney Diseases
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• v.12 no.1
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• pp.88-92
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• 2008

Infection of Epstein-Barr virus(EBV) gives rise to a broad spectrum of clinical manifestations in children. Although renal involvement is rare, diverse renal manifestations are known from hematuria to acute renal failure. Secondary membranous nephropathy(MN) associated with systemic EBV infection is an uncommon renal pathology and only two cases have been reported. We are adding another case of MN associated with EBV infection in a child. An 8-year-old girl was admitted for renal biopsy. She had been followed up for microscopic hematuria and intermittent proteinuria for 5 months. There had been no specific findings in serology and radiology. Tonsil biopsy had been done due to exudative tonsillar hypertrophy and enlarged multiple cervical lymph nodes. And it showed EBV-associated lymphoproliferative findings. Serologic tests for EBV showed positive evidence of recent infection; viral capsid antigen(VCA) IgM was borderline positive, VCA IgG and early antigen IgG were positive, and EB nuclear antigen IgG was negative. In Situ Hybridization of tonsil for EBV mRNA was positive. Because her proteinuria and hematuria were aggravated at that time(protein 3 +, RBC >60/HPF), renal biopsy was done. Renal biopsy showed the findings of MN, characterized by thickened capillary walls with epimembranous spikes on light microscopy and subepithelial, mesangial and subendothelial electron dense deposits on electron microscopy. On immunofluorescence microscopy, IgG, C1q, kappa and lambda chains were positive. After steroid administration, proteinuria and hematuria resolved gradually within 6 months.

• Clinical and Experimental Pediatrics
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• v.57 no.9
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• pp.420-424
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• 2014

The Epstein-Barr virus (EBV) is oncogenic and can transform B cells from a benign to a malignant phenotype. EBV infection is also associated with lymphoid interstitial pneumonia (LIP). Here, we report the case of a 14-year-old boy who was diagnosed with a latent EBV infection and underlying LIP, without any associated immunodeficiency. He had been EBV-seropositive for 8 years. The first clinical presentations were chronic respiratory symptoms and recurrent pneumonia. The symptoms worsened in the following 2 years. The results of in situ hybridization were positive for EBV, which led to a diagnosis of LIP. The diagnosis was confirmed by the results of a thoracoscopic lung biopsy. The EBV titer of the bronchoalveolar lavage specimens obtained after acyclovir treatment was found to be fluctuating. The patient had latent EBV infection for 8 years, until presented at the hospital with intermittent abdominal pain and distension. Physical examination and pelvic computed tomography revealed a large mesenteric mass. A biopsy of the excised mass led to a diagnosis of Burkitt's lymphoma (BL). The patient received combination chemotherapy for 4 months, consisting of vincristine, methotrexate, cyclophosphamide, doxorubicin, and prednisolone. He is now tumor-free, with the LIP under control, and is being followed-up at the outpatient clinic. This is the first report of a Korean case of chronic latent EBV infection that developed into LIP and BL in a nonimmunocompromised child.

• Pediatric Infection and Vaccine
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• v.27 no.2
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• pp.117-126
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• 2020

Purpose: Epstein-Barr virus (EBV) infection is related to infectious mononucleosis or nasopharyngeal cancer, and its epidemiology may change according to the socioeconomic development of communities. This study aimed to evaluate the recent epidemiology of EBV seropositive rate in Korea. Methods: We retrospectively reviewed EBV serology test results obtained from a part of clinical care at Samsung Medical Center, Seoul, South Korea, from January 2000 to December 2017. Results: The EBV seropositive rate in 26,527 subjects during the study period was 81.0% (21,485/26,527): 44.4% (2,716/6,122) in subjects aged 0-9 years, 75.8% (2,077/2,739) in those aged 10-19 years, and 94.5% (16,692/17,666) in those aged ≥20 years. The EBV seropositive rate decreased from 89.4% (8,592/9,616) in 2000-2008 to 76.2% (12,893/16,911) in 2009-2017 (P<0.001). Especially, the EBV seropositive rate in subjects aged 0-19 years significantly decreased from 2000-2008 to 2009-2017 (0-9 years, 62.8% [1,172/1,866] in 2000-2008 and 36.3% [1,544/4,256] in 2009-2017; 10-19 years, 83.8% [745/858] in 2000-2008 and 70.8% (1,332/1,881) in 2009-2017) (P<0.001). Conclusions: The EBV seropositive rate in children has decreased in the last 20 years. As the age of patients with primary EBV infection increased, there is a need for interest in clinical manifestation, such as infectious mononucleosis, in adolescents and young adults.

• Pediatric Infection and Vaccine
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• v.4 no.1
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• pp.167-173
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• 1997

Acute infectious mononucleosis, caused by Epstein-Barr virus(EBV), is a self limited lymphoproliferative illness that is common in adolescents and young adults. It shows many complications in multiple organ systems, but the hepatobiliary and the respiratory complication is uncommon. We report a case with thickened gallbladder wall and pneumonia as complications of acute infectious mononucleosis in a child. Also the related literature were reviewed. A 4 year old boy presented with a history of high fever, cough, and abdominal distension for 20days. Physical Examination revealed audible crackles in whole lung field and gross hepatomegaly. Chest X-ray showed pneumonia and liver function tests were abnormal. Ultrasonography and computed tomography revealed a thickened gallbladder wall and hepatosplenomegaly. The diagnosis of primary Epstein-Barr viral infection was eventually made by specific serologic tests. The patients's fever subsided 6 weeks later and pneumonia was recovered around this time. Liver function tests returned near normal 2 months later and ultrasonography of gallbladder was normal at this time.