• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.2
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• pp.91-99
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• 2012

Purpose: The aims of this study was to compare and evaluate the clinical characteristics, laboratory data, and prognosis for infants under age 1 year with CMV hepatitis and those with viral hepatitis of unknown etiology. Methods: A retrospective study was conducted of infants under age 1 year who were admitted with acute hepatitis. The exclusion criteria consisted of: autoimmune, genetic, metabolic, toxic, HAV, HBV, HCV, toxoplasma, rubella, herpes simplex, and Epstein-Barr virus. The 30 patients included were divided into two groups based on markers for CMV (IgM anti-CMV, CMV PCR in urine, CMV culture in urine). Results: The median age of patients (n=15) was 2.8 months. No other organ involvement was detected in any patient. Peak serum total bilirubin levels (n=4) ranged from 2.6 to 6.7 mg/dL. Peak serum ALT levels ranged from 51 to 1,581 IU/L. The duration of ALT elevation ranged from 1.5 weeks to 26 weeks (median 9 weeks). All had recovered in full without ganciclovir; there were no cases of hearing loss. The median age of controls (n=15) was 2.5 months. Peak serum total bilirubin levels (n=4) ranged from 1.6 to 9.1 mg/dL. Peak serum ALT levels ranged from 26 to 1,794 IU/L. No significant differences were observed between both groups regarding the peak serum ALT levels, peak serum total bilirubin levels, duration of hyperbilirubinemia and ALT elevation. Conclusion: Although it was not possible to differentiate congenital infection with perinatal infection in this study, the prognosis of patients with CMV hepatitis without other organ involvement was good without ganciclovir treatment.

• Clinical and Experimental Pediatrics
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• v.60 no.8
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• pp.261-265
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• 2017

Purpose: Studies on cytomegalovirus (CMV) infections in immunocompetent children are lacking, and minimal information is available in the medical literature on hepatic manifestations and complications of CMV. The aims of this study were to evaluate the clinical characteristics, laboratory data, and prognosis of children with CMV hepatitis, and to investigate its prevalence at a single medical center in Korea over a 10-year period. Methods: One hundred thirty-two children diagnosed with CMV infection based on specific markers (anti-CMV IgM, CMV polymerase chain reaction in blood and urine, or CMV culture of urine) were included in the study. Clinical and biochemical characteristics, immunological markers, and outcomes of hepatic CMV infection were determined. Results: The median age of patients (n=132) was 8.5 months (range, 14 days-11.3 years). Peak total bilirubin and alanine aminotransferase levels in serum ranged from 0.11-21.97 mg/dL, and 5-1,517 IU/L, respectively. Alanine aminotransferase remained elevated from 2-48 weeks. Jaundice was the most common clinical feature of hepatic CMV infection during infancy. The hematologic findings revealed anemia, leukocytosis, and monocytosis in CMV-infected patients. All participants recovered without administration of ganciclovir. Conclusion: In children with CMV hepatitis, fever was the most common symptom at presentation, and jaundice was the most common clinical feature of hepatic CMV infection in infants younger than 3 months of age. Hepatic CMV infection in immunocompetent children is often a self-limited illness that does not require antiviral therapy, as most patients in this study had favorable outcomes.

• Korean Journal of Microbiology
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• v.43 no.1
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• pp.1-6
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• 2007

We describe a multiplex PCR method that can detect and differentiate simultaneously four different kinds of DNA viruses, Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B virus (HBV) and parvovirus B19 (B19). Primers for the multiplex PCR reaction were designed to amplify specific regions of the EBV (pol), CMV (pol), HBV (pol) and B19 (ns) viral genomes and used to simultaneously detect individual viruses. In order to achieve optimal sensitivity and specificity for multiplex PCR, the thermo-cycling parameters, primer sequences, and concentration of each reaction components were optimized systematically. The sensitivity of the detection method ranged between 5 and 10 copies of viral genome with a mixture of multiple primer pairs. Furthermore, this highly sensitive test showed no cross-reactivity among the four viruses. Thus, the results obtained in this study provide evidence that the assay system is a good tool for supporting the diagnosis of viral infection and contamination.

• Molecules and Cells
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• v.22 no.2
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• pp.175-181
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• 2006

Delivery of DNA vaccines to airway mucosa would be an ideal method for mucosal immunization. However, there have been few reports of a suitable gene delivery system. In this study we used a cationic emulsion to immunize mice via the intranasal route with pCMV-S coding for Hepatitis B virus surface antigen (HBsAg). Complexing pCMV-S with a cationic emulsion dramatically enhanced HBsAg expression in both nasal tissue and lung, and was associated with increases in the levels of HBs-specific Abs in serum and mucosal fluids, of cytotoxic T lymphocytes (CTL) in the spleen and cervical and iliac lymph nodes, and of delayed-type hypersensitivity (DTH) against HBsAg. In contrast, very weak humoral and cellular immunities were observed following immunization with naked DNA. In support of these observations, a higher proliferative response of spleenocytes was detected in the group immunized with the emulsion/pCMV-S complex than in the group immunized with naked pCMV-S. These findings may facilitate development of an emulsion-mediated gene vaccination technique for use against intracellular pathogens that invade mucosal surfaces.

• BMB Reports
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• v.30 no.4
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• pp.269-273
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• 1997

Heptocvte-specific expression induced by Hepatitis B virus (HBV) enhancer 2-core gene promoter was examined in various hepatocyte and non-hepatocyte cell lines. using non-viral and retroviral vector systems in which chloramphenicol acetyltransferase (CAT) is used as a reporter. The non-viral plasmid containing the HBV enhancer 2-core promoter exhibited 22 and 66% of CAT activities in hepatoma cell lines. HepG2 and Hep3B, respectively when compared with CAT activity expressed by CMV promoter. The CAT activities, however. were found to be marginal in other tested hepatoma cell lines as well as mouse primary hepatocytes and non-hepatocytes. The HBV enhancer 2 located upstream the CMV promoter did not affect the CMV promoter activity nor provided hepatocyte-specific expression. Transfection of retroviral plasmid DNA containing the HBV enhancer 2-core promoter as an internal promoter exhibited high and specific CAT expression in HepG2 and Hep3B cell lines but the activity value was 5 to 10 fold lower than the non-viral plasmid with identical promoter. These results suggest that the usage of HBV enhancer 2-core promoter for liver specific expression is limited to certain vectors and hepatocyte cell lines.

• Neonatal Medicine
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• v.28 no.2
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• pp.83-88
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• 2021

Treatment guidelines for postnatal cytomegalovirus (pCMV) infection in preterm have not been established yet. Neutropenia, thrombocytopenia, hepatitis, colitis, and sepsis-like disease are among the clinical manifestations, which range from moderate to serious. We present a case of autopsy diagnosed as pCMV infection in a premature infant delivered at gestational age of 24 weeks and 5 days. On the 7th and 14th days of birth, urinary CMV polymerase chain reaction samples were negative, ruling out congenital CMV infection. However, autopsy examination revealed that the patient had disseminated pCMV infection. CMV inclusion bodies were found in the majority of tissues, including the lung, liver, pancreas, breast, kidney, and adrenal gland, but not the placenta. The thymus exhibited significant cortical atrophy and T-cell immunodeficiency, possibly induced by dexamethasone treatment for bronchopulmonary dysplasia or by pCMV infection itself. If dexamethasone treatment is extended or high doses are considered, it may be beneficial to test the CMV infection status to prevent aggravation of infection. This case demonstrates that, despite the low prevalence, pCMV infection should be considered a differential diagnosis in preterm if other conditions or etiology cannot justify clinical deterioration.

• Clinical and Experimental Pediatrics
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• v.53 no.1
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• pp.14-20
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• 2010

Cytomegalovirus (CMV) is currently the most common agent of congenital infection and the leading infectious cause of brain damage and hearing loss in children. Symptomatic congenital CMV infections usually result from maternal primary infection during early pregnancy. One half of symptomatic infants have cytomegalic inclusion disease (CID), which is characterized by involvement of multiple organs, in particular, the reticuloendothelial and central nervous system (CNS). Moreover, such involvement may or may not include ocular and auditory damage. Approximately 90% of infants with congenital infection are asymptomatic at birth. Preterm infants with perinatal CMV infection can have symptomatic diseases such as pneumonia, hepatitis, and thrombocytopenia. Microcephaly and abnormal neuroradiologic imaging are associated with a poor prognosis. Hearing loss may occur in both symptomatic and asymptomatic infants with congenital infection and may progress through childhood. Congenital infection is defined by the isolation of CMV from infants within the first 3 weeks of life. Ganciclovir therapy can be considered for infants with symptomatic congenital CMV infection involving the CNS. Pregnant women of seronegative state should be counseled on the importance of good hand washing and other control measures to prevent CMV infection. Heat treatment of infected breast milk at $72{^{\circ}C}$ for 5 seconds can eliminate CMV completely.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.1
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• pp.70-78
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• 2022

Purpose: Cholestasis resulting from cytomegalovirus (CMV)-induced hepatitis manifests in 40% of patients with a CMV infection. Ganciclovir treatment in children with CMV infections has proven to be highly effective. Until now, there are very few studies have identified predictive factors for liver biochemistry improvement after ganciclovir therapy. This study aimed to identify the predictors of liver biochemistry improvement in patients with CMV cholestasis after ganciclovir treatment. Methods: A retrospective cohort study was conducted using medical records from Dr. Sardjito General Hospital Yogyakarta, Indonesia from 2013 to 2018. CMV cholestasis was confirmed based on serum CMV IgG and IgM positivity and/or blood and urine CMV antigenemia positivity. Incomplete medical records and other etiologies for cholestasis, such as biliary atresia, choledochal cyst, metabolic diseases, and Alagille syndrome, were excluded. Patient age at cholestasis diagnosis and ganciclovir treatment, duration of CMV cholestasis, history of prematurity, central nervous system involvement, and nutritional status were analyzed and presented as an odds ratio (OR) with a 95% confidence interval (95% CI). Results: CMV cholestasis with ganciclovir therapy was found in 41 of 54 patients. Multivariate analysis showed that a shorter duration of CMV cholestasis (OR: 4.6, 95% CI: 1.00-21.07, p=0.04) was statistically significant for liver biochemistry improvement after 1 month of ganciclovir treatment. The remaining factors that were analyzed were not significant predictors of liver biochemistry improvement in patients with CMV cholestasis after ganciclovir treatment. Conclusion: A shorter duration of CMV cholestasis is the predictor of liver biochemistry improvement after 1 month gancyclovir treatment.

• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.276-282
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• 1998

Retinoids regulate a wide variety of biological processes such as cellular proliferation and differentiation in many cell types. They have also shown to stimulate replication of several viruses including human cytomegalovirus (CMV). Retinoid signalling pathway involves two distinct subfamilies of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs) that bind to specific retinoic acid response elements (RAREs) in the promoter regions of retinoid-target genes. Here, we characterized RAREs in the regulatory regions of the CMV and of the hepatitis B vi.us (HBV). The viral RAREs, i.e., CMV-RARE and HBV-RARE, are composed of two consensus RARE half-sites (A/GGGTCA) arranged as a direct repeat separated by 5-bp and 1-bp, respectively. The RAREs were activated by both RAR/RXR heterodimers and RXR homodimers in transient transfection experiments. We also found that COUP-TF$\alpha$ (chicken ovalbumin upstream promoter-transcription factor u) and COUP-TF$\beta$ repressed the retinoid response of the viral elements. Further we demonstrated that previously known retinoid antagonist, SRI 1330, repressed retinoid-induced transactivation of the CMV-RARE. These results implicate Vitamin A, it's nuclear receptors and COUP-TFs as important regulators of the CMV and HBV pathogenesis and the SRl1330 as potential negative modulator of such retinoid-dependent processes.

• Childhood Kidney Diseases
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• v.21 no.2
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• pp.75-80
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• 2017

Purpose: To investigate the frequency, presentation, management, and outcome of cytomegalovirus (CMV) infection in pediatric patients who underwent renal transplantation. Methods: We performed a retrospective chart review of 70 patients under the age of 18, who underwent renal transplantation between January 1990 and November 2014. A diagnosis of CMV infection was based on serology, molecular assays, antigenemia assays, and culture. CMV infection was defined as detection of virus and CMV disease was diagnosed when clinical signs and symptoms were present. Results: The number of patients with CMV infection was 18 (25.7% of renal transplant recipients). Twelve were male (66.7%), and the $mean{\pm}standard$ deviation (SD) age at infection was $13.3{\pm}3.9$ years. Median time of infection after renal transplantation was 4 months (range 1.0-31.0 months). Pretransplantation CMV status in the infected group was as follows: donor (D)+/recipient (R)+, 11 (61.1%); D+/R-, 7 (38.9%); D-/R+, 0; and D-/R- 0. Nine patients had CMV disease with fever, leukopenia, thrombocytopenia, or organ involvement such as enteritis, hepatitis, and pneumonitis. The age of disease occurrence was $13.1{\pm}3.9$ years and the median time to disease onset after renal transplantation was 8 months (range 1.0-31.0). Immunosuppressive agents were reduced or discontinued in 14 patients (77.8%), antiviral agents were used in 11 patients (61.1%), and all patients with CMV infection were controlled. Conclusions: A quarter of the patients had CMV infection about 4 months after renal transplantation. CMV infection was successfully treated with reduction of immunosuppressants or with antiviral agents.