High frequency of Human Cytomegalovirus DNA in the Liver of Infants with Extrahepatic Neonatal Cholestasis

Tommaso, Adriana María Alves De; Andrade, Paula Durante; Costa, Sandra Cecı́lia Botelho; Escanhoela, C.A.F.; Hessel, Gabriel

doi:10.1186/1471-2334-5-108

Cited by 49 publications

(59 citation statements)

References 32 publications

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“…Lurie et al [35] , after studying four fatal cases of NIHC from CMV, described the presence of cytomegalic cells in the liver from two of them. None were detected in the present study or observed in cases of extrahepatic cholestasis (EHC) [36][37][38] . In CMV hepatitis following orthotopic liver transplantation (immunosuppressed patients), demonstration of cytomegalic inclusion bodies in hematoxylin and eosin sections is sufficient for a diagnosis of CMV hepatitis [39] .…”

Section: Discussionmentioning

confidence: 56%

Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

Bellomo-Brandão¹,

Andrade²,

Costa³

et al. 2009

WJG

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AIM:To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods. METHODS:The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's files and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specific positive predictive value, negative predictive value, and accuracy. RESULTS:T he fre que nc ie s o f po s i t ive re s u l t s were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%), and PCR, 6/77 (8%). Only one patient had positive immunohistochemical findings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity, 88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%. CONCLUSION:The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low.

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Section: Discussionmentioning

confidence: 56%

Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

Bellomo-Brandão¹,

Andrade²,

Costa³

et al. 2009

WJG

Self Cite

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“…8,10,18 Although no unequivocal link has been established between BA and CMV infection, there appears to be a fairly strong correlation between the two, as demonstrated by our study. CMV is a slow replicating virus from the herpes family, infecting only as many as 1% of all neonates in developed countries, 9 but demonstrating up to 90% IgG-positivity in developing countries. 19 Only 5 -10% of infected infants have typical CMV inclusion disease with symptoms of hepatosplenomegaly, jaundice and petechiae; a further 5% having subclinical disease.…”

Section: Discussionmentioning

confidence: 99%

“…15 Although there appears to be a correlation between CMV infection and BA, the significance must still be determined due to the small cohorts studied thus far. 4,5,7,[9][10][11]16,17 Human CMV infection is a strong candidate, being cholestatic in its own right. 5,9 It has also been associated with intrahepatic bile duct destruction and ductal paucity, indicating a possible role in the pathogenesis and progression of extrahepatic BA.…”

Section: Discussionmentioning

confidence: 99%

“…4,5,7,[9][10][11]16,17 Human CMV infection is a strong candidate, being cholestatic in its own right. 5,9 It has also been associated with intrahepatic bile duct destruction and ductal paucity, indicating a possible role in the pathogenesis and progression of extrahepatic BA. 7,8 In addition, when related to BA, CMV-IgM-positive patients appear to have greater liver damage, consequently affecting outcome deleteriously.…”

Section: Discussionmentioning

confidence: 99%

“…1,9,13,16 Serology, CMV quantitative polymerase chain reaction (qPCR), immunohistochemistry and histology have been unable to confirm a possible role of CMV in BA aetiology. De Tomasso et al 9 describe a low accuracy of serological tests for detecting active CMV infection, with no correlation between the CMV-positive qPCR and histopathological changes reported by others. 1,13,16 Our study, however, reinforces a probable correlation.…”

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confidence: 99%

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Problems related to CMV infection and biliary atresia

2012

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Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells

et al. 2012

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Biliary atresia (BA) is a progressive, inflammatory cholangiopathy that culminates in fibrosis of extrahepatic and intrahepatic bile ducts. A leading theory on the pathogenesis of BA is that the bile duct damage is initiated by a virus infection, followed by a bile duct-targeted autoimmune response. One mechanism of autoimmunity entails diminished number or function of regulatory T cells (Tregs). The aim of this study was to identify potential virus-specific liver T cells from infants with BA at the time of diagnosis, implicating the virus involved in early bile duct damage. A subaim was to determine if presence of virus infection was associated with quantitative changes in Tregs. Results: Liver T cells from BA and control patients were cultured with antigen presenting cells in the presence of a variety of viral or control proteins. 56% of BA patients had significant increases in IFN-γ-producing liver T cells in response to cytomegalovirus (CMV), compared to minimal BA responses to other viruses or the control group CMV response. In addition, a positive correlation between BA plasma CMV IgM and liver T cell CMV reactivity was identified. Investigation of peripheral blood Tregs revealed significant deficits in Tregs frequencies in BA compared to controls, with marked deficits in those BA patients who were positive for CMV. Conclusions: Liver T cell responses to CMV were identified in the majority of BA patients at diagnosis, suggesting perinatal CMV infection as a plausible initiator of bile duct damage. Deficiency of Tregs in BA implies decreased inhibition of inflammation and autoreactivity, potentially allowing for exaggerated bile duct injury.

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High frequency of Human Cytomegalovirus DNA in the Liver of Infants with Extrahepatic Neonatal Cholestasis

Cited by 49 publications

References 32 publications

Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

Problems related to CMV infection and biliary atresia

Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells

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