Relationship between prognosis of biliary atresia and infection of cytomegalovirus

Abstract

There is a strong correlation between cytomegalovirus infection and a lower rate of jaundice disappearance, also a higher post-operational reflux cholangitis. Liver fibrosis seems to be more severe in biliary atresia patients with cytomegalovirus infection.

Problems related to CMV infection and biliary atresia

“…7,8 In addition, when related to BA, CMV-IgM-positive patients appear to have greater liver damage, consequently affecting outcome deleteriously. 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.…”

“…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.…”

“…This raises the possibility that CMV infection might not only be a causative factor, but may promote ongoing biliary tree sclerosis. 10,18 The presence of co-morbidities such as HIV raises interesting possibilities in the antigen-antibody hypothesis of BA aetiology. This is of particular interest in areas of high HIV prevalence, such as sub-Saharan Africa, and is probably explained by the fact that some non-BA patients with neonatal hepatitis on biopsy were subsequently shown to be HIV-related.…”

Cytomegalovirus in biliary atresia: coincidental or causal?

“…A study from China reports a strong association between CMV and lower rate of jaundice disappearance following operation. They also found increased fibrosis as we found in our patients 8 . However a study from Canada, with CMV DNA analysis on bile duct biopsy specimens showed negative results ruling out any association of CMV involved in the pathogenesis of EHBA 9 .…”

Low doses of CMV induce autoimmune-mediated and inflammatory responses in bile duct epithelia of regulatory T cell-depleted neonatal mice

“…[15][16][17] Recently, it was reported that 56% of BA patients had significantly higher liver T-cell numbers in response to CMV and that a positive correlation exists between plasma anti-CMV IgM and CMV-specific T cells in the liver of BA patients. [17][18][19][20][21] Regulatory T cells (Tregs) are defined by expression of the surface markers CD4 and CD25 and the transcription factor Foxp3. 22 Tregs represent a small percentage of CD4 þ T cells and are indispensable for the maintenance of peripheral tolerance and the prevention of autoimmune diseases.…”