Biliary atresia causes
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
There have been many theories about etiopathogenesis such as Reovirus 3 infection, congenital malformation, congenital CMV infection, autoimmune theory. This means that the etiology and pathogenesis of biliary atresia are largely unknown.
Causes
Biliary atresia does not have a clear identified cause. It was previously thought to be idiopathic, a destructive inflammatory process leaving fibrotic remnants at the porta hepatis. It is now thought it may be secondary to viral infections or an autoimmune-induced injury in some cases. The viruses thought to be involved are:
- Reovirus,
- Rotavirus,
- Cytomegalovirus (CMV)[1][2]
- The highest association of a viral infection with biliary atresia is with CMV. There may be an inability to identify the virus because of a short timeframe to detect it, which leads to uncertainty in association. The viral infection of cholangiocytes may predispose to an aberrant autoimmune response, cascading to progressive biliary injury and cirrhosis.
Genetic cause
Through a genome-wide study, an association between biliary atresia and the ADD3 gene was detected in Chinese populations and confirmed in Thai populations. Anther possible association with the deletion of the GPC1 gene has been reported, which encodes a glypican 1-a heparan sulfate proteoglycan.[3]
Environmental cause
Aflatoxin B1 exposure, and to a lesser extent aflatoxin B2 exposure during late pregnancy may cause biliary atresia. Maternal detoxification ability protects the fetus during intrauterine life, but it struggles with the aflatoxin in its blood and liver after birth, causing cholangitis in the baby. [4]
References
- ↑ Brindley SM, Lanham AM, Karrer FM, Tucker RM, Fontenot AP, Mack CL (2012). "Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells". Hepatology. 55 (4): 1130–8. doi:10.1002/hep.24807. PMC 3319336. PMID 22105891.
- ↑ Xu Y, Yu J, Zhang R, Yin Y, Ye J, Tan L; et al. (2012). "The perinatal infection of cytomegalovirus is an important etiology for biliary atresia in China". Clin Pediatr (Phila). 51 (2): 109–13. doi:10.1177/0009922811406264. PMID 22144720.
- ↑ Cui S, Leyva-Vega M, Tsai EA, EauClaire SF, Glessner JT, Hakonarson H; et al. (2013). "Evidence from human and zebrafish that GPC1 is a biliary atresia susceptibility gene". Gastroenterology. 144 (5): 1107–1115.e3. doi:10.1053/j.gastro.2013.01.022. PMC 3736559. PMID 23336978.
- ↑ https://scholar.cu.edu.eg/?q=magdkotb/files/aflatoxins_in_biliary_atresia.pdf