Most babies with biliary atresia test positive for rotavirus antibodies
Common childhood virus may help drive the rare liver disease, study suggests
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Most infants with the rare liver disease biliary atresia (BA) show signs of a previous rotavirus infection, suggesting the common childhood virus may play a role in the development of the condition.
A new study from Japan found that more than 70% of babies with the disease tested positive for rotavirus antibodies, compared to about 3% of healthy infants — a difference that adds weight to the theory that viral infections play a role in damaging the liver’s bile ducts.
While the exact cause of biliary atresia remains unknown, these findings provide evidence that rotavirus is linked to the disease in humans. Researchers believe the discovery could eventually lead to better screening or even preventive strategies for at-risk newborns.
Further multicenter studies that follow infants over time are required to “elucidate the causal role” of rotavirus infection in biliary atresia development, researchers noted, emphasizing that while the association is strong, more work is needed to prove the virus actually causes the damage.
The study, “Association of Rotavirus Infection With Biliary Atresia: A Retrospective Comparative Analysis of Virus-Specific Antibodies,” was published in the Journal of Medical Virology.
The mechanics of biliary atresia
In biliary atresia, the bile ducts — a series of tubes that carry the digestive fluid bile out of the liver to the intestines — are blocked or entirely absent. This leads bile to build up to toxic levels in the liver, which drives liver damage.
The causes of biliary atresia are unclear. Various studies have suggested that genetic variations, abnormal immune responses, or problems during fetal development may play a role.
In addition, “infections with rotavirus (RV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) have long been implicated in the [development] of BA,” the researchers wrote.
Rotavirus infection primarily affects infants, often with mild or no symptoms, and young children, in whom it causes intense diarrhea and vomiting. Animal studies have indicated that rotavirus may contribute to biliary atresia development.
However, “evidence supporting [a similar] role for RV in humans remains limited, and the contribution of the virus to disease [development] has yet to be conclusively established,” the researchers wrote.
When the body is infected with a virus, the immune system produces antibodies that target the virus to fight the infection. As such, if a person tests positive for antibodies targeting a particular virus, it’s a good indication that the individual has been infected with that virus.
In this study, the researchers tested for anti-rotavirus antibodies in 17 babies with biliary atresia and 30 infants without the disease or any notable signs of digestive upset. None of the babies had been vaccinated against rotavirus, which would also have activated the immune system to trigger antibody production.
The biliary group had a significantly higher proportion of girls than the non-biliary atresia group (82.4% vs. 40%).
Results showed that 12 babies with biliary atresia (70.6%) tested positive for rotavirus antibodies, whereas only one of the children without biliary atresia (3.4%) tested positive. This difference was statistically significant.
Levels of rotavirus antibodies were also significantly higher in the biliary atresia group.
Further analyses showed that infants with biliary atresia who were negative for rotavirus antibodies were significantly younger at symptom onset than those who tested positive (median of four days vs. 63.5 days, or about two months).
The researchers also tested the infants for antibodies against two other common childhood viruses previously linked to biliary atresia: CMV and EBV. However, results were negative in most infants, with no difference between those with and without biliary atresia.
“These findings suggest that RV, rather than EBV or CMV, is involved in BA [development],” the researchers wrote, noting, however, that “the role of the RV remains unclear, as previous studies have reported no change in BA incidence after RV vaccination.”
The researchers called for more studies to clarify the role of rotavirus in biliary atresia and other contributing factors. “Future studies may need to … follow infants suspected of having BA, monitor [anti-RV] antibody [levels] over time, test for RV … in stool, and closely observe clinical symptoms,” they concluded.