CMV marker in bile duct cells tied to worse biliary atresia outcomes
Children with marker had poorer results after Kasai surgery
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Children with biliary atresia who had evidence of active cytomegalovirus (CMV) infection involving bile duct cells in the liver had signs of more severe liver disease and worse outcomes after Kasai surgery, according to a new study.
“These findings underscore the clinical relevance of timely initiation of antiviral treatment (AVT) in BA [biliary atresia] patients with CMV infection,” the researchers wrote.
They noted, however, that the study included a small number of patients, and other factors — most notably differences in age at surgery — may have affected the outcomes. The study also did not directly test whether antiviral treatment would improve outcomes. As such, further studies are needed to better understand the role of this infection in biliary atresia.
CMV’s role in biliary atresia remains unclear
The study, “Hepatic CMV-IE expression and distribution further defines the aetiological and prognostic subtypes of biliary atresia,” was published in the Journal of Pediatric Surgery.
Biliary atresia is a disorder marked by blockage or complete absence of the bile ducts, a series of tubes that carry the digestive fluid bile from the liver to the intestines. As a result, bile cannot flow properly, so it builds up in the liver and causes damage.
The first-line treatment is Kasai surgery, a procedure that creates a new pathway for bile to drain from the liver into the intestines.
The causes of biliary atresia are not well understood. Some studies have suggested that viral infections before or immediately after birth may play a role in biliary atresia risk. One such virus is CMV, which often does not cause noticeable symptoms, but infection before birth can cause developmental problems in some babies.
CMV can infect multiple types of liver cells, including hepatocytes and cholangiocytes, or bile duct cells, and “has been closely associated with the disease progression and prognosis of BA,” the researchers wrote.
Now, a team of scientists in China analyzed where CMV was detected in liver tissues from 102 children with biliary atresia and evaluated whether this was associated with outcomes after Kasai surgery. They specifically looked at CMV immediate-early protein (CMV-IE), a marker of active viral activity in tissue.
Liver tissue testing found CMV marker in bile duct cells
Liver tissue used to detect CMV-IE was collected during the Kasai procedure. None of the children received antiviral treatment around the time of surgery. All were followed for at least one year after surgery.
Liver tissue analyses showed that most of the children, 61.8%, were negative for CMV-IE. Among the 39 children testing positive for this infection marker, 30, or 76.9%, had CMV-IE detected outside bile duct regions, while the remaining nine, or 23.1%, had CMV-IE involving bile duct cells.
Statistical tests revealed that the nine children with evidence of CMV infection involving bile duct cells had signs of more severe liver disease and worse outcomes, compared with those who were CMV-IE negative or had CMV-IE detected only outside bile duct regions.
At the time of surgery, children with CMV-IE involving bile duct cells had significantly higher blood levels of markers of liver damage than the other two groups of children. They were also significantly more likely to have severe liver scarring, or fibrosis, than children who had CMV-IE detected only outside bile duct regions or those who were CMV-IE negative (88.9% vs. 43.3% vs. 25.4%, respectively).
After surgery, the group with CMV-IE involving bile duct cells was significantly less likely to have resolution of jaundice, or yellowing of the skin and eyes, within three months. They also had the highest rate of cholangitis, or bile duct inflammation, within six months.
Bile duct CMV marker tied to lower native liver survival
Further analyses showed that children with CMV-IE involving bile duct cells were significantly less likely to keep their native liver — meaning their own liver, without a transplant — at two years after Kasai surgery than children with CMV-IE detected only outside bile duct regions and those who were CMV-IE negative (33.3% vs. 63% vs. 63%, respectively).
These findings suggest that CMV-IE involving bile duct cells may be a marker of more severe biliary atresia. However, the team stressed that the children with CMV-IE involving bile duct cells were significantly older than those in the other two groups at the time of surgery (median of 71 vs. 57 vs. 51 days).
Because an earlier age at Kasai surgery is strongly predictive of better outcomes after the procedure, this difference in age “may have contributed, at least in part, to their poorer [post-surgery] outcomes,” the researchers wrote. They called for additional studies with larger sample sizes to further explore the prognostic value of CMV-IE patterns in biliary atresia.
Of note, many of the children also had results available from blood testing for CMV-IgM antibodies, serum or urine testing for CMV DNA, or both. Results from these tests often did not line up with data from liver tissue analyses. For example, about one-third of children who tested negative for CMV-IgM antibodies or CMV DNA still had CMV-IE detected in liver tissue.
“These findings … support the notion that [blood] testing alone may not reliably indicate the presence of viral activity in target organs,” the researchers wrote, noting that serological antibody testing in newborns is especially prone to both false negatives and false positives. This will be an important consideration for future research into CMV’s role in BA, the researchers noted.
