Two recent studies provide more information on biliary atresia (BA) biomarkers.

• OG Behairy et al. JPGN 2020; 70: 344-9.
• S Shamkar et al. JPGN 2020; 70: 350-5.

Behairy et al report on the use of serum IL-33 in a cohort of 90 infants, 30 with BA, 30 with cholestasis due to other causes, and 30 healthy infants.

• Using a cut-off of 20.8 pg/mL, IL-33 had a specificity of 95% and sensitivity of 96.7% for identifying BA.
• Interestingly, the test performed better in those with advanced fibrosis.  The mean value of IL-33 in those with grade 3/6 was 88.2 compared to 37.2 for 1/6 and 70.9 for 2/6. In comparison, the children with cholestasis due to other liver disease had a level of 18.5 for those with 3/6 fibrosis

The authors note in a prior study that IL-33 was higher in BA infants than those with a choledochal cyst.

While this is a small study, I disagree with the editorial (pg 278-9) which largely discounted the potential role of IL-33.  “IL-33 is elevated with many other diseases (bronchopulmonary dysplasia, asthma, allergy, and more) It, therefore, cannot easily be used as a highly specific marker for fibrosis. Furthermore, the use of IL-33 as a prognostic marker, is from a clinical point of view not of great importance, as follow-up clinical decisions are generally made based on patients’ clinical course.”

Shankar et al provide data on GGT values in BA (n=113 infants).

These infants underwent Kasai procedure at a median of 61 days

• 12.3% had normal (<200) GGT values.
• Those with normal GGT had worse outcomes: earlier need for liver transplantation (14 vs 20 months) and poorer transplant survival.
• 9/14 (64%) with normal GGT and 53/99 (53.5%) of elevated GGT underwent liver transplantation

The authors note that decreased levels of GGT has been associated with reduced glutathione metabolism which could impari adaptive response to oxidative stress, leading to further hepatocyte injury.

My take: In my experience, I have had very few BA patients with GGT values <200 (lower than 10%).  The development of other biomarkers like MMP-7 and IL-33 increase the likelihood that BA will be recognized sooner and if elevated, could obviate the need for a liver biopsy prior to operative cholangiogram.  Nevertheless, practitioners cannot wholly rely on any the current biomarkers.

Related blog posts:

• More data, More Nuance with MMP-7
• Blood Test is Better Than a Liver Biopsy for Bilary Atresia
• Predicting Future Liver Disease with GGT Values in Biliary Atresia
• Will We Still Need a Liver Biopsy to Diagnose Biliary Atresia in a Few Years?
• Helpful Review on Biliary Atresia | gutsandgrowth
• Newborn bilirubin measurements for biliary atresia
• Neonatal cholestasis for neonatologists
• Guideline links for TEF and Infant Cholestasis
• Neonatal Cholestasis Lecture
• Diagnosing biliary atresia earlier | gutsandgrowth

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