MMP-7 Accurately Diagnoses Biliary Atresia

By Marilynn Larkin

October 14, 2019

NEW YORK (Reuters Health) - Matrix metalloproteinase-7 (MMP-7) shows "good accuracy" in diagnosing biliary atresia (BA) and "holds great promise" as a marker to differentiate BA from non-BA, a single-center validation study in Shanghai reveals.

Dr. Shan Zheng of Children's Hospital of Fudan University and colleagues enrolled 288 infants with neonatal obstructive jaundice in 2017 and 2018. For BA infants, the mean age was about 61 days and 43% were boys; the mean age in the non-BA group was 68 days and 75% were boys.

As reported online October 11 in Pediatrics, median serum MMP-7 levels were 38.89 ng/mL for the BA group and 4.4 ng/mL for the non-BA group.

The area under the receiver operating characteristic curve value was 0.9829 for MMP-7. At a cutoff value of 10.37 ng/mL, sensitivity was 95.19%; specificity, 93.07%; positive predictive value, 97.27%; and negative predictive value, 91.43%.

When MMP-7 was combined with g glutamyl transferase, the diagnostic accuracy was slightly, but not significantly, improved when compared with MMP-7 alone, with an area under the curve of 0.9880.

A decision curve analysis also showed potential for MMP-7 to be used for clinical applications, and a significant correlation was found with fibrosis stage, but not for inflammation grades, from liver biopsy.

The authors state, "The use of MMP-7 as a marker to differentiate BA from non-BA holds great promise. However, the protocol used to obtain and measure the blood samples requires further standardization before clinical application."

Dr. Ryan Fischer, a pediatric gastroenterologist and transplant hepatologist at Children's Mercy in Kansas City, agrees that MMP-7 is a promising diagnostic tool. "Serum MMP-7 levels are more elevated in infants with BA than those with liver conditions that are not BA," he said in an email to Reuters Health. "This is so important because the early identification of BA is associated with earlier treatment by Kasai portoenterostomy and more successful outcomes, including a delay - or possible avoidance - of liver transplant."

"Current diagnostic testing is invasive and imperfect," he noted, "so having an accurate serum-based marker of disease could allow earlier detection of BA and/or help avoid unnecessary testing in those not affected."

"MMP-7 levels may not be as useful in patients less than four weeks old," he said, "as levels tend to increase with time in patients with atresia. Thus, a patient with a non-atresia liver disease and a BA patient might have similar levels in the first few weeks of life. In patients more than one month old, however, the increasingly fibrotic BA patients tend to have much more serum MMP-7 and are more easily identified."

Future work should include "getting more data from patients with different liver diseases from different parts of the world and different ethnicities," he added. Variations in reference ranges for MMP-7 tests will also need to be addressed.

Pediatric gastroenterologist Dr. Jeremiah Levine of NYU Langone Health in New York City commented by email, "Although the sensitivity and specificity of an elevated MMP-7 was high, it was not 100%, and the most important thing one needs to be concerned about in the evaluation of a child with cholestasis is to ensure that no patient is missed."

"The authors' previous study (noted in the paper) demonstrated that 14% of 602 patients with cholestasis were found to be non-BA following invasive diagnostic procedures," he told Reuters Health. "I am not sure if the serum levels will be sensitive and specific enough to prevent the need (for invasive procedures) for this group."

"Additionally," he said, "MMP-7 is associated with fibrosis, so I wonder whether in other neonatal non-BA liver diseases that have fibrosis as a prominent feature, the serum MMP-7 level will be as useful in differentiating those disorders from BA."

Dr. Zheng did not respond to requests for a comment.


Pediatrics 2019.