In this single-center retrospective study with 19 patients, MMP-7 and GGT values were compared in children who were diagnosed with Parenteral Nutrition-Associated Liver Disease (PNALD, n=15) and Biliary atresia (n=4). Key findings:
Median MMP-7 values for PNALD patients 37.8 ng/mL was much lower than MMP-7 values for biliary atresia 112.3 ng/mL.
GGT values were not statistically significantly different 116 for PNALD vs 248 for biliary atresia
In this cohort, a MMP-7 threshold of 52.8 ng/mL had a sensitivity of 100% and specificity of 93.5% for biliary atresia.
My take: MMP-7 values reduce diagnostic uncertainty between PNALD and biliary atresia. However, there are infrequent cases of biliary atresia with lower values of MMP-7.
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New Test Expedites the Diagnosis of Biliary Atresia
A groundbreaking test developed at Cincinnati Children’s can expedite a diagnosis of biliary atresia (BA), helping physicians decide quickly whether to perform a liver biopsy followed by an operative cholangiogram, the definitive test for BA. The test quantifies the concentration of MMP-7 (matrix metalloproteinase-7), a serum protein that researchers at Cincinnati Children’s discovered in 2017 is a biomarker of BA.
Physicians can order the MMP-7 assay by submitting a requisition form. Test results are available within 48 hours, and a pediatric hepatologist is always available for consultation regarding the interpretation of test results.
As noted by my previous blog (New Way to Diagnose Biliary Atresia), I am enthusiastic about the development of MMP-7 (Serum Matrix Metalloproteinase-7) as a biomarker for biliary atresia.
A new study (Wu J-F , Jeng Y-M, Chen H-L, Ni Y-H, Hsu H-Y, Chang M-H. Quantification of serum matrix metallopeptide 7 levels may assist the diagnosis and outcome prediction for biliary atresia. J Pediatr. 2019;208:30–7) and associated editorial provide additional data and nuance.
“Wu et … studied 100 cholestatic infants presenting consecutively to their institution over a 10-year period, including 36 eventually diagnosed with biliary atresia. Median serum MMP-7 levels were significantly higher in biliary atresia at the time of diagnosis, with an optimal serum MMP-7 level of >1.43 ng/mL for predicting biliary atresia. In comparison, similarly high MMP-7 levels were found in only 1 infant who was cholestatic without biliary atresia.”
“The authors found that serum MMP-7 levels were significantly lower in the 14 infants ≤30 days old diagnosed with biliary atresia, compared with the 22 infants >30 days old at diagnosis. In some cases, serum MMP-7 levels in younger infants with biliary atresia overlapped with those from infants with other liver diseases, such as neonatal hepatitis.”
After Kasai portoenterostomy: “Serum MMP-7 levels were significantly higher 6 months post-Kasai portoenterostomy in infants who later required liver transplant, with a serum MMP-7 level of >10.30 mg/dL optimally predicting transplant 3-4 years after Kasai portoenterostomy … serum MMP-7 levels are still high even in patients who do not need liver transplant.”
The authors “highlight 1 complication with using serum MMP-7 levels: values can vary widely among different enzyme-linked immunosorbent assay kits used.”
Case report: Recently, our group consulted on a 3 week old infant (ex34 week) who weighed 2.8 kg and had cholestasis. In addition, he had a GGT in the 400s and an ultrasound notable for a “small” gallbladder. Due to the patient’s small size, he underwent a HIDA (no excretion). The GGT was actually improving but the clinical situation was concerning for biliary atresia.
Instead of arranging a liver biopsy, we were able to perform a MMP-7 (Serum Matrix Metalloproteinase-7) assay which will be commercially available soon. The result, which returned in 48 hours, indicated that the child had a >95% likelihood of biliary atresia. Subsequently, this infant is recovering from a hepatoportoenterostomy. No liver biopsy was needed prior to surgery.
My take: The MMP-7 assay is a remarkable test which is going to rapidly change the approach to infants with cholestasis. I expect that this test will be ordered along with a serum alpha-one antitrypsin phenotype and an ultrasound. In those with persistent cholestasis with negative initial testing, it is likely that, in the majority, a genetic cholestasis panel would be pursued rather than a liver biopsy.