Total Bilirubin, MMP-7, and TBA Show Promise for Predicting Liver Survival in Biliary Atresia

Ahmad Anouti, MD
Credit: UT Southwestern

Analysis of more than 2 dozen studies in biliary atresia provides an overview of serum values as prognostic indicators for native liver survival following hepatic portoenterostomy.

Presented at the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) 2024 annual meeting, results detail the prognostic value of several serum values, including total bilirubin (TB), ALT, GGT, MMP-7, and total bile acids (TBA).¹

“My goal was to create a uniform algorithm we can say, as clinicians can follow using simple to use serum markers that are either old or new to prognosticate at different time points” explained Ahmad Anouti, MD, of the Digestive and Liver Disease, The University of Texas Southwestern Medical Center, in an interview with HCPLive.

Despite being the most common treatment for biliary atresia, which is the leading cause of pediatric liver transplantation, most patients will still go on to require transplant, with a considerable degree of variation observed for time until transplant among this group. According to an October 2023 study by Anouti, 2754 biliary atresia waitlist additions and 2206 biliary atresia liver transplants were recorded within the UNOS database from January 2010 through December 2021.^2,3

To better inform management strategies, Anouti and fellow investigators designed a systemic review and meta-analysis to elucidate associations between serum values and native liver survival among patients with biliary atresia. The study leveraged data from the PubMed, MEDLINE, SCOPUS, and EMBASE databases published from 1946 through December 2023 examining the prognostic values of serum values for biliary atresia after hepatic portoenterostomy.¹

The specific values of interest for the study were TB, ALT, GGT, MMP-7, and TBA. For the purpose of analysis, non-function hepatic portoenterostomy was defined as persistent jaundice, cirrhosis, liver transplantation, or death. Investigators pointed out associations between pooled serum variables with native liver survival were calculated as hazard ratios (HRs) and odds ratios (ORs) using the inverse variance weighting method.¹

From their search, a total of 30 studies were identified for inclusion. From these studies, investigators obtained data from 4399 BA patients, including 2073 with successful hepatic portoenterostomy and 1793 with non-functioning hepatic portoenterostomy. Investigators noted the mean time to hepatic portoenterostomy for the success group was 63.3 (SD, 0.18) days compared with 69.5 (SD, 0.20) days in the failure group (P <.001).¹

Results indicated TB levels were significantly greater among the non-functioning group (P < .001). ALT and GGT levels were significantly reduced in the success group at both 1 to 3 months and beyond 5 years post-hepatic portoenterostomy (P <.001).¹

Investigators spotlighted a single study suggesting non-liver-specific survival decreased when MMP-7 levels exceeded 10.3 ng/mL (HR, 4.29; 95% CI, 1.12 to 16.52). Investigators also highlighted results from 2 studies indicating serum TBA levels in the success group (27.55 μmol/L; 95% CI, 20.35 to 34.75) were significantly lower than in the non-functioning group (69 μmol/L; 95% CI, 56.26 to 81.74) more than 5 years post-hepatic portoenterostomy (P <.001).¹

“For me, what's the most fascinating thing is total bile acids, which are relatively new and we only found in 2 studies, showed at 1 year and at greater than five years promise in prognosticating kids. So that's quite interesting,” Anouti added.

References:

1. Anouti A, Dahshi H, Cotter T, et al. SERUM VALUES IN BILIARY ATRESIA PATIENTS AS INDICATORS FOR NATIVE LIVER SURVIVAL: A SYSTEMATIC REVIEW AND META-ANALYSIS. Presented at NASPHGAN 2024 in Hollywood, Florida, from November 7 – November 9, 2024.
2. Antala S, Taylor SA. Biliary Atresia in Children: Update on Disease Mechanism, Therapies, and Patient Outcomes. Clin Liver Dis. 2022;26(3):341-354. doi:10.1016/j.cld.2022.03.001
3. Anouti A, Patel MS, VanWagner LB, et al. Biliary atresia and liver transplantation in the United States: A contemporary analysis. Liver Int. 2023;43(10):2198-2209. doi:10.1111/liv.15689