Liver Stiffness Measurement Predicts Long-Term Outcomes In Pediatric Biliary Atresia
FROM GASTROENTEROLOGY
according to investigators.
These findings suggest that LSM may serve as a noninvasive tool for risk stratification and treatment planning in this population, reported lead author Jean P. Molleston, MD, of Indiana University School of Medicine, Indianapolis, and colleagues.
“Biliary atresia is frequently complicated by hepatic fibrosis with progression to cirrhosis and portal hypertension manifested by ascites, hepatopulmonary syndrome, and variceal bleeding,” the investigators wrote in Gastroenterology. “The ability to predict these outcomes can inform clinical decision-making.”
To this end, VCTE has been gaining increasing support in the pediatric setting.
“Advantages of VCTE over liver biopsy include convenience, cost, sampling bias, and risk,” the investigators wrote. “VCTE potentially allows (1) fibrosis estimation, (2) prediction of portal hypertension complications/survival, and (3) ability to noninvasively monitor liver stiffness as a fibrosis surrogate.”
The present multicenter study aimed to gauge the prognostic utility of VCTE among 254 patients, aged 21 years or younger, with biliary atresia. All patients had a valid baseline LSM, plus longitudinal clinical and laboratory data drawn from studies by the Childhood Liver Disease Research Network (ChiLDReN). Liver stiffness was assessed noninvasively with FibroScan devices, adhering to protocols that required at least 10 valid measurements and a variability of less than 30%.
The primary outcomes were survival with native liver (SNL), defined as the time to liver transplantation or death, and a composite measure of liver-related events, including the first occurrence of transplantation, death, ascites, variceal bleeding, or hepatopulmonary syndrome. Secondary outcomes focused on the trajectory of platelet decline, a marker of disease progression. The study also explored the relationship between baseline LSM and conventional biomarkers, including platelet count, albumin, and bilirubin.
LSM was a strong predictor of long-term outcomes. Specifically, Kaplan-Meier analysis showed significant differences in 5-year SNL across LSM strata (P < .001). Children with LSM values less than 10 kPa had excellent 5-year SNL rates (LSM 10 to < 15 kPa, 88.9%; 95% CI, 75.1-95.3%), while those with LSM of at least 15 kPa exhibited substantially lower 5-year SNL (58.9%; 95% CI, 46.0-69.7%).
Similarly, event-free survival (EFS) rates declined as LSM values increased (P < .001). Participants with LSM less than 10 kPa had a 5-year EFS rate of 92.2% versus with 61.2% for those with LSM of at least 15 kPa.
LSM also predicted platelet decline. For every twofold increase in baseline LSM, platelet counts declined by an additional 4,000/mm3 per year (P < .001). This association was illustrated through predicted trajectories for participants with LSM values of 4, 7, 12, 18, and 42 kPa, corresponding to different percentiles of disease severity.
Cox proportional hazards analysis indicated that a two-fold increase in LSM was associated with a hazard ratio of 3.3 (P < .001) for liver transplant or death. While LSM had good discrimination on its own (C statistic = 0.83), it did not significantly improve predictive accuracy when added to models based on platelet count, albumin, and bilirubin.
“This noninvasive measurement could potentially be used to predict natural history, stratify patients for clinical trials, plan interventions, and provide anticipatory guidance,” Molleston and colleagues concluded. This study was supported by grants from the National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; Childhood Liver Disease Research Network; and others. The investigators disclosed no conflicts of interest.