Among children with cystic fibrosis (CF) liver disease (CFLD), those with nodular liver (NOD) have more liver-related complications than those without, according to study findings published in the Journal of Cystic Fibrosis.
The Prediction by Ultrasound of the Risk of Hepatic Cirrhosis (PUSH) study enrolled children (N=166) aged 3 to 12 years with CF between 2010 and 2013. In this 9-year longitudinal study, participants were evaluated by ultrasound for outcomes at years 2, 4, 6, 8, and 9. Risk for liver-related events were evaluated on the basis of NOD status. Children without NOD at baseline and who did not develop NOD were used as the comparator group.
Among the NOD cohort, 24 had NOD at baseline, 15 presented with NOD at year 2, 13 at year 4, and 4 at year 6.
The children with NOD (n=54) and without NOD (n=112) had a mean age of 10.9±3.0 and 8.4±3.1 years (P <.0001); 61% and 49% were male; and 96.3% and 94.6% were White, respectively.
At baseline, the NOD group vs the group without NOD had lower platelet levels and white blood cell counts and higher total bilirubin, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase (all P £.013). In addition, NOD was associated with greater liver stiffness, fibrosis index based on 4 factors (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and larger spleen Z-score (all P <.0001).
Six patients in the NOD group had esophageal varices, 2 of whom had bleeding at 11.1 and 12.9 years of age. The cumulative incidence rate of esophageal varices at 10 years was 20%. Of the 6 patients with esophageal varices, 4 had NOD at baseline and the other 2 converted to NOD at year 2. Two patients underwent liver transplant.
No liver events were observed among the group without NOD.
During the follow-up, the NOD cohort vs the group without NOD had significantly greater increases in spleen size Z-score (P <.0001) and APRI (P =.0006) and decreases in platelet levels (P =.018). No longitudinal group differences were observed for albumin, BMI Z-scores, or forced expiratory volume in 1 second.
During the follow-up, 59.6% of the NOD group and 63.6% of the group without NOD received CF transmembrane regulator modulation therapy (P =.62). Similarly, the proportion of patients without CF-related diabetes did not differ on the basis of NOD status (P =.6643).
The major limitation of this study was that liver biopsies were not collected.
The study authors concluded, “NOD is an early marker for advanced liver disease, characterized by preserved synthetic function, nutritional status, and pulmonary function that cannot be distinguished from NL. NOD is associated with increased liver stiffness, spleen size, APRI and FIB-4, as well as a more rapid decline in platelet count, suggesting emerging clinically evident portal hypertension.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Leung DH, Ye W, Schwarzenberg SJ, et al. Long-term follow-up and liver outcomes in children with cystic fibrosis and nodular liver on ultrasound in a multi-center study. J Cyst Fibros. Published online August 16, 2022. doi:10.1016/j.jcf.2022.07.017