Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis Liver Disease (CFLD PUSH)

Cystic fibrosis is an inherited condition in which cell secretions are thick and sticky, instead of thin and slippery. The secretions obstruct passageways and ducts, leading to severe internal damage. Patients with cystic fibrosis sometimes develop advanced liver disease (CFLD). Hepatic cirrhosis can occur with CFLD, as a result of the inflammation and scarring caused by clogged bile ducts.

The Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis Liver Disease (CFLD PUSH) study was a prospective longitudinal study that aimed to determine the utility of abdominal ultrasound to predict the development of cirrhosis in patients with cystic fibrosis as indicated by a nodular liver on ultrasound. Participants underwent abdominal ultrasound at enrollment and based on the outcome, were placed in one of four groups. Within a 10-year period, participants underwent other specimen collection procedures in addition to abdominal ultrasound. This study also monitored the effects of cystic fibrosis on associated pulmonary and nutritional issues.

The objective of the CFLD PUSH study was to determine the usefulness of abdominal ultrasound when attempting to predict the development of cirrhosis in participants with cystic fibrosis.

The primary outcome measure was development of cirrhosis as indicated by the development of a nodular ultrasound during a six-year period of monitoring. The secondary outcome measures were effects on associated pulmonary and nutritional issues.

Inclusion criteria:

· Age 3-12 years old

· Diagnosed with cystic fibrosis and pancreatic insufficiency

· Enrolled in the CFF Registry Study or Toronto CF Registry

Exclusion criteria:

· Had cirrhosis

· Presence of Burkholderia cepacian

· Short bowel syndrome

· Had serious disease that would prevent participation

Of the 764 participants enrolled at baseline, 722 were assigned a final ultrasound (US) grade: 592 normal US pattern (NL), 65 heterogeneous increased echogenicity of the liver (HTG), 41 nodular pattern (NOD), and 24 homogeneous increased echogenicity of the liver (HMG). There were 62 HTG that were matched to 125 NL and followed for up to 10 years. At 6 years, those with a HTG pattern at baseline had a 9.5 RR (95% CI: 3.4, 26.7) for the development of NOD compared to NL. HTG who developed NOD were younger, had higher GGT, and higher GGT to platelet ratio (GPR) compared to HTG who did not develop NOD. From the results, the study developed a nomogram to predict risk of outcome using US findings, GPR, and age.