Features of Severe Liver Disease With Portal Hypertension in Patients With Cystic Fibrosis

Abstract

Background & Aims Liver disease is the third leading cause of death in patients with cystic fibrosis (CF), but features of patients with CF, severe liver disease, and portal hypertension have not been fully characterized. Methods We performed a retrospective analysis of data from 561 patients with CF (63% male, 99% with pancreatic insufficiency), liver disease (hepatic parenchymal abnormalities consistent with cirrhosis, confirmed by imaging), and portal hypertension (esophageal varices, portosystemic collaterals, or splenomegaly), with no alternate causes of liver disease. All patients were enrolled in the Genetic Modifier Study of Severe CF Liver Disease at 76 international centers, from January 1999 through July 2013. Results Male patients were diagnosed with liver disease at a younger age than female patients (10 vs 11 years; P=.01). Splenomegaly was observed in 99% of patients and varices in 71%. Levels of liver enzymes were near normal in most patients. Thrombocytopenia affected 70% of patients and was more severe in patients with varices (88×109/L vs 145×109/L; P<.0001). Ninety-one patients received liver transplants (16%), at a median age of 13.9 years. Compared to patients who did not receive liver transplants, patients who received liver transplants had lower platelet counts (78×109/L vs 113×100/L; P<.0001), higher international normalized ratios (P<.0001), and lower levels of albumin (P=.0002). The aminotransferase to platelet ratio index (APRi) and fibrosis index based on 4 factor (FIB-4) values were above diagnostic thresholds for CF liver disease in 96% and 90% of patients, respectively. Patients who received liver transplants or who had varices had higher APRi and FIB-4 values than patients who did not. Conclusions In patients with CF, severe liver disease develops early in childhood (around 10 years of age) and is more common in boys than girls. Patients with varices and those who receive liver transplants have more abnormal platelet counts and APRi and FIB-4 scores.

Cystic Fibrosis Liver Disease: Outcomes and Risk Factors in a Large Cohort of French Patients

“…The prevalence of severe CFLD was higher in male patients, in patients homozygous for the CFTR F508del mutation, and in patients with a history of meconium ileus at birth. An international study based on 561 CF patients with severe CFLD (cirrhosis and portal hypertension) showed similar results . The complications were mostly cirrhosis and portal hypertension, as shown by others .…”

Adult‐onset cystic fibrosis liver disease: Diagnosis and characterization of an underappreciated entity

“…This is timely given that the FibroScan is approved by the US Food and Drug Administration for clinical use, which has resulted in increased availability in many advanced medical centers that routinely provide care to CF patients. Similarly, studies evaluating noninvasive fibrosis markers (specifically APRI and FIB‐4) have solely been performed in children with CFLD . In this study, with the long duration of follow‐up, we were able to expand on the experience of these biomarkers in pediatrics in addition to demonstrating their utility in identifying adults who develop CFLD.…”

A Multidisciplinary Approach to Pretransplant and Posttransplant Management of Cystic Fibrosis–Associated Liver Disease

“…In‐depth evaluation of biomarker indices, such as aspartate aminotransferase‐to‐platelet ratio index (APRI) and Fibrosis‐4, and advanced imaging modalities, such as transient elastography (TE) and acoustic radiation force impulse, have been shown to accurately reflect advanced liver disease/end‐stage fibrosis in CF. However, they have not yet been shown to predict outcomes, thus limiting their application in the selection of patients for LT …”