Stonebraker J, Ooi C, Pace R, Corvol H, Knowles M, Durie P, Ling S

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 (88x10(9)/L vs 145x10(9)/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 (78x10(9)/L vs 113x10(0)/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 (FIB4) 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 FIB4 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 high platelet counts and APRI and FIB4 scores.

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