This is a prospective cohort follow-up study of 40 patients with

suspected CFLD: they were identified and referred by the CF clinic of JAK inhibitors in development the Royal Children’s Hospital (Brisbane, Australia), were enrolled between 1999 and 2004, and were followed until death, transplantation, or survival as of March 2009. This clinic is a major CF referral center (over 250 patients) for Queensland, Australia. The details and progress of all patients were recorded prospectively via a detailed clinical database. Suspected CFLD was defined as two of the following: (1) hepatomegaly (HM) with or without splenomegaly, (2) a persistent (>6-month) elevation of serum alanine aminotransferase (ALT; level > 1.5 × upper limit Z-VAD-FMK concentration of normal), and (3) abnormal liver US findings (abnormal echogenicity or a nodular edge). Those with liver synthetic dysfunction or a history of hepatobiliary surgery were excluded. The study conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the ethics committees of the Royal Children’s Hospital and the Queensland Institute of Medical Research. Informed consent was obtained from parents and, when appropriate, from patients. At enrollment, the following were performed

or determined for all patients: history, physical examination, Δf508 genotype, lung function, serum aminotransferases, liver synthetic function (international normalized ratio and albumin), and liver US as well as upper gastrointestinal endoscopy, serum draw for research, and dual-pass liver biopsy under general anesthesia. Specific note was made of the presence Montelukast Sodium or absence of PHT, which was defined as the occurrence of any of the following: endoscopic esophageal varices

and persistent clinical splenomegaly (palpable spleen below the left costal margin that was confirmed to span outside the normal range for the patient’s age by US) with or without thrombocytopenia (platelet count <150,000). Portal vein thrombosis was excluded by Doppler imaging. When PHT was present, the age of onset was recorded by chart review. During follow-up (up to 12 years), all patients received standard CF pulmonary and nutritional care, all patients with biopsy-confirmed fibrosis were prescribed ursodeoxycholic acid (15 mg/kg/day), and all patients were reviewed at least on a 6-month basis. For the purposes of this study, prospectively recorded follow-up data included clinical progress, occurrence of cystic fibrosis–related diabetes mellitus (CFRD; defined as insulin-dependent diabetes mellitus), survival, solid organ transplantation, forced expiratory volume in 1 second (FEV1), liver aminotransferases, liver synthetic function, and occurrence of PHT (as defined previously).