Interestingly, 8 of 23 Δf508 homozygotes, 7 of 11 Δf508 heterozygotes, and 2 of 6 ungenotyped children had or developed PHT during the course of the study. Three of eight children with CFRD at enrollment had PHT, and another two children developed PHT during follow-up. In this well-characterized, prospectively followed cohort of children with CF presenting with common clinical test findings indicating possible liver disease, we have demonstrated the importance of detecting liver fibrosis by liver biopsy to predict the occurrence of PHT, the poor performance of nonbiopsy

tests currently employed to detect or predict the development of clinically significant CFLD, and a high rate of future adverse outcomes. Although CFLD is CDK inhibitor the third leading cause of mortality in CF3 and accounts for less than 2% of directly caused deaths, the 17.5% mortality rate in this cohort, in which six of seven patients who died had PHT, might explain why significant liver diseases such as cirrhosis have a lower reported prevalence in adults versus children (2% versus 5%-10%).1-4 Such outcomes lend weight to the

importance of detecting selleck inhibitor and managing clinically significant CFLD in childhood. These data confirm and extend the results of previous studies,9 which found that clinical evaluation, serum aminotransferases, and US, despite continued widespread clinical Adenylyl cyclase practice,1, 5-7 are nonspecific for the detection of liver fibrosis and are imprecise for predicting the presence of or progression to PHT. Nevertheless, this study does gives support to the practice of performing these standard tests to screen for clinically significant liver disease in patients with CF because they identify a cohort of children with a 42% chance of developing significant liver

disease (i.e., PHT) versus the expected clinical prevalence of 4%,20 which is comparable to our clinical prevalence of 7% (17 of 240 patients; unpublished data, 2010). It is also noted that US abnormalities become more specific for higher stages of fibrosis and cirrhosis.8 Importantly, however, only fibrosis staging on liver biopsy predicted the development of clinically significant CFLD (defined by the occurrence of PHT) and the serious outcomes of transplantation or mortality; this indicates that biopsy has a relevant predictive role in the care and evaluation of patients with suspected CFLD. If liver biopsy is the gold standard for the diagnosis of hepatobiliary fibrosis in CF, sampling error concerns may be assuaged by dual-pass biopsy. Even though nine patients had clinical evidence of PHT at enrollment, only two had Scheuer stage 4 fibrosis, the histological criterion for established cirrhosis.