studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1045A
and relates to NAFLD disease severity. We speculate that tissue
hypoxia allows for functional activation of Hypoxia Inducible
Factor 1α with subsequent induction of genes important in
epithelial-mesenchymal transition, including SHh, and NAFLD
progression.
Disclosures:
Ronald J. Sokol - Advisory Committees or Review Panels: Yasoo Health, Inc.; Consulting:
Roche, Ikaria, Otsuka American Pharmaceuticals, Alnylam, Retrophin;
Grant/Research Support: Mead Johnson Nutritionals, Lumena, FFF Enterprises
The following authors have nothing to disclose: Shikha Sundaram, Marzena
Swiderska-Syn, Zhaoxing Pan, Ann C. Halbower, Kelley E. Capocelli, Kristen N.
Robbins, Anna Mae Diehl
1716
Risk Factors Associated with Cystic Fibrosis-associated
Liver Disease (CFLD)
Tamir A. Miloh 1,2 , Amanda Pope 1 , John Daye 3 , Chengcheng Hu 3 ,
Peggy Radford 1 ; 1 Phoenix Children, Phoenix, AZ; 2 Mayo Clinic,
Scottsdale, AZ; 3 University of Arizona, Tucson, AZ
Cystic fibrosis-associated liver disease (CFLD) affects approximately
30% of patients and is a significant cause of morbidity
and mortality. Aims: Analyze data from the CF registry to
determine the predictors significant towards the development
and progression of CFLD. We analyzed 39642 unique and
valid observations documented on routine annual visits from
1986 to present. Categorical, quantitative and ordinal variables
were analyzed using Pearson’s Chi-squared test, 2-group
t-test with Welsh degree of freedom modification and the
independent 2-group Mann-Whitney U-test, respectively. The
following phenotypes were further analyzed (n and %): any
liver disease (11,002, 28%), gallstones (480, 1.7%), cirrhosis
(1735, 4.5%), steatosis (150, 0.5%), non-cirrhotic liver disease
(3513, 9%) and other (5124, 13.2%). Complications of cirrhosis
(n and % of patients with cirrhosis) include gastric or esophageal
varices (191, 22.9%), gastrointestinal bleeding (292,
22.3%), splenomegaly and hypersplenism (302, 36%) and
ascites (82, 9.8%). Variables were statistically significant at
the p-valueG (54) and 3876delA (8.4).
The following reduced risk of CFLD: Caucasian (0.65) and
diagnosis on newborn screening (NS) (0.4). (b) Gallstones: FTT
(1.43), steatorrhea (1.73), respiratory infection with pseudomonas
(2.79), burkholderia cepacia (1.7), fungal (1.84). Protective:
male gender (0.6) and NS (0.17). (c) Cirrhosis: male
gender (1.4), FTT (1.43), meconium ileus (1.75), steatorrhea
(1.33), respiratory infection with staphylococcal (1.4), pseudomonas
(3.35), burkholderia cepacia (1.65), fungal (1.7) and
F508 mutations (1.44). Mean chloride sweat concentration
was 5.62 mmol/L higher than those without cirrhosis. Protective:
NS (0.28) and mutations: R117H (0.23), 2789+5G>A
(0.05) and 3849+10kbC>T (0.16). (d) Steatosis: mutations
Q890X (26.66) and 218delA (8.86). The mean age of death
for patients with cirrhosis was 2.24 years less than those without
cirrhosis. Conclusion: Analyzing the largest CF database
revealed that CFLD leads to earlier mortality and male gender,
non-Caucasian, meconium ileus, malnutrition, increased sweat
chloride, certain respiratory infections and mutation were associated
with increased risk of CFLD and other mutations were
protective.
Disclosures:
The following authors have nothing to disclose: Tamir A. Miloh, Amanda Pope,
John Daye, Chengcheng Hu, Peggy Radford
1717
Hepatic Manifestations in Adenosine Deaminase-Deficient
Severe Combined Immune Deficiency
Shilpa Lingala 1 , Elizabeth Garabedian 2 , Fabio Candotti 2 , David
E. Kleiner 4 , Kenneth J. Wilkins 3 , Theo Heller 1 , Christopher Koh 1 ;
1 Liver Diseases Branch, National Institute of Diabetes and Digestive
and Kidney Diseases, NIH, Bethesda, MD; 2 National Human
Genome Research Institute, NIH, Bethesda, MD; 3 Office of the
Director, National Institute of Diabetes, Digestive and Kidney Diseases,
Bethesda, MD; 4 Laboratory of Pathology, National Cancer
Institute, Bethesda, MD
Background: Adenosine deaminase-deficient severe combined
immune deficiency (ADA-SCID) is a rare autosomal recessive
metabolic disorder that occurs in