924 Non-Alcoholic Fatty Liver Disease Is Associated With Lower Levels of Physical Activity Measured via Accelerometry: The Framingham Heart Study

Abstract

Introduction: Cystic fibrosis liver disease (CFLD) is the 3rd leading cause of death in cystic fibrosis (CF) patients, contributing to 2.5-5% of overall mortality. Onset of CFLD has been mostly described in pediatric populations, but with improving life expectancy, adult onset CFLD is increasingly recognized with an estimated prevalence of 2-37%. Criteria for the diagnosis of adult CFLD are lacking and inconsistent; with few studies evaluating noninvasive biomarkers and radiographic data for classification systems. Aims: To characterize adult CFLD and develop a set of novel criteria for the diagnosis of adult CFLD utilizing biochemical, clinical and radiographic markers in an adult CF cohort followed at the NIH Clinical Center for up to 37 years (yrs). Methods: Patients with CF were evaluated with hepatic biomarkers of inflammation, synthetic function, portal hypertension, radiologic imaging, and transient elastography (TE). Charts were extracted for clinical data. Utilizing these biomarkers along with TE, APRI, and FIB-4, criteria were defined for the diagnosis CFLD. Patients who met CFLD criteria were compared to CF patients without evidence of liver disease. Results: 36 patients with CF (33% F508 homozygous, 23% F508 heterozygous) were studied (65% males, 97% white). The median age of CF diagnosis was 11 yrs, and the median follow-up duration was 23 yrs (range 2 to 37). At the time of last follow-up (mean age=46 yrs), 11 (31%) had died (respiratory failure=3, infection=3, complications of transplantation=2, or other causes=3). 17 of 36 (47%) patients met criteria for CFLD (mean age of diagnosis=31 yrs). Patients with CFLD had significantly higher mean ALT (44.3 vs 28.1, p=0.01), direct bilirubin (0.2 vs 0.1, p =0.04), PT (14.4 vs 12.8, p=0.01), and APRI (0.6 vs 0.2, p=0.04) over the last year of follow-up. In the CFLD group, 4 patients had radiographic evidence of advanced liver disease and 1 patient had nodular regenerative hyperplasia and experienced hepatic decompensation. On longitudinal comparison, platelet counts significantly declined in the CFLD group (312 to 237 U/L, p=0.007) as compared to patients without CFLD (328 to 297 U/L, p=0.11). Conclusions: By evaluating non-invasive markers of liver disease, a novel criteria can be employed to identify adult CFLD. These biomarkers not only suggest that a second wave of liver disease exists in adult CF patients, but also that it may be more prevalent than previously described. Further evaluation of this diagnostic criteria in other CF cohorts should be performed to evaluate its utility in adult CFLD.