Background & Aims Cystic fibrosis liver disease (CFLD), a leading cause of death in cystic fibrosis (CF), is mostly described in pediatric populations. Adult-onset CFLD lacks sufficient characterization and diagnostic tools. Methods A cohort of CF patients without CFLD during childhood were followed for up to 38 years with serologic testing, imaging, and noninvasive fibrosis markers. Historical CFLD diagnostic criteria were compared with a newly proposed CFLD criteria. Results 36 CF patients were followed for a median of 24.5 years(IQR=15.6, 32.9). By the last follow-up, 11(31%) had died. With conventional criteria, 8(22%) patients had CFLD, and by new criterion, 17 (47%) had CFLD at a median age of 36.6 years(IQR=26.5, 43.2). By new criterion, those with CFLD had higher median ALT(42 vs 27, p=0.005), AST(26 vs 21, p=0.01), direct bilirubin(0.13 vs 0.1, p=0.01), PT(14.4 vs 12.4, p=0.002), and APRI(0.31 vs 0.23, p=0.003) over the last two years of follow-up. Subjects with a Fibroscan® >6.8kPa had higher ALT(42 vs 28U/L, p=0.02), AST(35 vs 25U/L, p=0.02), APRI(0.77 vs 0.25, p=0.0004), FIB-4(2.14 vs 0.74, p=0.0003) and lower platelet counts(205 vs 293, p=0.02). One CFLD patient had nodular regenerative hyperplasia. Longitudinally, mean platelet counts significantly declined in the CFLD group(310 to 230U/L, p=0.0005). Deceased CFLD patients had lower platelet counts than those alive with CFLD(143 vs 258 U/L, p=0.004) or those deceased with no CFLD(143 vs 327U/L, p=0.006). Conclusion Adult-onset CFLD may be more prevalent than previously described which suggests a later wave of CFLD that impacts morbidity. Routine liver tests, radiologic imaging, noninvasive fibrosis markers and fibroscan® can be utilized algorithmically to identify adult CFLD. Further evaluation in other CF cohorts should be performed for validation.

Background The American Association for the Study of Liver Diseases (AASLD) practice guidelines provide recommendations in diagnosing and managing patients with liver disease from available scientific evidence in combination with expert consensus opinions. Aim To systematically review the evolution of recommendations from AASLD guidelines and identify gaps limiting the evidence-based foundations of these guidelines. Methods Initial and current AASLD guidelines published from January 1998 to August 2012 were reviewed. The AGREE II instrument was used to evaluate rigour and transparency of guideline development. The number of recommendations, distribution of grades (strength or certainty), classes (benefit versus risk) and types of recommendations were evaluated. Whenever possible, multiple versions were evaluated for evolving scientific evidence. Results A total of 991 recommendations from 28 guidelines on 17 topics were evaluated. From initial to current guidelines, the total number of recommendations increased by 36%(512 to 699). The largest increases were from chronic hepatitis B (HBV) (+71), liver transplantation (+53) and autoimmune hepatitis (AIH) (+27). Most current recommendations are grade II (44%) and less than 20% are grade I. The AGREE II evaluation showed global improvement in guideline quality. Both HBV and chronic hepatitis C guidelines had greatest increases in grade I recommendations (+383% and +67%, respectively). The greatest increases in treatment recommendations were from HBV (grade I, +1150%), liver transplantation (grade II, +112%) and AIH (grade III, +105%). Conclusions Despite significant increases in the numbers of recommendations within AASLD practice guidelines over time, only a minority are supported by grade I evidence, highlighting the need for developing well-designed investigations to provide evidence for areas of uncertainty and improving the quality of future guidelines in hepatobiliary diseases.