Adult‐onset cystic fibrosis liver disease: Diagnosis and characterization of an underappreciated entity

Abstract

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.

Cystic Fibrosis Liver Disease: Outcomes and Risk Factors in a Large Cohort of French Patients

“…Furthermore, in these two studies, patients were only followed up over a short time, meaning that limited information was available to estimate CFLD incidence over the patients’ lifetime. In accordance with our findings, a recent study reported that adult‐onset CFLD was likely underestimated . The improved survival of patients with CF in the last decade may also explain the change in the incidence profiles of CFLD…”

The Efficacy of MRI in the diagnostic workup of cystic fibrosis-associated liver disease: A clinical observational cohort study

“…In general, CFLD is felt to be an emerging entity, Koh C. et al recently emphasized [39] the lack of sufficient characterisation and diagnostic tools for the diagnosis of adult-onset CFLD. They found that only 22% of CF patients had CFLD, based upon the Debray criteria, which they felt was likely an underestimation of actual disease.…”

Cystic Fibrosis–Associated Liver Disease in Lung Transplant Recipients

“…Factors independently associated with liver disease have included a history of meconium ileus, pancreatic insufficiency, colonization with Burkholderia cepacia , and the number of episodes per year requiring intravenous (IV) antibiotic therapy . Although early studies suggested that the majority of these cases are in pediatric patients, recent studies suggest that liver disease may be more common in adults with CF than previously predicted . This may be related to newer modalities for assessment of liver disease not previously available.…”

“…At the time of the initial consensus criteria proposed by Debray et al in 2011, there was insufficient validation to support the use of noninvasive methods of assessment of fibrosis, such as transient elastography, or to incorporate them into the definition of CFLD. More recent publications have proposed the inclusion of these fibrosis assessments and reliance on radiographic evidence of cirrhosis or diffuse liver disease, rather than on physical examination …”