More from Aspen Webinar 2021. This blog entry has abbreviated/summarized several presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well. Great lecture from Jim Squires.
Cystic Fibrosis Liver Disease (CFLD) is variably defined
Risk factors include male patients, DeltaF508 mutations, meconium ileus and SERPINA1 Z allele
Two main phenotypes: Classic “Focal Biliary Cirrhosis” and Obliterative Portal Venopathy (increasingly recognized)
Intestinal microbiome and gut permeability/endotoxins may influence liver disease
Treatments: ursodeoxycholic acid may be helpful but overall evidence is low quality. Cochrane review does NOT recommend its routine use
A recent retrospective study (P-Y Boelle et al. Hepatology 2019; 69: 1648-56, associated editorial 1379-81) examines a large cohort of 3,328 patients with cystic fibrosis and pancreatic insufficiency (born after 1985) who were followed into a longitudinal “French CF Modifier Gene Study.”
Background from editorial:
Cystic fibrosis liver disease (CFLD) has been thought to occur mainly before puberty with ~40% of patients developing biochemical or ultrasonographic signs of liver involvement by age 12 years.
Registry studies have shown slow progression of liver disease with the development of cirrhosis and portal hypertension in 5-10% of patients. Due to difficulty identifying those at high risk for disease progression and the long time course, it has been impractical to complete definitive clinical trials to establish whether any therapies alter the natural history.
Ursodeoxycholic acid (UDCA) is the only current treatment available for CFLD; UDCA has been shown to have beneficial effects on biochemistries and liver stiffness, but effects on survival or need for transplantation are unknown.
Concerns have been raised about the potential for toxic UDCA metabolites (eg. lithocholic acid) in part based on unfavorable results of high-dose UDCA with primary sclerosing cholangitis
Key findings of this current study:
The incidence of CFLD increased “by approximately 1% every year, reaching 32.2% by age 25”
The incidence of severe CFLD increased “only after age 5, reaching 10% by age 30.”
Risk factors for CFLD and severe CFLD: male sex, CFTR F508del homozygosity, and history of meconium ileus.
Earlier introduction of UDCA (over the last 20 years) “did not change the incidence of severe CFLD.”
My take: This study confirms a previous study showing that CFLD occurs also in adulthood (Koh C et al. Hepatology 2017; 66:591-601) and adds further doubt about whether UDCA is beneficial.
Related article: AJ Freeman et al. “A Multidisciplinary Approach to Pretransplant and Posttransplant Management of Cystic Fibrosis-Associated Liver Disease” Liver Transplantation 2019; 25: 640-57.