Cystic Fibrosis–related Liver Disease

Debray, Dominique; Narkewicz, Michael R.; Bodewes, Frank; Colombo, Carla; Housset, Chantal; Jonge, Hugo R. de; Jonker, Johan W.; Kelly, Déirdre; Ling, Simon C.; Poynard, Thierry; Sogni, Philippe; Trauner, Michael; Witters, Peter; Baumann, Ulrich; Wilschanski, Michael; Verkade, Henkjan J.

doi:10.1097/mpg.0000000000001676

Cited by 94 publications

(90 citation statements)

References 51 publications

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“…Cases were thereafter split into ‘non-cirrhotic’ cases by combining categories 1 and 2 and ‘cirrhotic’ cases, combining categories 3 and 4. This is in broad concordance with recently agreed phenotypic categories of CFLD[16].…”

Section: Methodssupporting

confidence: 91%

The emerging burden of liver disease in cystic fibrosis patients: A UK nationwide study

et al. 2019

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Objective Cystic fibrosis associated liver disease (CFLD) is the third largest cause of mortality in CF. Our aim was to define the burden of CFLD in the UK using national registry data and identify risk factors for progressive disease. Methods A longitudinal population-based cohort study was conducted. Cases were defined as all patients with CFLD identified from the UK CF Registry, 2008–2013 (n = 3417). Denominator data were derived from the entire UK CF Registry. The burden of CFLD was characterised. Regression analysis was undertaken to identify risk factors for cirrhosis and progression. Results Prevalence of CFLD increased from 203.4 to 228.3 per 1000 patients during 2008–2013. Mortality in CF patients with CFLD was more than double those without; cirrhotic patients had higher all-cause mortality (HR 1.54, 95% CI 1.09 to 2.18, p = 0.015). Median recorded age of cirrhosis diagnosis was 19 (range 5–53) years. Male sex, Pseudomonas airway infection and CF related diabetes were independent risk factors for cirrhosis. Ursodeoxycholic acid use was associated with prolonged survival in patients without cirrhosis. Conclusions This study highlights an important changing disease burden of CFLD. The prevalence is slowly increasing and, importantly, the disease is not just being diagnosed in childhood. Although the role of ursodeoxycholic acid remains controversial, this study identified a positive association with survival.

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Section: Methodssupporting

confidence: 91%

The emerging burden of liver disease in cystic fibrosis patients: A UK nationwide study

et al. 2019

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“…In the liver, CFTR is expressed at the apical membrane of the cholangiocytes ( Cohn et al, 1993 ). Its absence or dysfunction leads to a decrease in bile flow, and the retention of endogenous hydrophobic bile acids that may be responsible for cell membrane injury ( Debray et al, 2017 ). This, in turn, causes inflammation and collagen deposition around the bile ducts and portal tracts, leading to focal biliary and periportal fibrosis, which can progress to multilobular cirrhosis with portal hypertension ( Feranchak and Sokol, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients

et al. 2018

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Cystic fibrosis (CF) is characterized by a chronic pulmonary inflammation. In CF, glucocorticoids (GC) are widely used, but their efficacy and benefit/risk ratio are still debated. In plasma, corticosteroid-binding globulin (CBG) binds 90% of GC and delivers them to the inflammatory site. The main goal of this work was to study CBG expression in CF patients in order to determine whether CBG could be used to optimize GC treatment. The expression of CBG was measured in liver samples from CF cirrhotic and non-CF cirrhotic patients by qPCR and Western blot and in lung samples from non-CF and CF patients by qPCR. CBG binding assays with 3H-cortisol and the measurement of the elastase/α1-antitrypsin complex were performed using the plasmas. CBG expression increased in the liver at the transcript and protein level but not in the plasma of CF patients. This is possibly due to an increase of plasmatic elastase. We demonstrated that pulmonary CBG was expressed in the bronchi and bronchioles and its expression decreased in the CF lungs, at both levels studied. Despite the opposite expression of hepatic and pulmonary CBG in CF patients, the concentration of CBG in the plasma was normal. Thus, CBG might be useful to deliver an optimized synthetic GC displaying high affinity for CBG to the main inflammatory site in the context of CF, e.g., the lung.

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“…Studies in animal models of biliary cirrhosis (rat) reported that PMF use vascular endothelial growth factor A-containing microparticles signaling for newly formed vessels, driving scar progression, while acting as mural cells[ 24 ]. This type of fibrosis progression originating from the portal tract is crucial in cystic fibrosis-related liver fibrosis[ 25 ]. In PBC epigenetic influence has been observed in the discordance of monozygotic twins.…”

Section: Cld: Common Pathogenic Mechanismsmentioning

confidence: 99%

Review: Pathogenesis of cholestatic liver diseases

Yokoda¹,

Rodríguez²

2020

WJH

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Cholestatic liver diseases (CLD) begin to develop after an impairment of bile flow start to affect the biliary tree. Cholangiocytes actively participate in the liver response to injury and repair and the intensity of this reaction is a determinant factor for the development of CLD. Progressive cholangiopathies may ultimately lead to end-stage liver disease requiring at the end orthotopic liver transplantation. This narrative review will discuss cholangiocyte biology and pathogenesis mechanisms involved in four intrahepatic CLD: Primary biliary cholangitis, primary sclerosing cholangitis, cystic fibrosis involving the liver, and polycystic liver disease.

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Cystic Fibrosis–related Liver Disease

Cited by 94 publications

References 51 publications

The emerging burden of liver disease in cystic fibrosis patients: A UK nationwide study

The emerging burden of liver disease in cystic fibrosis patients: A UK nationwide study

Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients

Review: Pathogenesis of cholestatic liver diseases

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