Liver disease in cystic fibrosis: A prospective study on incidence, risk factors, and outcome

CF Center, Department of Pediatrics, University of Milan, Italy.
Hepatology (Impact Factor: 11.19). 01/2003; 36(6):1374-82. DOI: 10.1053/jhep.2002.37136
Source: PubMed

ABSTRACT Incidence of liver disease (LD) associated with cystic fibrosis (CF) and its clinical characterization still is unsettled. We have assessed prospectively the incidence and risk factors of this complication, and its impact on the clinical course of CF. Between 1980 and 1990, we enrolled 177 CF patients without LD in a systematic clinical, laboratory, ultrasonography screening program of at least a 10-year duration. During a 14-year median follow-up (2,432 patient-years), 48 patients developed LD, with cirrhosis already present in 5. Incidence rate (number of cases per 100 patient-years) was 1.8% (95% confidence interval: 1.3-2.4), with sharp decline after the age of 10 years and higher risk in patients with a history of meconium ileus (incidence rate ratio, 5.5; 2.7-11), male sex (2.5; 1.3-4.9), or severe mutations (2.4; 1.2-4.8) at multivariate analysis. Incidence of cirrhosis was 4.5% (2.3-7.8) during a median period of 5 years from diagnosis of liver disease. Among the 17 cirrhotic patients, 13 developed portal hypertension, 4 developed esophageal varices, 1 developed liver decompensation requiring liver transplantation. Development of LD did not condition different mortality (death rate ratio, 0.4; 0.1-1.5) or higher incidence of other clinically relevant outcomes. In conclusion, LD is a relatively frequent and early complication of CF, whose detection should be focused at the first life decade in patients with history of meconium ileus, male sex, or severe genotype. Although LD does not condition a different clinical course of CF, in some patients it may progress rapidly and require liver transplantation.

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    • "e l s e v i e r . c o m / l o c a t e / y a b i o [21] [29] [23] [30] [31]. Depending on the country, the IRT cutoff value currently used for CF newborn screening ranges between 65 and 70 ng ml –1 [32] [33] [34]. "
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    ABSTRACT: The purpose of this study was to develop a silica nanoparticle-based immunosensor with laser-induced fluorescence (LIF) as a detection system. The proposed device was applied to quantify the immunoreactive trypsin (IRT) in cystic fibrosis (CF) newborn screening. A new ultrasonic procedure was used to extract the IRT from blood spot samples collected on filter papers. After extraction, the IRT reacted immunologically with anti-IRT monoclonal antibodies immobilized on a microfluidic glass chip modified with 3-aminopropyl functionalized silica nanoparticles (APSN–APTES-modified glass chips). The bounded IRT was quantified by horseradish peroxidase (HRP)-conjugated anti-IRT antibody (anti-IRT–Ab) using 10-acetyl-3,7-dihydroxyphenoxazine (ADHP) as enzymatic mediator. The HRP catalyzed the oxidation of nonfluorescent ADHP to highly fluorescent resorufin, which was measured by LIF detector, using excitation lambda at 561 nm and emission at 585 nm. The detection limits (LODs) calculated for LIF detection and for a commercial enzyme-linked immunosorbent assay (ELISA) test kit were 0.87 and 4.2 ng ml−1, respectively. The within- and between-assay variation coefficients for the LIF detection procedure were below 6.5%. The blood spot samples collected on filter papers were analyzed with the proposed method, and the results were compared with those of the reference ELISA method, demonstrating a potential usefulness for the clinical assessment of IRT during the early neonatal period.
    Analytical Biochemistry 10/2014; 463:31–37. DOI:10.1016/j.ab.2014.06.016 · 2.22 Impact Factor
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    • "On the contrary, fibrosis staging on liver biopsy, whose accuracy was improved by dual-passes, predicted the development of PHT [3]. Even so, liver biopsy has several drawbacks including sampling error as the histologic lesions of CFLD are unevenly distributed throughout the liver parenchyma [1], inaccuracy of liver biopsy due to intra and inter variability of histopathological interpretation [6], high cost, possible risk, and health-care resource utilization. Thus, invasive liver biopsy is poorly suited as diagnostic test for such a prevalent condition and there is need for a continuous search for minimally invasive, sensitive and quick means of detection of clinically important liver disease. "
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    ABSTRACT: Acoustic radiation force impulse (ARFI) is a novel technique for the measurement of hepatic stiffness, which could be valuable in clinical follow-up of patients affected by cystic fibrosis liver disease (CFLD). Seventy-five patients with suspected CFLD (35 males) underwent clinical and ultrasonographic evaluations, liver and pulmonary function tests, ARFI investigation, and upper gastrointestinal endoscopy. Ten ARFI measurements were taken at the deep right hepatic lobe to compute median values of Shear Wave Velocity (SWV) for each individual. SWV increased progressively from 1.02m/s (95%, Confidence Interval, CI, 0.92-1.126) in patients with no evidence of CFLD at ultrasonography (N=16), to 1.12 (95%CI 1.049-1.19) in patients with CFLD and no signs of portal hypertension (PHT, N=23), and to 1.25 (95%CI 1.14-1.358) in those with CFLD and signs of PHT (N=28). SWV was 1.63 (95%CI 1.26-1.99) in patients with oesophageal varices (N=8) (p<0.0001). ARFI may represent an easy, fast and non-invasive tool for the clinical follow-up of patients with cystic fibrosis associated liver disease.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 04/2012; 11(5):427-32. DOI:10.1016/j.jcf.2012.04.001 · 3.82 Impact Factor
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    • "The majority of patients with CF-related liver disease present in their first decade. The incidence and progression of liver disease in the paediatric population are well described [21] [22] [23] and liver transplantation is an established therapy for end-stage liver disease in children with CF [24]. Few studies have addressed the prevalence and natural history of liver disease in adults with CF, so the impact of liver disease on patients surviving into adulthood is uncertain. "
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    ABSTRACT: Liver disease is an important cause of death in adults with cystic fibrosis (CF). Ursodeoxycholic acid (UDCA) may slow progression. Managing varices and timely evaluation for liver transplantation are important. Adults with CF underwent annual review. Abnormalities of liver function tests or ultrasound prompted referral to the CF/liver clinic where UDCA was commenced. Endoscopic surveillance for varices was undertaken if ultrasound suggested portal hypertension. 154 patients were followed for a median 5 years. 43 had significant liver disease, 29 had cirrhosis with portal hypertension and 14 had ultrasound evidence of cirrhosis without portal hypertension. All started UDCA. Only one patient developed chronic liver failure and none required liver transplantation. 27 underwent endoscopy; 1 required variceal banding, the others had insignificant varices. Ultrasound was normal in 97 patients while five had steatosis; nine further patients had splenomegaly but no other evidence of portal hypertension. Neither spleen size nor platelet count correlated with portal hypertension. Liver disease was common in adults with CF but disease progression was rare. Thus liver disease detected and closely monitored in adults appeared to have a milder course than childhood CF. Splenomegaly, unrelated to portal hypertension may be a consequence of CF.
    Journal of Cystic Fibrosis 06/2008; 7(3):252-7. DOI:10.1016/j.jcf.2007.10.004 · 3.82 Impact Factor
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