An ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis

doi:10.1016/0168-8278(95)80444-7

Journal of Hepatology

Volume 22, Issue 5, May 1995, Pages 513-521

https://doi.org/10.1016/0168-8278(95)80444-7 Get rights and content

Abstract

Advances in the management of the pulmonary complications of cystic fibrosis may result in an increasing prevalence of patients with chronic liver disease which may, therefore, become more important in the long-term management of cystic fibrosis patients. However, no simple and reliable test is available for the diagnosis of liver disease in cystic fibrosis. In particular percutaneous liver biopsy is highly inacurrate and potentially dangerous.

Imaging techniques, including real-time ultrasound scanning, have been used to evaluate the hepato-biliary system in cystic fibrosis and may represent the best available techniques for documenting hepatic involvement.

The purposes of this study were to construct an ultrasound scoring system using three cardinal features of hepatic ultrasound in cystic fibrosis: coarseness of the parenchyma, nodularity of the liver edge and increased periportal echogenecity, to enable the accurate, early diagnosis of liver involvement in cystic fibrosis. The scoring system was validated by correlating the results against ultrasound markers of portal hypertension, clinical and haemotological data.

The scoring system proved to be reproducible and to correlate well with the markers of hepatic disease detailed above. The results also suggest that the scoring system may allow the identification of patients with pre-cirrhotic chronic liver disease and so may prove of value in selecting a sub-group of patients more likely to respond to therapy.

References (39)

RA Nagel et al.
Liver disease and bile duct abnormalities in adults with cystic fibrosis
Lancet
(1989)
N Graham et al.
Cystic fibrosis: ultrasonographic findings in the pancreas and hepatobiliary system correlated with clinical data and pathology
Clin Radiol
(1985)
M Oellerich et al.
Lignocaine metabolite formation as a measure of pre-transplant liver function
Lancet
(1989)
AEA Joseph et al.
Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease
Clin Radiol
(1991)
JA Zagzebski et al.
Quantitative ultrasound imaging: in vivo results in normal liver
Ultrason Imaging
(1993)
D Lebrec et al.
Portal hypertension, size of esophageal varices, and risk of gastrointestinal bleeding in alcoholic cirrhosis
Gastroenterology
(1980)
Y-S Huang et al.
Measuring lidocaine metabolite - monoethylglycinexylidide as a quantitative index of hepatic function in adults with chronic hepatitis and cirrhosis
J Hepatol
(1993)
GF Vawter et al.
Cystic fibrosis in adults: an autopsy study
Pathol Annu
(1979)
I MacLusky et al.
Cystic fibrosis
Cystic fibrosis in the United Kingdom 1977-1985, an improving picture
Br Med J
(1988)

MS. Tanner

Liver and biliary problems in cystic fibrosis

J R Soc Med

(1992)

MM Van Ness et al.

Is liver biopsy useful in the evaluation of patients with chronically elevated liver enzymes?

Ann Intern Med

(1989)

S Sherlock et al.

G Garcia-Tsao et al.

Outpatient liver biopsy: how safe is it?

Ann Intern Med

(1993)

M. Bodian

Fibrocystic Disease of the Pancreas

(1952)

PA di Sant'Agnese et al.

A distinctive type of biliary cirrhosis of the liver associated with cystic fibrosis of the pancreas

Pediatrics

(1956)

KJ Gaskin et al.

Liver disease and common-bile-duct stenosis in cystic fibrosis

N Engl J Med

(1988)

RC Wilson-Sharp et al.

Ultrasonography of the pancreas, liver, and biliary system in cystic fibrosis

Arch Dis Child

(1984)

JM McHugo et al.

Ultrasound findings in children with cystic fibrosis

Br J Radiol

(1987)

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Reliable markers are needed for early diagnosis and follow-up of liver disease in Cystic Fibrosis (CF).
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This study demonstrated excellent diagnostic performance of TE, SWE and MRE for the diagnosis of CFLD.
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Cystic fibrosis liver disease (CFLD) affects a large proportion of cystic fibrosis (CF) patients; however encephalopathy is a rare complication. While classical hepatic encephalopathy can be a feature of end-stage liver disease, “hyperammonemic encephalopathy” can be precipitated in previously stable CFLD by various triggers including systemic corticosteroids. We describe one such case and review the relevant literature.
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To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease.
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All patients included into the study were clinically stable, homozygous for the ΔF508 mutation, over 5 years of age, already undergoing azithromycin treatment for at least 3 months, able to perform lung function tests and swallow capsules, and invited to participate between October 2008 and April 2010. The exclusion criteria were: (1) upper or lower respiratory infection within 2 weeks before baseline evaluation or abnormalities on chest X-ray or CT scan; (2) undergoing any chronic (>1 week daily) oral or intravenous anti-inflammatory treatment other than azithromycin within 3 months before study initiation; (3) active bleeding or increased risk of bleeding; (4) coagulation alterations and/or platelets < 50.000/mm3; (5) diabetes; (6) FEV1<40%; (7) significant liver disease, defined as elevated liver function values 2-fold higher than the upper normal range or abnormal ultrasound (Williams score >5 [28]); (8) hypercholesterolemia (>240 mg%); (9) participating in another study; (10) pregnancy. Sixteen patients agreed to participate but one patient was excluded on account of incident diabetes revealed at the baseline visit.
Effectiveness of omega-3 supplementation in cystic fibrosis (CF) remains controversial. This study sought to evaluate clinical status, exercise tolerance, inflammatory parameters, and erythrocyte fatty acid profile after 1 year of oral omega-3 supplementation in CF patients. Fifteen ΔF508-homozygous patients undergoing chronic azithromycin were randomized to receive omega-3 fish oil supplementation at a dose of 60 mg/Kg/day or placebo. In comparison with the previous year, in the supplemented group, the number of pulmonary exacerbations decreased at 12 months (1.7 vs. 3.0, p<0.01), as did the duration of antibiotic therapy (26.5 days vs. 60.0 days, p<0.025). Supplementation significantly increased the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as early as <3 months of administration, with concomitant decreases in arachidonic acid (AA) levels. This pilot study suggests that long-term omega-3 supplementation offers several clinical benefits as to the number of exacerbations and duration of antibiotic therapy in CF patients.
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An ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis

Abstract

Lancet

Clin Radiol

Lancet

Clin Radiol

Ultrason Imaging

Gastroenterology

J Hepatol

Cystic fibrosis in adults: an autopsy study

Pathol Annu

Cystic fibrosis

Cystic fibrosis in the United Kingdom 1977-1985, an improving picture

Br Med J

Liver and biliary problems in cystic fibrosis

J R Soc Med

Is liver biopsy useful in the evaluation of patients with chronically elevated liver enzymes?

Ann Intern Med

Outpatient liver biopsy: how safe is it?

Ann Intern Med

Fibrocystic Disease of the Pancreas

A distinctive type of biliary cirrhosis of the liver associated with cystic fibrosis of the pancreas

Pediatrics

Liver disease and common-bile-duct stenosis in cystic fibrosis

N Engl J Med

Ultrasonography of the pancreas, liver, and biliary system in cystic fibrosis

Arch Dis Child

Ultrasound findings in children with cystic fibrosis

Br J Radiol