Hepatic steatosis in Wilson disease--Role of copper and PNPLA3 mutations.
J Hepatol
; 63(1): 156-63, 2015 Jul.
Article
in En
| MEDLINE
| ID: mdl-25678388
ABSTRACT
BACKGROUND & AIMS:
The earliest characteristic alterations of the liver pathology in Wilson disease (WD) include steatosis, which is sometimes indistinguishable from non-alcoholic fatty liver disease (NAFLD). Steatosis in WD may reflect copper-induced mitochondrial dysfunction. A genetic polymorphism in rs738409, in the patatin-like phospholipase domain-containing 3 gene (PNPLA3), is strongly associated with appearance of in NAFLD. This study evaluated the role of PNPLA3 and hepatic copper content for development of steatosis in patients with WD.METHODS:
Liver biopsies obtained at diagnosis and the PNPLA3 genotype were analyzed in 98 Caucasian patients with WD (male 52 [53.1%]; mean age 27.6 years [CI 95% 24.8-30.4, range 5.8-61.5]). Steatosis was graded as percentage of lipid containing hepatocytes by an expert hepatopathologist unaware of the results of genetic testing.RESULTS:
Moderate/severe steatosis (>33% of hepatocytes) was observed in 28 patients (pediatric n=13/26 [50.0%], adult n=15/72 [20.8%]; p=0.01). Forty-six patients (46.9%; pediatric n=7, adult n=39; p=0.022) had cirrhosis. Multivariate logistic regression identified PNPLA3 G allele (OR 2.469, CI 95% 1.203-5.068; p=0.014) and pediatric age (OR 4.348; 1.577-11.905; p=0.004) as independent variables associated with moderate/severe steatosis. In contrast, hepatic copper content did not impact on moderate/severe steatosis (OR 1.000, CI 95% 1.000-1.001; p=0.297).CONCLUSIONS:
Steatosis is common in WD and the PNPLA3 G allele contributes to its pathogenesis. The role of hepatic copper concentration and ATP7B mutations in steatosis development deserve further investigations.Key words
Full text:
1
Database:
MEDLINE
Main subject:
DNA
/
Copper
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Hepatolenticular Degeneration
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Lipase
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Liver
/
Membrane Proteins
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Mutation
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Adult
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Child
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Child, preschool
/
Female
/
Humans
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Male
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Middle aged
Language:
En
Year:
2015
Type:
Article