Hepatic steatosis in Wilson disease – Role of copper and PNPLA3 mutations

摘要: Background & Aims The earliest characteristic alterations of the liver pathology in Wilson disease (WD) include steatosis, which is sometimes indistinguishable from non-alcoholic fatty (NAFLD). Steatosis WD may reflect copper-induced mitochondrial dysfunction. A genetic polymorphism rs738409, patatin-like phospholipase domain-containing 3 gene ( PNPLA3 ), strongly associated with appearance NAFLD. This study evaluated role and hepatic copper content for development steatosis patients WD. Methods Liver biopsies obtained at diagnosis genotype were analyzed 98 Caucasian (male: 52 [53.1%]; mean age: 27.6years [CI 95%: 24.8–30.4, range: 5.8–61.5]). was graded as percentage lipid containing hepatocytes by an expert hepatopathologist unaware results testing. Results Moderate/severe (>33% hepatocytes) observed 28 (pediatric: n=13/26 [50.0%], adult: n=15/72 [20.8%]; p =0.01). Forty-six (46.9%; pediatric: n=7, n=39; =0.022) had cirrhosis. Multivariate logistic regression identified G allele (OR: 2.469, CI 1.203–5.068; =0.014) pediatric age 4.348; 1.577–11.905; =0.004) independent variables moderate/severe steatosis. In contrast, did not impact on 1.000, 1.000–1.001; =0.297). Conclusions common contributes to its pathogenesis. concentration ATP7B mutations deserve further investigations.