Low hepatic copper content and PNPLA3 polymorphism in non-alcoholic fatty liver disease in patients without metabolic syndrome

Albert Friedrich Stättermayer, Stefan Traussnigg, Elmar Aigner (Co-Autor/-in), Christian Kienbacher, Ursula Huber-Schönauer (Co-Autor/-in), Petra Steindl-Munda, Andreas Stadlmayr, Friedrich Wrba, Michael Trauner, Christian Datz, Peter Ferenci

Publikation: Beitrag in FachzeitschriftOriginalarbeitBegutachtung

31 Quellenangaben (Web of Science)

Abstract

INTRODUCTION: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is multifactorial including metabolic, genetic (e.g. PNPLA3 [patatin-like phospholipase domain-containing 3 gene]), viral factors and drugs. Besides, there is evidence for a role of copper deficiency. Aim of the study was to evaluate the role of hepatic copper content, PNPLA3 in NAFLD patients with and without metabolic syndrome (MetS).

METHODS: One-hundred seventy-four NAFLD patients, who underwent liver biopsy for diagnostic work-up, were studied. Diagnosis of MetS was based on the WHO Clinical Criteria. Steatosis was semiquantified as percentage of fat containing hepatocytes and was graded according to Brunt. Histological features of non-alcoholic steatohepatitis (NASH) were assessed using the Bedossa classification. Hepatic copper content (in μg/g dry weight) was measured by flame atomic absorption spectroscopy. SNP rs738409 in PNPLA3 was investigated by RT-PCR.

RESULTS: Mean hepatic copper content was 22.3 (19.6-25.1) μg/g. The mean percentage of histologically lipid containing hepatocytes was 42.2% (38.3-46.0) and correlated inversely with hepatic copper content (ρ=-0.358, P<0.001). By subgroup analysis this inverse correlation remained significant only in patients without MetS (OR: 0.959 [CI95%: 0.926-0.944], P=0.020). Presence of minor allele (G) of PNPLA3 was also associated with moderate/severe steatosis (≥33%) both in patients with (OR: 2.405 [CI95%: 1.220-4.744], P=0.011) and without MetS (OR: 2.481 [CI95%: 1.172-5.250], P=0.018), but was only associated with NASH (OR: 2.002 [CI95%: 1.062-3.772], P=0.032) and liver fibrosis (OR: 2.646 [CI95%: 1.299-5.389], P=0.007) in patients without MetS.

CONCLUSION: Hepatic copper content and PNPLA3 mutations are associated with disease activity in NAFLD patients without MetS. Presence of MetS appears to mask the effects of hepatic copper and PNPLA3.

OriginalspracheEnglisch
Seiten (von - bis)100-107
Seitenumfang8
FachzeitschriftJOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
Jahrgang39
DOIs
PublikationsstatusVeröffentlicht - Jan. 2017

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