TY - JOUR
T1 - Low hepatic copper content and PNPLA3 polymorphism in non-alcoholic fatty liver disease in patients without metabolic syndrome
AU - Stättermayer, Albert Friedrich
AU - Traussnigg, Stefan
AU - Aigner, Elmar
AU - Kienbacher, Christian
AU - Huber-Schönauer, Ursula
AU - Steindl-Munda, Petra
AU - Stadlmayr, Andreas
AU - Wrba, Friedrich
AU - Trauner, Michael
AU - Datz, Christian
AU - Ferenci, Peter
N1 - Aigner: Department of Internal Medicine I, Paracelsus Private Medical University, Salzburg, Austria; Huber-Schönauer, Stadlmayr, Datz:Department of Internal Medicine, KH Oberndorf, Oberndorf, Austria
PY - 2017/1
Y1 - 2017/1
N2 - 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.
AB - 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.
KW - HEPATOCELLULAR-CARCINOMA
KW - CONFERS SUSCEPTIBILITY
KW - WIDE ASSOCIATION
KW - NATURAL-HISTORY
KW - SCORING SYSTEM
KW - OBESE-PATIENTS
KW - RISK-FACTORS
KW - STEATOHEPATITIS
KW - STEATOSIS
KW - POPULATION
U2 - 10.1016/j.jtemb.2016.08.006
DO - 10.1016/j.jtemb.2016.08.006
M3 - Original Article
C2 - 27908400
SN - 0946-672X
VL - 39
SP - 100
EP - 107
JO - JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
JF - JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
ER -