Albert Friedrich Stättermayer1, Stefan Traussnigg1, Elmar Aigner2, Christian Kienbacher1, Ursula Huber-Schönauer3, Petra Steindl-Munda1, Andreas Stadlmayr3, Friedrich Wrba4, Michael Trauner1, Christian Datz3, Peter Ferenci5. 1. Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. 2. Department of Internal Medicine I, Paracelsus Private Medical University, Salzburg, Austria. 3. Department of Internal Medicine, KH Oberndorf, Oberndorf, Austria. 4. Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria. 5. Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. Electronic address: peter.ferenci@meduniwien.ac.at.
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. Copyright Â
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. Copyright Â
Authors: Anna Członkowska; Tomasz Litwin; Petr Dusek; Peter Ferenci; Svetlana Lutsenko; Valentina Medici; Janusz K Rybakowski; Karl Heinz Weiss; Michael L Schilsky Journal: Nat Rev Dis Primers Date: 2018-09-06 Impact factor: 52.329
Authors: Michael Mendoza; Shelley Caltharp; Ming Song; Lindsay Collin; Juna V Konomi; Craig J McClain; Miriam B Vos Journal: J Pediatr Gastroenterol Nutr Date: 2017-07 Impact factor: 2.839
Authors: M Mandorfer; B Scheiner; A F Stättermayer; P Schwabl; R Paternostro; D Bauer; B Schaefer; H Zoller; M Peck-Radosavljevic; M Trauner; T Reiberger; P Ferenci; A Ferlitsch Journal: Aliment Pharmacol Ther Date: 2018-06-29 Impact factor: 8.171
Authors: Georg Semmler; Benedikt Simbrunner; Bernhard Scheiner; Philipp Schwabl; Rafael Paternostro; Theresa Bucsics; Albert Friedrich Stättermayer; David Bauer; Matthias Pinter; Peter Ferenci; Michael Trauner; Mattias Mandorfer; Thomas Reiberger Journal: J Gastroenterol Hepatol Date: 2019-06-14 Impact factor: 4.029
Authors: Veera Raghavan Thangapandi; Oskar Knittelfelder; Mario Brosch; Eleonora Patsenker; Olga Vvedenskaya; Stephan Buch; Sebastian Hinz; Alexander Hendricks; Marina Nati; Alexander Herrmann; Devavrat Ravindra Rekhade; Thomas Berg; Madlen Matz-Soja; Klaus Huse; Edda Klipp; Josch K Pauling; Judith Ah Wodke; Jacobo Miranda Ackerman; Malte von Bonin; Elmar Aigner; Christian Datz; Witigo von Schönfels; Sophie Nehring; Sebastian Zeissig; Christoph Röcken; Andreas Dahl; Triantafyllos Chavakis; Felix Stickel; Andrej Shevchenko; Clemens Schafmayer; Jochen Hampe; Pallavi Subramanian Journal: Gut Date: 2020-06-26 Impact factor: 23.059
Authors: Timothy A Su; Diyala S Shihadih; Wendy Cao; Tyler C Detomasi; Marie C Heffern; Shang Jia; Andreas Stahl; Christopher J Chang Journal: J Am Chem Soc Date: 2018-10-15 Impact factor: 16.383