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Iron overload, chronic liver disease, and liver cancer

One in every 190 Australians of northern European descent suffers with the inherited iron-overload disorder Hereditary Haemochromatosis. Early detection prevents the development of iron-related organ injury effecting the liver, pancreas, musculoskeletal and endocrine systems. Chronic liver disease is a rapidly increasing cause of morbidity and death globally. A major contributor to the increasing burden of liver disease is hepatocellular carcinoma (HCC), which usually occurs as a complication of cirrhosis. The most common cause of cirrhosis, non-alcoholic fatty liver disease, is the liver complication of the disturbed metabolic state which is seen in obesity and diabetes mellitus. The research work undertaken by Professor Olynyk aims to improve the ability of:

  1. scientists to understand the injury mechanisms leading to these disorders,
  2. clinicians to detect, diagnose and treat individuals with these conditions to improve health outcomes, and;
  3. consumers to better understand their conditions.

Professor Olynyk partners with Universities (Edith Cowan University, Curtin University, The University of Western Australia, Murdoch University), the Australian Red Cross Blood Service, industry (Resonance Health), The WA Department of Health and consumers. In a world first, research knowledge related to Hereditary Haemochromatosis was formulated into an online referral system which has now become the national standard of care for referral and management of the disease in Australia. It has substantially improved access, timeframes and referral practices to the Australian Red Cross Blood Service, with significant productivity gains. Going forward, Professor Olynyk is now examining the role of disturbed iron metabolism in cancer, development of non-alcoholic fatty liver disease and the processes which occur in the liver as a result of injury which lead to cirrhosis and liver cancer.

For more information, contact Professor John Olynyk

Current projects

  • Iron metabolism in cancer
  • Non-alcoholic fatty liver disease
  • Pathogenesis of liver fibrosis and liver cancer

Research Team

Lead

Professor John Olynyk

Postdoctoral Researchers

  • Dr Nina Tirnitz-Parker
  • Dr Rodrigo Carlessi

HDR students

  • Mr Kedar Deshpande, PhD

Key publications

  1. Chin J, Powell LW, Ramm LE, Ayonrinde O, Ramm GA, Olynyk JK.  Utility of hepatic or total body iron burden in the assessment of advanced hepatic fibrosis in HFE hemochromatosis.  Scientific Reports. 2019;9:20234
  2. Mitchell T, McKinnon E, Ayonrinde O, Adams LA, Trinder D, Chua ACG, Newton RU, Straker L, Olynyk JK. Decreased physical working capacity in adolescents with non-alcoholic fatty liver disease associates with reduced iron availability. Clin Gastroenterol Hepatol 2020;18:1584-1591.
  3. Adris N, Hazeldine S, Bentley P, Trinder D, Chua ACG, Powell L, Ramm LE, Ramm G, Olynyk JK.  Detection of HFEHaemochromatosis in the clinic and community using standard erythrocyte tests.  Blood Cells Mol Dis. 2019;74:18-24.
  4. Adris N, Chua ACG, Knuiman MW, Divitini ML, Trinder D, Olynyk JK.  A prospective cohort examination of haematological parameters in relation to cancer death and incidence: The Busselton Health Study.  BMC Cancer 2018, 863. Open Access article
  5. Ayonrinde OT, Adams LA, Mori TA, Beilin LJ, de Klerk N, Pennell CE, Olynyk JK.  Sex differences between parental pregnancy characteristics and non-alcoholic fatty liver disease in adolescents.  Hepatology 2018; 67:108-122.
  6. Ong SY, Gurrin LC, Dolling L, Dixon J, Nicoll A, Wolthuizen M, Wood EM, Anderson GJ, Ramm GA, Allen KJ, Olynyk JK, Crawford D, Ramm LE, Gow P, Durant S, Powell LW, Delatycki MB.  Reduction of body iron in HFE-related haemochromatosis and moderate iron overload (Mi-Iron): a multicentre, participant-blinded, randomised controlled trial.   The Lancet Haematology 2017;4:e607-e614.
  7. Ayonrinde OT, Oddy WH, Adams LA, Mori TA, Beilin LJ, de Klerk N, Olynyk JK.  Infant nutrition and maternal obesity prospectively influence the risk of non-alcoholic fatty liver disease in adolescents.  J Hepatol 2017;67:568-576.
  8. Chua ACG, Knuiman MW, Trinder D, Divitini ML, Olynyk JK.  Higher concentrations of serum iron and transferrin saturation but not serum ferritin are associated with cancer outcomes.    AJCN 2016;104:736-742.
  9. Kohn-Gaone J, Dwyer BJ, Grzelak CA, Miller G, Shackel NA, Ramm GA, McCaughan GW, Elsegood CL, Olynyk JK, Tirnitz-Parker JEE.  Divergent inflammatory, fibrogenic and liver progenitor cell dynamics in two common mouse models of chronic liver injury.  Am J Pathol. 2016;186:1762-1774.
  10. Elsegood CL, Chan CW, Degli-Esposti MA, Wikstrom ME, Domenichini A, Lazarus K, van Rooijen N, Ganss R, Olynyk JK, Yeoh GCT.  Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration.  Hepatology 2015;62:1272-1284.
  11. Adams L Crawford D, Stuart K, House M, St Pierre T, Webb M, Ching H, Kava J, Bynevelt M, MacQuillan G, Garas G, Ayonrinde O, Mori T, Croft K, Niu X, Jeffrey G, Olynyk J.  The impact of phlebotomy in nonalcoholic fatty liver disease: A prospective randomized controlled trial.  Hepatology 2015;61:1555-1564.
  12. Prakoso E, Tirnitz-Parker J, Kayali Z, Lee A, Gan E, Ramm G, Kench J, Bowen D, Olynyk J, McCaughan G, Shackel N.  Analysis of the intrahepatic ductular reaction and progenitor cell responses in hepatitis C virus recurrence post-liver transplantation. Liver Transplantation 2014;20:1508-19.
  13. Knight B, Tirnitz-Parker J, Olynyk JK.  C-kit inhibition by imatinib mesylate attenuates progenitor cell expansion and inhibits liver tumour in formation in mice.  Gastroenterology 2008;135:969-979.
  14. Allen KJ, Gurrin LC, Constantine CC, Osborne NJ, Delatycki MB, Nicoll AJ, McLaren CE, Bahlo M, Nisselle AE, Vulpe CD, Anderson GJ, Giles GG, English DR, Hopper JL, Olynyk JK, Powell LW, Gertig DM. Iron-Overload-Related Disease in HFE  Hereditary Haemochromatosis. N Engl J Med. 2008;358:221-30.
  15. Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L and Powell LW. A population-based study of the clinical expression of the hemochromatosis gene.  N Engl J Med. 1999;341:718-724.
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