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PUBLIC RELEASE DATE:
9-Jan-2014

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Contact: Dawn Peters
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Wiley

Novel potential approach to prevent infection in patients with liver failure

Findings published in the American Association for the Study of Liver Diseases journal, Hepatology, indicate that infection, the commonest cause of mortality in patients with acute liver failure (ALF), may be decreased by inhibiting the activity of a protein found in saliva called SLPI (secretory leukocyte protease inhibitor). New research has found that this protein, produced by the body in response to injury, plays a vital role in patients with ALF.

Acute liver failure occurs when there is rapid death of liver cells (hepatocytes). According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) drug-induced liver injury, particularly acetaminophen (TylenolŪ) overdose, is the most common cause of acute liver failure in the U.S. and other developed countries. Previous studies have demonstrated that infection is the commonest complication in liver failure and is the leading cause of premature death in over 50% patients.

"Infection, namely sepsis, in patients with acute liver failure may be linked to an inadequate response of the body's immune system," explains Dr. C.G. Antoniades, an MRC Clinician Scientist from Imperial College London and King's College London. "Our study is the first to investigate the role of this particular protein in liver failure patients."

A team of scientists and clinicians at King's College London, King's College Hospital NHS Foundation Trust and Imperial College London studied 98 patients with liver failure as well as 24 healthy volunteers. Results show that patients with ALF had elevated levels of this key molecule (SLPI) in the liver and circulating round the body, that impaired the ability of immune cells, monocytes/macrophages, to combat infection. When researchers blocked the activity of the SLPI molecule the function of monocytes/macrophages was restored, similar that seen in healthy individuals. When SLPI protein was added to healthy immune cells, it rendered them poorly responsive to infectious organisms that are commonly encountered in patients with liver failure.

"Our findings indicate that SLPI is a critical mediator of excessive anti-inflammatory responses in ALF which explains the susceptibility to sepsis/infection in these patients," concludes Dr. Antoniades. "Further study of therapeutic options to inhibit the activity of SLPI in the management of sepsis in liver failure are needed."

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This study is published in Hepatology. Media wishing to receive a PDF of the article may contact sciencenewsroom@wiley.com.

Full citation: "Secretory Leukocyte Protease Inhibitor: A Pivotal Mediator of Anti-Inflammatory Responses in Acetaminophen Induced Acute Liver Failure." Charalambos Gustav Antoniades, Wafa Khamri, Robin D Abeles, Leonie S Taams, Evangelos Triantafyllou, Lucia A Possamai, Christine Bernsmeier, Ragai R Mitry, Alistair O'Brien, Derek Gilroy, Robert Goldin, Michael Heneghan, Nigel Heaton, Wayel Jassem, William Bernal, Diego Vergani, Yun Ma, Alberto Quaglia, Julia Wendon and Mark Thursz. Hepatology; (DOI: 10.1002/hep.26933).

URL: http://doi.wiley.com/10.1002/hep.26933

Author Contact: Media wishing to speak with Dr. Antoniades may contact Sam Wong with Imperial College at sam.wong@imperial.ac.uk or Emma Reynolds with Kings College emma.reynolds@kcl.ac.uk.

About the Journal

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on is published by Wiley on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://wileyonlinelibrary.com/journal/hep.

About Wiley

Wiley is a global provider of content-enabled solutions that improve outcomes in research, education, and professional practice. Our core businesses produce scientific, technical, medical, and scholarly journals, reference works, books, database services, and advertising; professional books, subscription products, certification and training services and online applications; and education content and services including integrated online teaching and learning resources for undergraduate and graduate students and lifelong learners.

Founded in 1807, John Wiley & Sons, Inc. (NYSE: JWa, JWb), has been a valued source of information and understanding for more than 200 years, helping people around the world meet their needs and fulfill their aspirations. Wiley and its acquired companies have published the works of more than 450 Nobel laureates in all categories: Literature, Economics, Physiology or Medicine, Physics, Chemistry, and Peace. Wiley's global headquarters are located in Hoboken, New Jersey, with operations in the U.S., Europe, Asia, Canada, and Australia. The Company's website can be accessed at http://www.wiley.com.



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