Novel potential approach to prevent infection in patients with liver failure

January 9, 2014

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 occurs when there is rapid death of (hepatocytes). According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) drug-induced liver injury, particularly acetaminophen (Tylenol®) overdose, is the most common cause of 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 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."

Explore further: Survival 'excellent' following living donor liver transplantation for acute liver failure

More information: "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).

Related Stories

Research tackles liver transplant failure

November 7, 2013

The re-infection of transplanted livers with hepatitis C virus (HCV) – which can irreparably damage the new organ - could be halted by administering a drug which blocks the virus entering the liver, research from the University ...

Recommended for you

Bile acid uptake inhibitor prevents NASH / fatty liver in mice

September 21, 2016

Drugs that interfere with bile acid recycling can prevent several aspects of NASH (nonalcoholic steatohepatitis) in mice fed a high-fat diet, scientists from Emory University School of Medicine and Children's Healthcare of ...

New therapeutic target for Crohn's disease

September 20, 2016

Research from the Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies a promising new target for future drugs to treat inflammatory bowel disease (IBD). The study, published today in Cell Reports, also indicates ...

Mosquitoes, Zika and biotech regulation

September 19, 2016

In a new Policy Forum article in Science, NC State professor Jennifer Kuzma argues that federal authorities are missing an opportunity to revise outdated regulatory processes not fit for modern innovations in biotechnology, ...

Arthritis drug may help with type of hair loss

September 22, 2016

(HealthDay)—For people who suffer from a condition that causes disfiguring hair loss, a drug used for rheumatoid arthritis might regrow their hair, a new, small study suggests.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.