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Reuters Health Information (2014-01-13): Serine protease inhibitor may predict infection in acute liver failure


Serine protease inhibitor may predict infection in acute liver failure

Last Updated: 2014-01-13 15:02:44 -0500 (Reuters Health)

NEW YORK (Reuters Health) - A serine protease inhibitor may someday be key to treating infections stemming from acute liver failure, new research has found.

Levels of secretory leukocyte protease inhibitor (SLPI) rise during acetaminophen-induced acute liver failure, apparently modulating hepatic macrophages and monocytes as part of an anti-inflammatory response, according to the research.

When SLPI was included in cultured cells, it appeared to restrict infection-fighting monocytes and macrophages and allowed for the increase of lipopolysaccharides, which are associated with sepsis.

"Higher levels of SLPI are seen where there is more severe liver damage and a higher risk of infections and associated complications. We anticipate that this will give clinicians more accurate prediction of those patients who more likely to develop infection and enable prompt intervention with therapeutic strategies," lead investigator Dr. Harry Antoniades, a hepatologist at the Imperial College London and King's College London, told Reuters Health by email.

An SLPI blocker is under study now and a version of it may be commercially available within a few years, Dr. Antoniades says.

The researchers published their findings online November 27 in Hepatology.

The researchers evaluated data from 73 patients with acetaminophen-induced acute liver failure and 25 with acute liver failure that was not acetaminophen-induced, comparing them to two control groups, one comprised of 15 chronic liver disease patients and the other of 24 healthy volunteers.

They found higher levels of SLPI in the liver and in circulation in the drug-induced acute liver failure patients. They also found SLPI expression in biliary epithelial cells in cirrhotic livers, but not in normal livers. It also expressed in hepatic macrophages in necrotic tissue.

SLPI is a pivotal mediator of anti-inflammatory responses in AALF through modulation of monocyte/macrophage function which may account for the susceptibility to sepsis in AALF, earlier studies have shown.

"SLPI overproduction and its effects on immune responses are likely to be relevant in a number of conditions where there is a major insult to the body (e.g., septic shock major trauma, surgery, severe burns). We feel that the importance of this study lies in the fact that we highlight a mechanism of immunosuppression that leads to an increased susceptibility to infection and a poor outcome," Dr. Antoniades said.


Hepatology 2014.

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