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 (Tylenol®) 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.”
