A study by researchers at King's College London indicates 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).
The 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 overdose, is the most
common cause of acute liver failure in the United States 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 per cent of 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 Harry Antoniades, an MRC Clinician Scientist
from King's College London and Imperial College London. "Our study
is the first to investigate the role of a 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 urgently needed."
The paper, Secretory leukocyte protease inhibitor: A pivotal mediator of
anti-inflammatory responses in acetaminophen induced acute liver
failure, is published in Hepatology.