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Medication
effective for Acute Liver Failure in early
stages of disease
Newswise — The antidote for acute liver failure caused by
acetaminophen poisoning also can treat acute
liver failure due to most other causes if
given before severe injury occurs, UT
Southwestern Medical Center researchers and
their colleagues at 21 other institutions
have found.
Acute liver failure occurs when cells in the liver die
quickly, resulting in toxins being released
into the bloodstream and brain. Patients
often end up in a hepatic coma as a result
of toxins not being cleared by the failing
liver.
Known causes of acute liver failure include autoimmune
hepatitis, drug-induced liver injury,
hepatitis A and B, and acetaminophen
poisoning.
In a study published in the September issue of
Gastroenterology, researchers
found that acute liver failure patients in
early stages of hepatic comas, when treated
with the medicine N-acetylcysteine (NAC),
were nearly 2.5 times more likely to survive
than those treated only with a placebo.
“NAC is safe, easy to administer, doesn’t require intensive
care and can be given in community
hospitals,” said Dr. William M. Lee,
professor of internal medicine at UT
Southwestern and lead author of the study.
“NAC is an excellent treatment for non-acetaminophen acute
liver failure if the disease is caught
early.”
Acute liver failure affects about 2,000 people annually in
the U.S., and 50 percent of those cases are
caused by acetaminophen poisoning. Until
this study, liver transplantation was the
only treatment if the failure was from
non-acetaminophen causes.
To test NAC’s use in non-acetaminophen cases, researchers
at 22 sites randomly assigned
non-acetaminophen acute liver failure
patients by the level of their coma, with
those with mild to moderate coma in one
group, and patients with more severe coma in
the other group.
Beginning in 1999 and continuing for eight years, 173
patients received either NAC or a placebo
for 72 hours. Doctors recorded patient
survival three weeks after they were placed
on treatment.
Researchers found that 52 percent of acute liver failure
patients in mild to moderate comas survived
when treated with NAC, compared to just 30
percent of those treated with only a
placebo.
In patients experiencing more severe coma, treatment with
NAC did not result in a significant
difference in survival rates.
“That makes sense because patients with advanced comas
typically die or get a transplant within a
few days,” said Dr. Lee, principal
investigator of the Acute Liver Failure
Study Group, a national consortium of liver
centers formed in 1997 to increase research
into the rare disease.
“This study establishes NAC as a treatment for
non-acetaminophen acute liver failure
patients in mild to moderate coma and
provides the first glimmer of hope that
something can help these direly ill
patients,” Dr. Lee said.
He said he will continue to study NAC as a therapy for
acute liver failure not caused by
acetaminophen poisoning to determine optimal
dosing and duration.
Other UT Southwestern researchers involved in the study
included Dr. Linda Hynan, professor of
clinical sciences and psychiatry; Dr. Anne
Larson, associate professor of internal
medicine; and Dr. Joan Reisch, professor of
clinical sciences and family and community
medicine.
Other Acute Liver Failure Group investigators involved in
the study were from the University of
California, Davis; the University of
Michigan; Virginia Commonwealth University;
University of California, San Francisco;
Baylor University Medical Center; University
of Nebraska; and the National Institute of
Diabetes and Digestive and Kidney Diseases.
The study was funded in part by the National Institutes of
Health, the Food and Drug Administration,
and the Northwestern Medical Foundation.
The N-acetylcysteine used was supplied by Apothecon/Geneva
Pharmaceuticals, a division of Bristol Myers
Squibb and Cumberland Pharmaceuticals.
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