for Managing Acetaminophen-related Liver Disease and Acute Liver Failure|
number of patients with acute liver failure (ALF) is growing in one way that can
be prevented: toxicity due to acetaminophen (marketed as Tylenol and many other
brands and generics). Therapeutic advances are improving the outlook for people
with acetaminophen hepatotoxicity, though some of these are not yet ready for
an American Association for the Study of Liver Disease (AASLD) clinical symposium
held at the annual Digestive Disease Week meeting (DDW
2009) taking place this week in Chicago, 4 experts in the field offered a
look at future strategies for preventing and treating acetaminophen-related liver
disease, according to DDW Daily News, the official conference newspaper.
is not only something that we need to be aware of, but so do others all around
us," said Robert Fontana, MD, director of the Liver Transplant Program at
the University of Michigan Health System at Ann Arbor. Between 1998 and 2004,
he noted, the proportion of ALF cases caused by acetaminophen toxicity increased
from 28% to 51%.
past year the ALF Study Group looked at the link between the acetaminophen and
liver disease, and found that accidental and intentional ingestion of high doses
of the drug -- sometimes as a suicide attempt -- was the most common cause for
ALF; for women, acetaminophen-related liver failure constituted a large majority
of the cases. The second most common cause of ALF among both men and women was
idiosyncratic pharmacological reactions (unpredictable and unusual individuals
factor that contributes to accidental overdose is that acetaminophen is an ingredient
in many compound medications, including those sold over the counters. People may
combine such products and end up taking more than the total recommended dose.
Dr. Fontana said that heightened vigilance for acetaminophen misuse is warranted,
but so is early recognition of overdose as cause of ALF.
order to diagnose acetaminophen hepatotoxicity quickly, Dr. Fontana recommended
that it should be assumed until proven otherwise if a patient's records indicate
a history of previous toxic ingestion. Another good screen is ALT greater than
1000 IU/mi with normal bilirubin. In addition, symptoms of ALF are well established
and dramatic, including altered mental status -- including coma -- and extreme
vasodilatation as well as kidney and lung failure.
overdose is associated with the highest rate of transplant-free survival -- about
two-thirds -- in short-term studies. It is treatable with gastric lavage ("stomach
pumping"), charcoal, and N-acetylcysteine (NAC).
studies of NAC suggested that it might also be effective for people with ALF due
to causes other than acetaminophen poisoning. A multicenter trial in which patients
were randomized by coma grade and other factors showed no improvement in overall
3-week survival in those treated with intravenous NAC compared with placebo; however,
the researchers did observed a trend toward differences in length of hospital
stay, and the study is continuing.
another presentation, Rajiv Jalan, MBBS, from the London Clinic in the U.K. noted
that NAC also helps control inflammation in the brain, one of the most lethal
manifestations of ALF. Although ammonia remains central to the pathogenesis of
encephalopathy in people with ALF, management of elevated ammonia constitutes
"an unmet clinical need," he said.
a bioartificial liver in conjunction with an extracorporeal liver-assist device
is one method that warrants more study, said Norman Sussman, MD, of the University
of Utah at Salt Lake City. Non-metabolic liver support methods developed thus
far are simple, but relatively ineffective, and in many cases a new liver is needed.
prophylactic hypothermia (chilling) to treat ALF due to acetaminophen toxicity
has also known promise, according to Todd Stravitz, MD, of Virginia Commonwealth
University in Richmond. Hypothermia also shows benefits when used therapeutically
for uncontrolled intracranial hypertension.
experts take therapeutic, preventive aim at acetaminophen overdose. DDW Daily
News. Digestive Disease Week (DDW 2009). Chicago. June 2, 2009.