Randomized patients were stratified

Randomized patients were stratified by coma
grade, with the majority of patients
having low-grade encephalopathy (64%). The major causes of NAI-ALF
in the study participants were nonacetaminophen
drug-induced liver
toxicity (26%), hepatitis B virus infection
(21.4%), and autoimmune
hepatitis (15%). There was no difference
in the primary outcome of
overall survival rate at three weeks
with i.v. acetylcysteine compared
with placebo (70% versus 66%, p =
0.28). However, the transplant-free
survival rate significantly increased
with the use of acetylcysteine compared
with placebo (40% versus 27%,
p = 0.04). This increase in transplantfree
survival was particularly striking
in patients with low-grade encephalopathy
(52% versus 30%, p = 0.01),
while the transplant-free survival
rate did not significantly differ in
patients with high-grade encephalopathy
receiving i.v. acetylcysteine
versus placebo, respectively (9% versus
22%, p = 0.912). There were also
nonsignificant differences in transplantation
rates (32% for acetylcysteine
versus 45% for placebo, p = 0.093)
and length of hospital stay (9 days
for acetylcysteine versus 13 days for
placebo, p = 0.056). When outcomes
were considered within each etiologic
cause of NAI-ALF, acetylcysteinetreated
patients with drug-induced
liver toxicity or hepatitis B virus
infection had higher rates of overall
and transplant-free survival than
acetylcysteine-treated patients with
other causes of NAI-ALF. Unfortunately,
inferential statistical analyses
were not performed for these comparisons
due to the low number of
patients in each etiologic group. Low
enrollment occurred overall as well,
taking nearly eight years to enroll an
adequate number of patients in each
group.