BOSTON — Intravenous N-acetylcysteine increases transplant-free survival in patients with early-stage acute liver failure, Dr. William Lee said at the annual meeting of the American Association for the Study of Liver Diseases.
However, the drug appears to hold little benefit for patients in the later stages of the disease. “These patients typically survive only a very short period of time, and it's probably not of value to them,” said Dr. Lee of the University of Texas Southwestern Medical Center at Dallas.
He presented the results of a randomized, controlled trial in which 173 patients with acute, non-acetaminophen-related liver failure received either N-acetylcysteine (NAC) or placebo. The patients' mean age was 41 years. Their liver failure had a variety of etiologies, including viral hepatitis B (21%), drug-induced liver injury (26%), and autoimmune hepatitis (15%).
Patients were stratified into early- and late-stage liver failure by their hepatic encephalopathy scores. Early-stage patients (115) had a score of I (forgetfulness, agitation) or II (disorientation, asterixis). Late-stage patients (58) had a score of III (somnolence) or IV (coma).
Patients in the active group received an initial loading dose of NAC 150 mg/kg, followed by continuous infusions at lower doses for the next 72 hours.
Overall survival at 3 weeks was not significantly different between the active and placebo groups (70% vs. 67%). Nor was there a significant difference in transplant-free survival (27% vs. 45%). However, when Dr. Lee examined survival by encephalopathy grade, significant differences did emerge. Mean transplant-free survival in those with encephalopathy grades I and II was 52% in the active group, compared with 30% in the placebo group. NAC was associated with an 11-fold increase in the chance of transplant-free survival.
Overall, there were no significant differences in transplantation between the active and placebo groups (32% vs. 45%), length of hospital stay, or organ failure.
Although the drug appears both safe and effective at improving transplant-free survival for early-stage patients, “it is not a substitute for early referral for liver transplant,” Dr. Lee emphasized.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Food and Drug Administration's orphan products division.