Treatment for early stage acute liver failure

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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 scientists 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.

As per a research findings reported in the recent issue of Gastroenterology, scientists observed 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 main author of the study. "NAC is an excellent therapy 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 therapy if the failure was from non-acetaminophen causes.

To test NAC's use in non-acetaminophen cases, scientists 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 therapy.

Scientists observed that 52 percent of acute liver failure patients in mild to moderate comas survived when treated with NAC, in comparison to just 30 percent of those treated with only a placebo. In patients experiencing more severe coma, therapy 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 therapy 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 treatment for acute liver failure not caused by acetaminophen poisoning to determine optimal dosing and duration.


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