Unexplained acute liver failure is often acetaminophen toxicity.

SAN DIEGO -- As many as 18%-20% of cases of indeterminate acute liver failure may be the result of unrecognized acetaminophen toxicity, according to a presentation at the annual Digestive Disease Week.

The etiology is unknown in about 15% of cases of acute liver failure (ALF), said Dr. Niraj Khandelwal of the University of Texas, Dallas. Using a novel assay that detects acetaminophen (APAP) protein adducts, the Acute Liver Failure Study Group had determined in a previous study that adducts were present in 7 (19%) of 36 cases diagnosed as indeterminate ALF. The APAP adduct levels were comparable with those seen in patients with known acetaminophen overdose (Gastroenterology 2006;130:687).

To further evaluate indeterminate ALF, the authors conducted a larger study using a newer assay--high-performance liquid chromatography with electrochemical detection (HPLC-EC)--that is more efficient and more sensitive, Dr. Khandelwal said.

The assays were conducted on sera from 113 patients in the ALF Study Group registry. The serum samples were taken on the first or second day after admission and were collected from 1998 to 2006.

Of the 113, there were 32 with known APAP overdose, 93 who were adduct negative, and 20 (18%) who were adduct positive (defined using a cut point of 1 nmol/mL). Of those 20 patients, 9 (45%) died or received transplants and 11 (55%) spontaneously survived. Eight patients were given N-acetylcysteine (NAC), and six (75%) of those eight patients survived. Only 5 patients (42%) of the 11 who spontaneously survived did so without NAC.

The clinical and lab findings of the patients who had adducts equal to 1 nmol/mL or greater were consistent with findings--including very high aminotransferases, low bilirubin, and favorable outcome--for known APAP overdose patients. The median bilirubin level was 5.05 mg/dL, compared with 24.5 mg/dL for patients with negative adducts (1 nmol/mL or less).

The study confirms previous data showing that as many as one in five patients with indeterminate ALF actually has unrecognized acetaminophen toxicity, Dr. Khandelwal said. Given these data and the lack of an adduct assay that can be used at the bedside in real time, NAC should be considered in patients with indeterminate ALF who match the biochemical profile for APAP overdose, he said.

Dr. Khandelwal had no disclosures.

BY ALICIA AULT

Associate Editor, Practice Trends