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News

New algorithm predicts acute liver failure in drug-induced liver injury

This month's issue of Gastroenterology examines the use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury.

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Hy's Law, which states that hepatocellular drug-induced liver injury with jaundice indicates a serious reaction, is used widely to determine risk for acute liver failure.

Dr Isabel Lucena and colleagues from Spain optimized the definition of Hy's Law, and developed a model for predicting acute liver failure in patients with drug-induced liver injury.

The researchers collected data from 771 patients with drug-induced liver injury from the Spanish DILI registry, from 1994 through 2012.

The team analyzed data collected at drug-induced liver injury recognition, and at the time of peak levels of alanine aminotransferase (ALT) and total bilirubin.

Of the 771 patients with drug-induced liver injury, 32 developed acute liver failure.

Hepatocellular injury, female sex, high levels of total bilirubin, and a high ratio of aspartate aminotransferase (AST):ALT were independent risk factors for acute liver failure.

An R-based model identified patients who developed acute liver failure with 67% specificity
Gastroenterology

The research team compared 3 ways to use Hy's Law to predict which patients would develop acute liver failure.

All included total bilirubin greater than 2-fold the upper limit of normal (×ULN), and either ALT level greater than 3 × ULN, a ratio (R) value of 5 or greater, or a new ratio (nR) value of 5 or greater.

At recognition of drug-induced liver injury, the R- and nR-based models identified patients who developed acute liver failure with 67% and 63% specificity, respectively, whereas use of only ALT level identified them with 44% specificity.

However, the level of ALT and the nR model each identified patients who developed acute liver failure with 90% sensitivity, whereas the R criteria identified them with 83% sensitivity.

The team found an equal number of patients who did and did not develop ALF had alkaline phosphatase levels greater than 2 × ULN.

The researchers observed that an algorithm based on AST level greater than 17.3 × ULN, total bilirubin greater than 6.6 × ULN, and AST:ALT greater than 1.5 identified patients who developed acute liver failure with 82% specificity and 80% sensitivity.

Dr Lucena's team concludes, "When applied at drug-induced liver injury recognition, the nR criteria for Hy's Law provides the best balance of sensitivity and specificity whereas our new composite algorithm provides additional specificity in predicting the ultimate development of acute liver failure."

Gastroenterol 2014: 147(1): 109–118.e5
03 July 2014

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