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Drug-induced liver injury is the most common reason for a drug to be withdrawn from the market. A new study seeks to determine risk factors for medications and identify individuals who may be at risk for liver damage from certain drugs.

Even if a drug is safe for most patients, it may not be safe for everyone. The most common reason a medication does not receive approval from the Food and Drug Administration, or has to be pulled from the market after FDA approval, is its effect on the liver.

Dr. Keyur Patel, an assistant professor in the Division of Gastroenterology at Duke University Medical Center, is one of the researchers working on a multi-center, large-scale study of drug-induced liver injury (DILI). He said the DILI Network is an effort to help identify clinical, environmental and genetic susceptibility factors that may lead certain drugs to increase the risk of acute liver injury.

"We've known about the effects of drugs on the liver for over 50 years," said Patel. "But with recently well-publicized drugs that have been withdrawn from the market due to drug-induced liver injury, there's been an increased focus on coming up with better definitions of what constitutes drug-induced liver injury.

"The DILI Network, which is sponsored by the U.S. National Institutes of Health (NIH) and the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), involves five centers throughout the country, covering several million people. The study data from these centers is being coordinated at the Duke Clinical Research Institute.

The idea is to initially come up with better definitions of drug-induced liver injury and thereafter collect information and biological samples from patients with well-defined cases of drug-induced liver injury. These will hopefully lead us in the future to genetic-type predictors of which patients may be susceptible to a particular drug."

Patel says the study will help identify genetic and environmental factors that may put some patients at risk for drug-induced liver injury, either from a single drug or from the interaction of prescription drugs, over-the-counter or herbal medicines, even certain recreational drugs.

"Every drug goes through the liver. The liver metabolizes any drug that goes through it, detoxifies it and aids in its removal from the body. Clearly, the more combinations of medications one takes, the greater the potential for interaction between medications and the ability of the liver to handle these drugs."

Patel believes the study findings might eventually serve as a model for a broad-based patient profile, which would identify genetic and environmental risk factors for drug-induced liver injury.

"We hope so. Certainly in the future, coming up with a pharmacogenomic profile of a particular patient or their reaction to a particular drug would be the ideal. At the moment, our definitions are based on clinical and laboratory parameters, where we need a clearly defined temporal relationship to the ingestion of a drug, or exposure to a drug. We need certain laboratory and clinical, and maybe histological, parameters to say, well, this is a drug injury. Then, really, the only way to see if this really was a drug injury is to withdraw the drug and see if these changes regress. The only way beyond this to see if this really was a drug injury is through re-administration, which isn't advisable in many cases.

"We need better definitions and better predictive indices on trying to work out which patients may react to a particular drug. We hope in the future we have better ideas, and certainly genetic profiling in this regard would be important to develop."