The current method for assessing medication-related liver injury is not providing an accurate picture of some medications’ toxicity—or lack thereof—to the liver, according to a new study led by researchers from the Perelman School of Medicine. Classification of a medication’s potential to damage the liver, termed “hepatotoxicity,” has been historically determined by counting individual reported cases of acute liver injury (ALI). Instead, the researchers used real-world health care data to measure rates of ALI within a population and uncovered that some medications’ levels of danger to the liver are being misclassified, in a paper published in JAMA Internal Medicine.
“Incidence rates of severe ALI can be a valuable tool for determining a medication’s toxicity to the liver and when patients should be monitored, since incidence rates provide a truer, real-world look at this toxicity. Case reports did not accurately reflect observed rates of ALI because they do not consider the number of persons exposed to a medication, and cases of drug-induced liver injury are often underreported,” says senior author Vincent Lo Re.
Within the study, 17 different medications had rates that exceeded five severe ALI events per 10,000 “person-years,” a measure that reflects both the amount of people in a group and how long the study observes them. The team determined that 11 of these medications were in lower categories of hepatoxicity by case counts that were likely not reflective of their true risk, since their incidence rates revealed higher levels of toxicity.
To determine incidence rates, Lo Re and his team, including lead author Jessie Torgersen, an assistant professor of medicine, examined electronic medical record data on almost 8 million people. Each person did not have pre-existing liver or biliary disease when they began taking any of the 194 medications that were studied. Each of those medications were analyzed due to suspicion that they could cause harm to the liver, since each had more than four published reports of liver toxicity associated with their use.
On the other side of the hepatotoxicity coin, the researchers found eight medications that were classified as the most hepatotoxic based on the number of published case reports, but should actually be in the least liver-toxic group, with incidence rates of less than one severe ALI event per 10,000 person-years.
With these findings, the researchers hope that there might soon be mechanisms established within electronic medical records to alert clinicians to closely monitor the liver-related laboratory tests of patients who start a medication with a high observed rate of severe ALI.
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