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Idiosyncratic drug-induced liver injury is a diagnosis of exclusion, expert says

PHILADELPHIA — Due to its nature, idiosyncratic drug-induced liver injury is a diagnosis of exclusion, making it elusive and clinically challenging.

“You have patients with drug-induced liver injury in your practice,” Naga P. Chalasani, MD, a professor of cellular and integrative physiology at the Indiana University School of Medicine in Bloomington, Ind., said in the David Y. Graham Lecture during the ACG Annual Scientific Meeting. “Idiosyncratic drug-induced liver injury remains a clinical and basic science challenge.”

Naga P. Chalasani

Chalasani noted that idiosyncratic drug-induced liver injury (DILI) is generally rare, but that clinicians need to understand where it may exist and how it may behave.

The most common culprits are antimicrobials and dietary herbal supplements, according to Chalasani.

“But I stress that any compound can cause idiosyncratic DILI,” he said.

For example, TNF-a antagonists have demonstrated a hepatocellular pattern of injury, while tyrosine kinase inhibitors (TKIs) have been associated with alanine aminotransferase elevation. Cardiovascular and central nervous system agents could also cause DILI, as might antineoplastics.

Outcomes associated with each class of drugs can be difficult to predict, but Chalasani stressed that there is minimal evidence that DILI is dose-related. He added that idiosyncrasy can be immunologic or metabolic. “But even in cases where it seems metabolic, there may be evidence of immune underpinnings,” he said.

Chalasani described idiosyncratic DILI as a diagnosis of exclusion. “You need to look closely at your patient’s history,” he said. “If there are negative tests for hepatitis and an absence of alcoholism, shock or autoimmunity, DILI may be present.”

Clinicians should also conduct imaging studies of the liver and biliary tree. “If you have a patient with suspected idiosyncratic DILI, it is important to identify whether it is cholestatic or hepatocellular,” he said. “A lot of times you can just look at the liver enzyme pattern and tell.”

The phenotypes can be broad and the etiology is generally unknown, he added.

For more information:

Chalasani N. David Y. Graham Lecture. Presented at: Annual ACG Scientific Meeting, Oct. 20-22, 2014; Philadelphia, PA.

Disclosures: Chalasani reports associations with Abbott, Aegirion, Cumberland, Galectin, Gilead, Intercept, Lilly and Salix.