Lily Dara, MD, is a physician-scientist, hepatologist, and assistant professor of medicine at the University of Southern California.

Lily Dara, MD

Distinguishing Drug-Induced vs Classic Autoimmune Hepatitis, with Lily Dara, MD

Drug-induced autoimmune-like hepatitis (DI-ALH)

 is a rare subtype of idiosyncratic drug-induced liver injury (DILI) that closely mimics autoimmune hepatitis (AIH). While their presentation is similar, their management is not, underscoring the importance of differentiating between the two.

While distinguishing DI-ALH from classic AIH is critical for appropriate diagnosis and management, doing so is no easy feat – both conditions share nearly identical serological markers and histological features.

“It's really important to distinguish drug-induced autoimmune-like hepatitis from autoimmune hepatitis. Because if the patient is on nitrofurantoin and you stop it and the numbers come down, you really don't need immunosuppression,” Lily Dara, MD, a physician-scientist, hepatologist, and assistant professor of medicine at the University of Southern California, explained to 

She notes that in the case of persistent liver injury, immunosuppression is finite and patients can generally come off of prednisone within 4-6 months. If the patient does not relapse, Dara says this defines that it was drug-induced. If the patient relapses or continues to have injury, she says this indicates underlying idiopathic or classic AIH.

“Once you have autoimmune hepatitis in the differential, you still go down that pathway of diagnosis, which requires a liver biopsy,” Dara explained. “If you suspect it's a drug, you immediately stop the drug, and you watch the liver enzymes closely. If they don't come down, you start immunosuppression.”

She stresses the importance of long-term monitoring of these patients, noting that if it is a bout of AIH that was caught and treated quickly, patients can still relapse 1-2 years later. Accordingly, Dara says patients should be monitored for 5 years to ensure they do not manifest as having classic AIH.

She also highlights that some drugs known to trigger DI-ALH can be substituted for safer alternatives. Specifically, she cites the use of alpha-methyldopa for pregnancy-related hypertension and notes nifedipine or labetalol are guideline-recommended options that may be safer.

Dara goes on to discuss research into genetic predisposition, referencing studies from the Drug-Induced Liver Injury Network that explore HLA phenotypes and genetic markers associated with DI-ALH. However, due to small sample sizes, she says more extensive studies are needed to identify potential biomarkers and distinguish it from classic AIH.

Editors’ note: Dara has no relevant disclosures.

Tan CK, Ho D, Wang LM, Kumar R. Drug-induced autoimmune hepatitis: A minireview. World J Gastroenterol. doi:10.3748/wjg.v28.i24.2654

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Dara explains the importance of distinguishing DI-ALH from classic AIH, how their management differs, and where research in this field is heading.

Identifying Drug-Induced Autoimmune-Like Hepatitis, with Lily Dara, MD

 often demands lifelong immunosuppression, but what happens when a patient presents with AIH-like features—only for the culprit to be a medication?

Drug-induced autoimmune-like hepatitis (DI-ALH) is a rare subtype of idiosyncratic drug-induced liver injury (DILI) that closely mimics AIH. Distinguishing between the 2 is essential but complicated by the fact that both DI-ALH and idiopathic AIH share nearly identical serological markers and histological features.

“What's really interesting here is that drug-induced autoimmune-like hepatitis seems to be associated with some specific drugs that can trigger this autoimmune-like reaction,” Lily Dara, MD, a physician-scientist, hepatologist, and assistant professor of medicine at the University of Southern California, explained to 

. “Of course, it needs to be differentiated from autoimmune hepatitis because if you have a diagnosis of autoimmune hepatitis, that basically says you need lifelong immunosuppression… but this is self-limiting.”

Dara goes on to describe how liver biopsy can help differentiate between the two, calling attention to differences in the amount of fibrosis in patients with AIH versus those with DI-ALH. In DI-ALH, she says the short course of exposure to drugs that can cause it, most commonly nitrofurantoin, minocycline, alpha methyldopa, and hydralazine, does not allow enough time to develop significant fibrosis.

“While it's not a foolproof mechanism, the presence of fibrosis underlying chronicity points to classic or de novo autoimmune-like hepatitis,” she explained. “When you run across these cases, make sure you have a very good liver pathologist review it and maybe consult some experts in the disease.”

Dara also notes that anti-tumor necrosis factor (TNF) drugs like infliximab, adalimumab, and etanercept have been associated with DI-ALH, as have statins. Additionally, cases of DI-ALH have been observed with use of khat, or Bushman’s tea, a flowering plant native to eastern and southeastern Africa used as a stimulant.

Dara describes similarities between drug-induced autoimmune-like hepatitis and idiopathic autoimmune hepatitis, as well as how to differentiate them.

Lily Dara, MD

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