Autoimmune-like drug-induced liver injury: a review and update for the clinician

ABSTRACT

Introduction: Autoimmune-like drug-induced liver injury (DI-AIH) is a rare but serious event with a growing body of scientific evidence and a fair degree of uncertainty.

Areas covered: This review covers the definition, pathophysiology, treatment and patient-centered outcomes of DI-AIH and presents up-to-date information on the most commonly implicated drugs.

Expert opinion: A high degree of clinical suspicion is required for the diagnosis of DI-AIH. This diagnosis should be considered in any patient with either acute or chronic elevations in liver-associated enzymes. Prevalence rates exceed 15% based on large international registry data. Autoantibodies, while common, are neither specific nor diagnostic of DI-AIH. Histology may be helpful in describing subtle differences between DI-AIH and de novo idiopathic autoimmune hepatitis (iAIH), but oftentimes the two are indistinguishable histologically. Alpha-methyldopa, fibrates, hydralazine, minocycline, nitrofurantoin, HMG-CoA reductase inhibitors (statins), iplimumab and tumor necrosis factor alpha antagonists are the most commonly associated drugs with DI-AIH. Complete recovery of liver injury is most often seen with DI-AIH, however, cases of prolonged injury may occur and may require treatment with immunosuppressive therapy. Relapse following cessation of corticosteroids for suspected DI-AIH should prompt reconsideration of the diagnosis and further exploration into possible iAIH.

KEYWORDS:

• Hepatology
• hepatotoxicity
• cirrhosis
• portal hypertension
• outcomes
• acute liver injury
• acute liver failure

Article highlights

• Autoimmune-like drug-induced liver injury (DI-AIH) is increasingly recognized and reported.

• Autoantibodies, while common, are neither specific nor diagnostic of DI-AIH.

• Advanced age and female gender appear to predispose one to DI-AIH.

• Liver biopsy may be helpful in describing subtle differences between DI-AIH and de novo idiopathic autoimmune hepatitis (iAIH), but oftentimes cannot distinguish between the two.

• Complete recovery following DI-AIH is expected, however, cases of prolonged injury may require treatment with immunosuppressive therapy.

• Relapse following cessation of corticosteroids for suspected DI-AIH should prompt reconsideration of the diagnosis and further exploration into possible iAIH.

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Declaration of interest

The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported in part by Health Resources and Services Administration contract 234-2005-370011C.