What are the mimics of Immune Checkpoint Inhibitor (ICI) induced hepatitis?

From the Guidelines

Immune checkpoint inhibitor (ICI) hepatitis mimics include autoimmune hepatitis, viral hepatitis, drug-induced liver injury, alcohol-related liver disease, and tumor progression to the liver, which must be ruled out through thorough serological testing, medication review, and imaging studies, as management differs significantly for each condition. When evaluating suspected ICI hepatitis, clinicians should first rule out viral causes through serological testing for hepatitis A, B, C, and E, as well as non-hepatotrophic viruses such as Epstein-Barr virus, cytomegalovirus, and herpes simplex virus 1. Drug-induced liver injury should be considered by reviewing all medications, including herbal supplements and over-the-counter drugs, and potentially hepatotoxic medications or dietary supplements should be avoided 1. Some key points to consider when evaluating ICI hepatitis include:

• Autoimmune hepatitis shares many features with ICI hepatitis, including elevated transaminases and positive autoantibodies, but typically has a more insidious onset
• Alcohol-related liver disease can be excluded through a thorough history
• Imaging studies like CT or MRI can help differentiate tumor progression from immune-mediated hepatitis
• Laboratory findings that suggest ICI hepatitis include acute elevation of ALT/AST (often >5x upper limit of normal), with or without elevated bilirubin, in the context of recent ICI therapy (typically within 6-12 weeks of initiation)
• Liver biopsy, while not always necessary, can be helpful in unclear cases, showing characteristic lymphocytic infiltration in ICI hepatitis 1. Distinguishing these mimics is crucial as management differs significantly—ICI hepatitis typically requires immunosuppression with corticosteroids (starting with prednisone 1-2 mg/kg/day), while viral hepatitis requires antiviral therapy and drug-induced injury necessitates medication discontinuation 1.

From the Research

Immune Checkpoint Inhibitor (ICI) Induced Hepatitis Mimics

The mimics of ICI induced hepatitis include:

• Drug-induced liver injury 2, 3, 4
• Autoimmune hepatitis 2, 3, 4, 5
• Other causes of acute hepatitis, such as viral hepatitis or alcoholic hepatitis, although these are not explicitly mentioned in the provided studies

Key Features of ICI Induced Hepatitis

Some key features that may help distinguish ICI induced hepatitis from its mimics include:

• Histological features, such as:
  • Predominantly lobular hepatitis with milder portal inflammation 4
  • Granuloma formations, which were seen in 90% of ICI-related liver injury cases 3
  • Lower CD4/8 ratio compared to autoimmune hepatitis and drug-induced liver injury 3
• Clinical features, such as:
  • Elevated liver enzymes, whereas hyper-bilirubinemia is less common 4
  • Absence of antinuclear antibodies or IgG elevations 4
• Response to treatment, such as:
  • Improvement with corticosteroid therapy, although patients with bile duct injury may have a poorer response 3

Diagnosis and Management

Liver biopsy may be helpful in diagnosing ICI induced hepatitis and distinguishing it from its mimics 2, 3, 4. Careful monitoring for immune-related adverse events, including hepatotoxicity, is essential when using ICIs 6, 5.