Investigational New Drugs

, Volume 31, Issue 4, pp 1071–1077 | Cite as

Ipilimumab associated hepatitis: imaging and clinicopathologic findings

  • Kyung Won KimEmail author
  • Nikhil H. Ramaiya
  • Katherine M. Krajewski
  • Jyothi P. Jagannathan
  • Sree Harsha Tirumani
  • Amitabh Srivastava
  • Nageatte Ibrahim


Ipilimumab is a novel immunomodulator demonstrating promising efficacy in treatment of melanoma and other cancers. The clinical benefit from ipilimumab can be hampered by the immure-related adverse events (irAEs) caused by dysregulation of host immune system. Ipilimumab associated hepatitis is also an important irAE, however, there have been limited descriptions of its clinicopathologic and imaging characteristics. We aim to describe the clinicopathologic and imaging characteristics of 6 patients who were diagnosed as ipilimumab associated hepatitis during the ipilimumab treatment for melanoma. The clinical features of these patients were as follows: (1) severe cases with systemic symptoms and highly increased level of liver function tests (LFTs), and (2) mild asymptomatic cases with mildly increased level of LFTs. In severe cases with ALT >1,000 IU/L, imaging findings were characterized by mild hepatomegaly, periportal edema, and periportal lymphadenopathy, while mild cases showed normal imaging findings. This spectrum of imaging findings in our series was similar to that of common causes of acute hepatitis. Among 3 cases with pathologic specimen, two cases showed severe panlobular hepatitis with prominent perivenular infiltrate with endothelialitis, suggestive of predominant injury to hepatocytes, while the other case showed mild portal mononuclear infiltrate around proliferated bile ductules, suggestive of predominant injury to bile ducts. In summary, ipilimumab associated hepatitis may demonstrate variable imaging findings according to its clinical severity, and histologically may manifest either as a predominant injury to hepatocytes (acute hepatitis pattern) or as a predominant injury to bile ducts (biliary pattern).


Ipilimumab Hepatitis Immune-related adverse events Imaging Pathology 


Conflict of interest

All authors have nothing to disclose.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Kyung Won Kim
    • 1
    • 4
    Email author
  • Nikhil H. Ramaiya
    • 1
  • Katherine M. Krajewski
    • 1
  • Jyothi P. Jagannathan
    • 1
  • Sree Harsha Tirumani
    • 1
  • Amitabh Srivastava
    • 2
  • Nageatte Ibrahim
    • 3
  1. 1.Department of ImagingDana-Farber Cancer Institute, Brigham and Women’s HospitalBostonUSA
  2. 2.Department of PathologyBrigham and Women’s HospitalBostonUSA
  3. 3.Department of OncologyDana-Farber Cancer Institute, Brigham and Women’s HospitalBostonUSA
  4. 4.Department of Radiology and Research Institute of RadiologyUniversity of Ulsan College of Medicine, Seoul Asan Medical CenterSeoulKorea

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