Ipilimumab associated hepatitis: imaging and clinicopathologic findings
Ipilimumab associated hepatitis: imaging and clinicopathologic findings
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DOI：
10.1007/s10637-013-9939-6
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发表时间：
2013-08-01
影响因子：
3.4
通讯作者：
Ibrahim, Nageatte
中科院分区：
文献类型：
--
作者：
Kim, Kyung Won;Ramaiya, Nikhil H.;Ibrahim, Nageatte
Ipilimumab是一种新型免疫调节剂，在治疗黑色素瘤和其他癌症方面显示出有希望的疗效。ipilimumab的临床获益可能受到宿主免疫系统失调引起的免疫相关不良事件（irAEs）的阻碍。易普利姆单抗相关性肝炎也是一种重要的irAE，然而，对其临床病理和影像学特征的描述有限。我们的目的是描述6例在伊匹单抗治疗黑色素瘤期间被诊断为伊匹单抗相关性肝炎的患者的临床病理和影像学特征。这些患者的临床特征为：(1)严重者有全身性症状，肝功能检查（LFTs）水平高升高；(2)轻度无症状者，肝功能检查（LFTs）水平轻度升高。重症患者影像学表现为轻度肝肿大、门静脉周围水肿、门静脉周围淋巴结病变，轻症患者影像学表现正常。在我们的系列中，这一系列的影像学发现与急性肝炎的常见病因相似。3例病理标本中，2例表现为重度全小叶性肝炎，静脉周围浸润明显伴内皮炎，提示肝细胞损伤为主；另1例表现为增生的胆管周围轻度门脉单核浸润，提示胆管损伤为主。总之，依匹单抗相关性肝炎可能根据其临床严重程度表现出不同的影像学表现，组织学上可能表现为肝细胞的主要损伤（急性肝炎型）或胆管的主要损伤（胆道型）。
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).