Liver biopsy findings in patients on immune checkpoint inhibitors.
Liver biopsy findings in patients on immune checkpoint inhibitors.
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DOI：
10.1038/s41379-020-00653-1
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Misdraji J
中科院分区：
文献类型：
--
作者：
Cohen JV;Dougan M;Zubiri L;Reynolds KL;Sullivan RJ;Misdraji J
免疫检查点抑制剂可以诱导对各种恶性肿瘤的持久反应，但可能导致免疫相关不良事件。免疫检查点抑制剂（ICI）相关肝炎通常表现为小叶炎症伴组织细胞、模糊至成形良好的肉芽肿、纤维蛋白环肉芽肿和内皮细胞增生。ICI胆管炎也有报道，这些患者可能有胆管扩张或梗阻性改变的影像学，和门静脉为基础的炎症与管道损伤。据报道，ICI相关胆管炎对类固醇的反应较低。本研究的目的是评估肝活检的炎症模式是否与LFT异常模式、影像学表现和对类固醇的反应性相关。确定了发生LFT升高并接受肝活检的患者。从电子记录中获得临床数据。对肝活检进行了审查，并将炎症模式记录为肝炎、胆管炎、脂肪变性或轻度非特异性变化。36例肝活检有肝炎炎症模式，包括16例肉芽肿和14例内皮炎。16例患者有胆管炎模式，伴门静脉炎症。4例患者各有类似脂肪肝或轻度非特异性变化的模式。两种最常见的组织学模式与LFT异常的模式相关。胆管炎型在肝脏影像学上更可能有胆管扩张或狭窄，2例患者最终被诊断为肿瘤引起的胆管梗阻。肝活检中的炎症模式、肉芽肿的存在或内皮细胞的存在并不能预测对类固醇的反应或是否需要二次免疫抑制。总之，我们发现，免疫检查点抑制剂患者的肝活检可能无法预测类固醇的需要，需要类固醇的时间长度，或需要二次免疫抑制。当LFT的模式是胆汁淤积时，可以看到胆管炎模式，但这种模式也可以在竞争药物反应或肿瘤引起的胆管阻塞中看到。
Immune checkpoint inhibitors can induce a durable response against a wide range of malignancies but may cause immune related adverse events. Immune checkpoint inhibitor (ICI) related hepatitis commonly shows lobular inflammation with histiocytes, vague to well-formed granulomas, fibrin ring granulomas, and endothelialitis. ICI cholangitis has also been reported and these patients may have bile duct dilatation or obstructive changes on imaging, and portal-based inflammation with duct injury. ICI related cholangitis is reportedly less responsive to steroids. The purpose of this study was to evaluate whether the pattern of inflammation on liver biopsy correlates with the pattern of LFT abnormalities, imaging findings, and responsiveness to steroids. Patient who developed elevated LFTs and underwent liver biopsy were identified. Clinical data was obtained from the electronic records. Liver biopsies were reviewed, and the pattern of inflammation was recorded as hepatitis, cholangitis, steatotic, or mild non-specific changes. Thirty-six liver biopsies had a hepatitis pattern of inflammation, including 16 patients with granulomas and 14 patients with endothelialitis. Sixteen patients had a cholangitic pattern, with portal-based inflammation. Four patients each had a pattern resembling fatty liver or mild nonspecific changes. The two commonest histologic patterns correlated with the pattern of LFT abnormalities. The cholangitic pattern was more likely to have bile duct dilatation or narrowing on liver imaging, and two patients were eventually diagnosed with bile duct obstruction from tumor. The pattern of inflammation, presence of granulomas, or presence of endothelialitis on liver biopsy did not predict response to steroids or the need for secondary immunosuppression. In conclusion, we found that a liver biopsy in patients on immune checkpoint inhibitors might not predict the need for steroids, the length of time that steroids is required, or the need for secondary immunosuppression. A cholangitic pattern may be seen when the pattern of LFTs is cholestatic, but this pattern can also be seen in competing drug reactions or bile duct obstruction from tumor.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
1.2
作者：
Kono, Masashi;Sakurai, Toshiharu;Kudo, Masatoshi
通讯作者：
Kudo, Masatoshi
影响因子：
6.2
作者：
Faje, Alexander T.;Lawrence, Donald;Sullivan, Ryan J.
通讯作者：
Sullivan, Ryan J.
影响因子：
5.6
作者：
Johncilla, Melanie;Misdraji, Joseph;Doyle, Leona A.
通讯作者：
Doyle, Leona A.
影响因子：
13.5
作者：
Kleiner, DE;Brunt, EM;Sanyal, AJ
通讯作者：
Sanyal, AJ