Liver biopsy findings in patients on immune checkpoint inhibitors

Abstract

Immune checkpoint inhibitors (ICI) can induce a durable response against a wide range of malignancies but cause immune related adverse events. The purpose of this study was to evaluate whether the pattern of inflammation in a liver biopsy in patients on ICIs is likely to be related to ICIs or other causes, and whether the pattern correlates with LFT abnormalities, imaging findings, and responsiveness to steroids. Cancer patients on ICIs who underwent liver biopsy were identified. Clinical data were obtained from electronic records. Liver biopsies were recorded as hepatitic, cholangitic, mixed, steatotic, or as mild nonspecific changes. In total, 28 liver biopsies had a predominantly hepatitic pattern of inflammation, including 11 biopsies with granulomas and 10 with endothelialitis. Eight biopsies had a mixed hepatocytic and cholangitic pattern of injury, including 6 with granulomas and 4 with endothelialitis. Sixteen patients had a predominantly cholangitic pattern, with portal-based inflammation. Three patients had a pattern resembling fatty liver, and five had mild nonspecific changes. The three most common histologic patterns correlated with the pattern of LFT abnormalities. The majority of patients with a cholangitic pattern had competing causes for elevated LFTs, including disease progression or concomitant chemotherapy. The cholangitic pattern was more likely to have bile duct dilatation or narrowing on liver imaging. The pattern of inflammation, degree of lobular injury, or presence of granulomas or endothelialitis did not predict response to steroids or the need for secondary immunosuppression. In this retrospective study, the pattern of inflammation did not predict the need for steroids, the length of time that steroids is required, or the need for secondary immunosuppression. A cholangitic pattern was seen when the pattern of LFTs was cholestatic, and was associated with imaging abnormalities of the bile duct, but a similar pattern was seen in bile duct obstruction and other drug reactions.

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Fig. 1: Zone 3 hepatitis and necrosis with numerous histiocytes adjacent to an injured central vein.
Fig. 2: Medium power view of a liver biopsy with panlobular inflammation, but with focal area of necrosis in the lobule.
Fig. 3: Steatosis in an area of injury around a central vein with aggregates of histiocytes surrounding an injured vein.
Fig. 4: Fibrin ring granuloma in ICI hepatitis.
Fig. 5: An hepatic vein surrounded by mononuclear inflammatory cells and granulomatous inflammation (lower right).
Fig. 6: Liver biopsy in a patient with a cholangitic pattern and likely ICI-related cholangitis.
Fig. 7: Liver biopsy in a patient with a cholangitic pattern and disease progression in the liver causing bile duct compression, and likely contributing to the LFT abnormalities.
Fig. 8: Medium power view of a liver biopsy demonstrating a steatohepatitic pattern of injury.

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Correspondence to Joseph Misdraji.

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Cohen, J.V., Dougan, M., Zubiri, L. et al. Liver biopsy findings in patients on immune checkpoint inhibitors. Mod Pathol (2020). https://doi.org/10.1038/s41379-020-00653-1

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