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In vivo imaging of hepatic neutrophil migration in severe alcoholic hepatitis with 111In-radiolabelled leucocytes.

Authors
  • Potts, Jonathan R1, 2
  • Farahi, Neda3
  • Howard, Mark R4
  • Taylor, Mark R4
  • Heard, Sarah5
  • Shankar, Arun N6
  • Alexander, Graeme J6
  • Chilvers, Edwin R4
  • Verma, Sumita1, 2
  • Peters, A Michael7
  • 1 Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospitals NHS Trust, Brighton, U.K.
  • 2 Department of Medicine, Brighton and Sussex Medical School, Brighton, U.K.
  • 3 Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, U.K.
  • 4 Department of Histopathology, Brighton and Sussex University Hospitals NHS Trust, Brighton, U.K.
  • 5 Department of Nuclear Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, U.K.
  • 6 Department of Hepatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, U.K.
  • 7 Division of Clinical and Laboratory Investigation, Brighton and Sussex Medical School, Brighton, U.K. [email protected]
Type
Published Article
Journal
Bioscience Reports
Publisher
Portland Press
Publication Date
Aug 31, 2018
Volume
38
Issue
4
Identifiers
DOI: 10.1042/BSR20180466
PMID: 29700216
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The study's aim was to image severe alcoholic hepatitis (SAH) using 111In-labelled leucocytes with two objectives in mind: firstly for non-invasive diagnosis and secondly to provide a platform for experimental therapies aiming to inhibit intrahepatic neutrophil migration. 111In-leucocyte scintigraphy was performed 30 min and 24 h post-injection in 19 patients with SAH, 14 abstinent patients with alcohol-related cirrhosis and 11 normal controls. Eleven with SAH and seven with cirrhosis also had 99mTc-nanocolloid scintigraphy. Change in hepatic 111In radioactivity was expressed as decay-corrected 24 h:30 min count ratio and, in SAH, compared with histological grading of steatohepatitis and expression of granulocyte marker, CD15. Hepatic microautoradiography on biopsy specimens obtained 24 h post-injection of 111In-leucocytes was performed in one patient. Median 24 h:30 min hepatic 111In activity ratio was higher in SAH (2.5 (interquartile range (IQR): 1.7-4.0) compared with cirrhotics and normal controls (1.0 (0.8-1.1) and 0.8 (0.7-0.9) respectively, P<0.0001). In SAH, it correlated with CD15 expression (r = 0.62, P=0.023) and was higher in marked compared with mild/moderate steatohepatitis (4.0 (3.0-4.6) compared with 1.8 (1.5-2.6), P=0.006). Hepatic-to-splenic 99mTc count rate ratio was reduced in SAH (0.5 (0.4-1.4)) compared with cirrhotics (2.3( 0.6-3.0)) and three historic normal controls (4.2 (3.8-5.0); P=0.003), consistent with impaired hepatic reticuloendothelial function. Scintigraphic findings in SAH included prominent lung radioactivity at 30 min, likely the result of neutrophil primimg. Microautoradiography demonstrated cell-associated 111In in areas of parenchymal neutrophil infiltration. In conclusion, 111In-leucocyte scintigraphy can non-invasively diagnose SAH and could provide a platform for evaluation of novel treatments aiming to inhibit intrahepatic neutrophil migration. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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