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

• Published in: Bioscience reports Vol. 38; no. 4
• Main Authors: Potts, Jonathan R, Farahi, Neda, Howard, Mark R, Taylor, Mark R, Heard, Sarah, Shankar, Arun N, Alexander, Graeme J, Chilvers, Edwin R, Verma, Sumita, Peters, A Michael
• Format: Journal Article
• Language: English
• Published: England 31-08-2018
• Subjects: Acute Disease; Adult; Cell Movement; Female; Hepatitis, Alcoholic - diagnostic imaging; Hepatitis, Alcoholic - immunology; Hepatitis, Alcoholic - pathology; Humans; Indium Radioisotopes - analysis; Liver - diagnostic imaging; Liver - immunology; Liver - pathology; Male; Middle Aged; Neutrophil Infiltration; Neutrophils - immunology; Neutrophils - pathology; Radionuclide Imaging; steatohepatitis; 111In-labelled leucocytes; alcohol-related liver disease; inflammation; liver biopsy; cirrhosis
• ISSN: 1573-4935
• DOI: 10.1042/BSR20180466

The study's aim was to image severe alcoholic hepatitis (SAH) using
In-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.
In-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
Tc-nanocolloid scintigraphy. Change in hepatic
In 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
In-leucocytes was performed in one patient. Median 24 h:30 min hepatic
In 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,
<0.0001). In SAH, it correlated with CD15 expression (r = 0.62,
=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),
=0.006). Hepatic-to-splenic
Tc 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);
=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
In in areas of parenchymal neutrophil infiltration. In conclusion,
In-leucocyte scintigraphy can non-invasively diagnose SAH and could provide a platform for evaluation of novel treatments aiming to inhibit intrahepatic neutrophil migration.