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

The study 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 7 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 [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 versus mild/moderate steatohepatitis (4.0 [3.0-4.6] versus 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 3 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.