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

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.

Keywords: 111In-labelled leucocytes; alcohol-related liver disease; cirrhosis; inflammation; liver biopsy; steatohepatitis.