Administration of granulocyte colony stimulating factor after liver transplantation leads to an increased incidence and severity of ischemic biliary lesions in the rat model

Table 1 Histologic damage score of the liver after liver transplantation

Single cell necrosis	0: No necrotic hepatocyte in 5 HPF (40 X)
	1: 1-10 in 5 HPF
	2: > 10
Confluent necrosis	0
	1: Small in size and number
	2: Large size and /or large number
Hepatic mitosis	0: No mitotic hepatocyte in 5 HPF (40 X)
	1: 1-10 in 5 HPF
	2: > 10 (extensive)
Bile duct inflammation damage	0: No inflammation;
	1: A minority of the ducts are cuffed and infiltrated by inflammatory cells
	2: More than an occasional duct showing degenerative changes or focal degenerative changes; Most of the ducts infiltrated by inflammatory cells
	3: Most of the ducts showing luminal disruption, most of the ducts infiltrated by inflammatory cells
Ductular proliferation	0: None
	1: Minimal (small proliferation in a minority of portal tracts)
	2: Mild (most portal tracts but not involving the lobular parenchyma)
	3: Moderate (all portal tracts and extending along the fibrous septa)
	4: Severe (extending along the portal tracts and also slightly involving the lobular parenchyma)
	5: Very severe (diffuse proliferation in the lobular parenchyma)
Fibrosis	0: None
	1: Fibrosis slightly extending portal tracts
	2: Fibrosis extending portal tracts with incomplete septa
	3: Fibrosis with complete septa bridging portal to portal tracts
	4: Incomplete (focal) or complete cirrhosis
Activated Kupffer cells	0: No activated Kupffer cells
	1: Activated Kupffer cells
Eosinophilic globuli	0: No eosinophilic globuli
	1: 1%-5% of all hepatocytes
	2: > 5%
Small vacuolar transformation of the cytoplasm	0: No small vacuolar transformation of the cytoplasm
	1: 1%-30% of all the hepatocytes
	2: > 30%

Table 2 Blood levels of ALT, AST and AP in rats after liver transplantation with and without G-CSF treatment

	24 h		1 wk		12 wk
Group	Untreated	G-CSF	Untreated	G-CSF	Untreated	G-CSF
ALT (u/L)	616 ± 1941	418 ± 731	192 ± 49	148 ± 81	92 ± 84	49 ± 24
AST (u/L)	344 ± 204	204 ± 48	96 ± 81	59 ± 28	35 ± 15	24 ± 13
AP (u/L)	141 ± 222	455 ± 992	453 ± 147	449 ± 418	473 ± 543	221 ± 68

¹ Significant difference between two groups (P < 0.05, t-test);

² Significant difference between two groups (P < 0.001, t-test).

Table 3 Signs of a hypercoaguable state after G-CSF treatment in healthy volunteers and in patients with G-CSF producing tumors

Author	n	Observations after G-CSF administration or in patients with G-CSF producing tumors
Topcuoglu et al, 2004[9]	18	Stimulation of thrombotic factors and increased endothelial markers, such as FVIII and vWF
		No clinical silent microembolism detected by transcranial Doppler
Sohngen et al, 1998[13]	25	Hypercoaguable state
LeBlanc et al, 1999[10]	22	Increased levels of FVIIIC and thrombin
		Reduced platelet aggregation.
Kuroiwa et al, 1996[12]	10	Significant increase of platelet aggregation induced by ADP or collagen, thromboxane B2 level and amount of thrombin-antithrombin III complex.
Canales et al, 2002[32]	20	Significant increase in F1 + 2 and D-dimer
		Significant decrease of antithrombin and protein C activity
		Significant increase of vWF
		Slightly significant decrease of angiotensin converting enzyme
Suzuki et al, 1992[33]	14	Thrombocytosis