Table 1.

Role of hemostatic system and fibrinogen in models of liver disease

Liver disease model	Activation of coagulation?a	Effects of hemostatic system modification on the liver disease?	Role of fibrinogen?	References
Hepatic ischemia/reperfusion	√	Anticoagulation: ↓ liver injury	Unknown	15, 25, 26
Lipopolysaccharide (LPS) administration	√	Thrombin inhibition: ↓ liver injury	Fibrinogen deficiency (ancrod): no effect on liver injury	12, 31
Ethanol/LPS co- exposure	√	Thrombin inhibition: ↓ liver injury PAI-1 deficiency: ↓ liver injury	Unknown	19,35
LPS-potentiated hepatotoxic responses	√	Thrombin inhibition: ↓ liver injury PAI-1 deficiency: ↓ liver injury	Unknown	23, 33, 34
Acetaminophen toxicity	√	Thrombin inhibition: ↓ liver injury PAR-1 deficiency: ↓ liver injury PAR-4 deficiency: ↓ liver injury PAI-1 deficiency: ↑ liver injury Plasminogen deficiency: ↓ liver injury	Fibrinogen deficiency (ancrod): no effect on liver injury Fibrinogen deficiency (Fga−/−): no effect on liver ALT levels	2, 20, 38, 39
Jo2-induced apoptosis	√	Thrombin inhibition: ↓ secondary liver necrosis Tissue factor deficiency: ↓ secondary liver necrosis	Unknown	10, 11
Acute cholestasis by alpha- naphthylisothiocyanate (ANIT)	√	Tissue factor deficiency: ↓ liver injury PAR-1 deficiency: no effect on liver injury	Fibrinogen deficiency (Fga−/−): ↓ liver injury	9, 50
Obstructive cholestasis by bile duct ligation (BDL)	√	PAI-1 deficiency: ↓ liver injury tPA deficiency: ↑ liver injury	Unknown	16, 17, 49
Acute carbon tetrachloride (CCl4) toxicity	√	Anticoagulation: ↑↓liver injury	Fibrinogen deficiency (Fga−/−): no effect on liver injury	8, 48, 64, 65
Chronic CCl4 toxicity	√	Anticoagulation:↓ liver fibrosis Factor V Leiden mutation: ↑ liver fibrosis PAR-1 deficiency: ↓ liver fibrosis PAR-2 deficiency:↓ liver fibrosis	Fibrinogen deficiency (Fga−/−): no effect on gross liver pathology	68, 69, 71, 72, 73
Cholestasis-associated fibrosis after BDL	√	Tissue factor deficiency: no effect on liver fibrosis Thrombocytopenia: ↓ liver necrosis Thrombocytopenia: ↑ liver fibrosis	Unknown	47, 76, 77
Cholestasis-associated fibrosis after chronic ANIT feeding	√	Tissue factor deficiency: ↓ liver fibrosis PAR-1 deficiency: ↓ liver fibrosis PAI-1 deficiency: ↑liver injury and liver fibrosis	Fibrinogen deficiency (Fga−/−): ↑liver injury	81, 82, 84, 86
Non-alcoholic fatty liver disease	√	Tissue factor/PAR-2 signaling: ↑ liver injury, steatosis, obesity Tissue factor deficiency: ↓liver injury, steatosis Thrombin inhibition: ↓ liver injury, steatosis, obesity PAR-1 deficiency: ↓liver injury, steatosis	Unknown	90, 91, 92, 93, 94

^aActivation of coagulation defined as evidence of thrombin generation, depletion of plasma fibrinogen, and/or thrombin-mediated hepatic fibrin(ogen) deposition