Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease

Background: Liver disease is often characterized by the activation of coagulation and inflammation. Experimental studies suggest that the interaction between neutrophils and platelets with local activation of coagulation could contribute to liver injury progression, but there have been limited studies in humans. 

Objectives: We studied the hemostatic components and neutrophil extracellular traps (NETs) in liver biopsies from patients with different inflammatory liver diseases. 

Methods: Liver biopsies from patients with inflammatory liver disease (alcoholic steatohepatitis [ASH], autoimmune hepatitis, primary sclerosing cholangitis, metabolic-associated steatohepatitis, and allograft ischemia-reperfusion injury (IRI), each n = 20) were stained for fibrin(ogen), platelets, and NETs. The correlation of NET formation with deposition of hemostatic components and laboratory measures of disease severity was investigated. 

Results: In 75% of the liver biopsies, no fibrin(ogen) was detectable, and only 20% of the biopsies showed minimal deposition. Overall, 50% of liver biopsies stained positive for NETs. Platelet deposition and NET formation were highest in IRI, where it correlated with histologic severity of injury (r = .61 [95% CI, .22-.84]; P < .01) and ASH. Platelet deposition was associated with NET formation (r = .44 [95% CI, .27-.59]; P < .001) and colocalized in the biopsies. NET formation, but not fibrin and platelet deposition, was moderately associated with the model of end-stage liver disease score (r = .29 [95% CI, .07-.49]; P < .01). 

Conclusion: In contrast to experimental studies, we demonstrated minimal intrahepatic fibrin(ogen) deposition in different types of human inflammatory liver disease. Histologic evidence for intrahepatic NETs was common and most pronounced in acute ASH and IRI and was associated with platelet deposition and disease severity.