title: Early graft loss secondary to massive hemorrhagic necrosis following orthotopic liver transplantation. Evidence for cytokine-mediated univisceral Shwartzman reaction.
abstract: Massive hemorrhagic necrosis (MHN) of the liver following orthotopic liver transplantation (OLT) occurs infrequently during an otherwise uneventful recovery 1 week after OLT. It is characterized by fever and sudden deterioration of allograft function leading to failure in the absence of vascular thrombosis. The etiology is unknown, although it is usually preceded by some degree of allograft rejection. Between 6 and 8 days after OLT, four patients (out of 150) became febrile, hypotensive, and experienced a rapid rise in transaminases within 48 hr. Two patients had evidence of mild rejection; the other two had moderate to severe acute cellular rejection. All patients were ABO identical, crossmatch negative. Bolus steroids were given followed by OKT3 in the two patients with severe rejection. Although sepsis was suspected, antibiotic therapy did not ameliorate the clinical course. Each patient progressed to MHN with severe centrilobular necrosis and variable portal infiltrate. High levels of interferon-gamma and tumor necrosis factor-alpha occurred prior to the rise in transaminases in each MHN patient (155 +/- 39 pg/ml and 414 +/- 201 pg/ml, respectively) compared with levels in OLT patients with severe rejection (14 +/- 4 pg/ml and 26 +/- 5 pg/ml, respectively, P < 0.05). These data support the concept of a cytokine-mediated inflammatory response leading to a univisceral Shwartzman reaction in the transplanted liver. Early recognition of this syndrome and retransplantation are critical for survival.
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Florida 33136, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Burke
authors.forename: R
authors.initials: R
authors.lastname: Cirocco
authors.forename: A
authors.initials: A
authors.lastname: Viciana
authors.forename: P
authors.initials: P
authors.lastname: Ruiz
authors.forename: M
authors.initials: M
authors.lastname: Markou
authors.forename: M
authors.initials: M
authors.lastname: Allouch
authors.forename: G
authors.initials: G
authors.lastname: Ciancio
authors.forename: R
authors.initials: R
authors.lastname: Reddy
authors.forename: L
authors.initials: L
authors.lastname: Jeffers
authors.forename: E
authors.initials: E
authors.lastname: Schiff
authors.forename: J
authors.initials: J
authors.lastname: Nery
authors.forename: J
authors.initials: J
authors.lastname: Miller
authors.forename: A G
authors.initials: AG
authors.lastname: Tzakis
mesh_terms: D000328:Adult; D005260:Female; D006085:Graft Survival; D006470:Hemorrhage / Q000209:etiology; D006509:Hepatitis B / Q000601:surgery; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000473:pathology; D008103:Liver Cirrhosis / Q000601:surgery; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D013997:Time Factors