ETIOPATHOGENESIS AND PROGNOSIS OF CENTRILOBULAR NECROSIS IN HEPATIC GRAFTS

The incidence, contributing etiopathogenetic factors, and prognostic significance of centrilobular necrosis were investigated in 270 hepatic transplants to 215 immunosuppressed patients in whom 837 biopsies were performed. Twenty-six (9.6%) grafts demonstrated centrilobular necrosis in one or more biopsy specimens. The immunological, clinical, histopathological, and evolutionary features of this patient group (group A) were compared with a control group of patients who had undergone 92 consecutive transplants with no necrosis (group B). Group A was younger (p<0.01), had a higher average of warm and cold-ischemia time (p<0.05), a higher incidence (p<0.001) and earlier appearance of acute rejection episodes (p<0.01), and a closer association with evolution to chronic rejection (A: 53.8% vs B: 13.1%, p<0.001). Survival rates for grafts and patients with necrosis at 12 and 30 months were significantly lower (p<0.001). The 26 grafts were distributed into three chronological subgroups according to when necrosis appeared: (1) First week - All these grafts were lost (four through primary graft nonfunction and one due to portal recurrent thrombosis); (2) Second week - seven grafts with associated acute rejection, with three evolving to chronic rejection; (3) After the second week (116+/-82 days)- five with isolated necrosis, two with associated acute rejection, four with associated ductopenia, and three with associated acute rejection and ductopenia. In 11 grafts the necrosis persisted and evolved to chronic rejection. In conclusion, these findings indicate that centrilobular necrosis is a histopathological sign associated with poor prognosis in most hepatic grafts. Its association with greater donor-organ ischemia times and immunological changes may suggest a possible centrilobular ischemic etiology related to preservation problems and/or mediated by acute or chronic immune attack pathogenic mechanisms (endotheliitis and vasculapathy). (C) Journal of Hepatology.