ETIOPATHOGENESIS AND PROGNOSIS OF CENTRILOBULAR NECROSIS IN HEPATIC GRAFTS

The incidence, contributing etiopathogenetic factors, and prognostic s ignificance of centrilobular necrosis were investigated in 270 hepatic transplants to 215 immunosuppressed patients in whom 837 biopsies wer e performed. Twenty-six (9.6%) grafts demonstrated centrilobular necro sis in one or more biopsy specimens. The immunological, clinical, hist opathological, 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 young er (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 reje ction episodes (p<0.01), and a closer association with evolution to ch ronic rejection (A: 53.8% vs B: 13.1%, p<0.001). Survival rates for gr afts and patients with necrosis at 12 and 30 months were significantly lower (p<0.001). The 26 grafts were distributed into three chronologi cal subgroups according to when necrosis appeared: (1) First week - Al l these grafts were lost (four through primary graft nonfunction and o ne due to portal recurrent thrombosis); (2) Second week - seven grafts with associated acute rejection, with three evolving to chronic rejec tion; (3) After the second week (116+/-82 days)- five with isolated ne crosis, two with associated acute rejection, four with associated duct openia, and three with associated acute rejection and ductopenia. In 1 1 grafts the necrosis persisted and evolved to chronic rejection. In c onclusion, these findings indicate that centrilobular necrosis is a hi stopathological sign associated with poor prognosis in most hepatic gr afts. Its association with greater donor-organ ischemia times and immu nological changes may suggest a possible centrilobular ischemic etiolo gy related to preservation problems and/or mediated by acute or chroni c immune attack pathogenic mechanisms (endotheliitis and vasculapathy) . (C) Journal of Hepatology.