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In the immunosuppression of orthotopic liver transplant recipients, steroids are used despite their unspecific action and long-term side effects. Few studies have been carried out on steroid withdrawal and many aspects remain to be elucidated.A prospective study was performed to analyse the effect of steroid withdrawal on 86 patients with stable graft function, more than 1 year after orthotopic liver transplant. Thirty patients had chronic hepatitis in the graft. Seventy-two continued with cyclosporine (CsA) and 14 with CsA-azathioprine (AZA) therapy. The follow-up was 23.2 +/- 8.1 months (range 12-52 months). A paired t-test was used for statistical analysis.No acute or chronic rejection occurred, and steroids were not reinstituted. There were no changes in serum transaminase levels, but bilirubin levels decreased (p0.01). At the end of the follow-up, we found improvements in blood pressure in hypertensive patients (systolic 156.1 +/- 8.4 mmHg vs. 139.4 +/- 8.7 mmHg, p0.001); body weight (72 +/- 13.5 kg vs. 70.8 +/- 13 kg, p0.05); serum cholesterol (211.3 +/- 42 mg/dl vs. 191.6 +/- 43.5 mg/dl, p0.001) and bone mineral density in lumbar spine (0.823 +/- 0.13 g/cm2 vs. 0.893 +/- 0.135 g/cm2, p0.001). Four of ten diabetic patients were no longer insulin-dependent and insulin requirements decreased in the remaining six. No significant biochemical changes were found in patients with hepatitis in the graft, and we found an improvement in inflammatory activity in the nine biopsied patients.Steroid withdrawal with CsA monotherapy is feasible, safe and beneficial in patients who have stable liver graft function 1 year after orthotopic liver transplant. We consider that AZA therapy is not necessary unless drastic reduction of CsA levels is required because of renal dysfunction.

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 protal 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.(ABSTRACT TRUNCATED AT 250 WORDS)