Antibody-mediated rejection as a contributor to previously unexplained early liver allograft loss.

We analyzed 60 patients with idiopathic early allograft loss (defined as death or retransplantation at <90 days) to determine the relative contribution of preformed donor-specific human leukocyte antigen alloantibodies (DSAs) to this endpoint, and we defined strict criteria for the diagnosis of antibody-mediated rejection (AMR) in liver allografts. The inclusion criteria encompassed the availability of a pretransplant serum sample and both postreperfusion and follow-up tissue specimens for a blinded, retrospective re-review of histology and complement component 4d (C4d) staining. AMR was diagnosed on the basis of the presence of all 4 of the following strict criteria: (1) DSAs in serum, (2) histopathological evidence of diffuse microvascular injury/microvasculitis consistent with antibody-mediated injury, (3) diffuse C4d staining in the portal microvasculature with or without staining in the sinusoids or central veins in at least 1 sample, and (4) the exclusion of other causes of a similar type of injury. Patients thought to be experiencing definite AMR on the basis of routine histopathology alone showed the highest levels of DSA sensitization. Forty percent of patients with pretransplant DSAs with a pattern of bead saturation after serial dilutions developed AMR. Another multiparous female developed what appeared to be a strong recall response, which resulted in combined AMR and acute cellular rejection (ACR) causing graft failure. A contribution of DSAs to allograft failure could not be excluded for 3 additional patients who received marginal grafts. In conclusion, liver allograft recipients with preformed DSAs with a high mean fluorescence intensity despite dilution seem to be at risk for clinically significant allograft injury and possibly for loss from AMR, often in combination with ACR.

Implications of a positive crossmatch in liver transplantation: a 20-year review.

Whether a positive crossmatch result has any relevance to liver transplantation (LT) outcomes remains controversial. We assessed the impact of a positive crossmatch result on patient and graft survival and posttransplant complications. During a 20-year period, 2723 LT procedures with crossmatch results were identified: 2479 primary transplants and 244 retransplants. The rates of positive B cell and T cell crossmatches were 10.1% and 7.4%, respectively, for primary transplants and 14.6% and 6.4%, respectively, for retransplants (P = 0.049 for a B cell crossmatch). Across all primary transplants, females (P < 0.001) and patients with autoimmune hepatitis (P < 0.001) had greater frequencies of positive crossmatches. There was no effect from race or age. For both primary transplants and retransplants, patient survival and graft survival were not affected by the presence of a positive crossmatch. With respect to posttransplant complications, there were no differences in rejection episodes (hyperacute, acute, or chronic) or technical complications (biliary and vascular) between negative and positive crossmatch groups. However, there were significant differences in the pathological findings of preservation injury (PI) on liver biopsy samples taken at the time of transplantation and within the first week of transplantation (P = 0.003 for B cells and P = 0.03 for T cells). In summary, a positive crossmatch had no significant impact on patient survival or graft outcomes. However, there was a significantly higher incidence of PI in primary LT recipients with a positive crossmatch. This finding is important for a broader understanding of PI, which may include a significant immunological component.

The changing clinical presentation of recurrent primary biliary cirrhosis after liver transplantation.

BACKGROUND: Recurrent disease after liver transplant is a significant problem. Recurrent primary biliary cirrhosis (RPBC) is a histologic diagnosis. Clinical data is unreliable in predicting or diagnosing recurrence. RPBC appears to have a changing clinical presentation in recent years. MATERIALS AND METHODS: The diagnosis of RPBC after liver transplantation was made histologically. Data were obtained from our prospectively maintained liver-transplant database and evaluated statistically. RESULTS: Between 1985 and 1999, 1,835 liver transplants were performed, 169 for PBC. One hundred fifty-six patients were evaluated (one patient received retransplantation, and 13 were excluded). Seventeen (10.9%) experienced recurrence. Median posttransplantation follow-up time was 72.1 months. Median time to recurrence was 49.6 months. Median follow-up time after recurrence was 11.5 months. Neither acute rejection episodes (P=0.34) nor OKT3 use (P=0.36) before diagnosis of recurrence was significant. The combination of cyclosporine, azathioprine, and prednisolone demonstrated recurrence in 6 of 71 (8.4%). Six of 49 (12.2%) patients treated with cyclosporine with or without mycophenolate mofetil and prednisolone experienced recurrence. Six of 36 (16.7%) patients treated with tacrolimus and prednisolone with or without mycophenolate mofetil experienced recurrence. Patients treated with cyclosporine had numerically fewer recurrences than those treated with tacrolimus (P=0.11). CONCLUSIONS: Patients with RPBC demonstrated prolonged survival. Clinical factors did not aid in predicting RPBC. The clinical course of RPBC appears to be different than in the earlier years of liver transplantation. Immunosuppression may play a role. The use and type of antimetabolite drugs had no affect on recurrence. RPBC demonstrated a different clinical course with tacrolimus treatment (shorter time to recurrence) and increased incidence when compared with cyclosporine treatment. Controlled randomized studies are necessary to determine differences between tacrolimus and cyclosporine treatment, if any.