Long-term results of mycophenolate mofetil as part of immunosuppressive induction therapy after liver transplantation.

BACKGROUND: The addition of mycophenolate mofetil (MMF) to the induction protocol resulted in a lower incidence of rejection episodes. However, the question whether MMF should be administered in combination with tacrolimus or cyclosporine has not been answered yet. In our study, we report on the long-term results of triple induction therapy after orthotopic liver transplantation (OLT), consisting of MMF and low-dose corticosteroids, in combination with either tacrolimus or cyclosporine. METHODS: Between March 1996 and April 1997, 120 consecutive patients, who underwent OLT at our institution, were enrolled in this study. Of these patients, 80 received triple induction therapy consisting of cyclosporine and MMF (40) or tacrolimus and MMF (40), in combination with low-dose corticosteroids, whereas the remaining 40 patients served as 'MMF-free' control group receiving dual induction therapy with tacrolimus and corticosteroids. Besides the eight-yr follow-up of patient and graft survival, clinical data were also reviewed for episodes of rejection and infection. Additionally, the early post-operative pharmacokinetics of mycophenolic acid (MPA, immunological active metabolite of MMF) were evaluated. RESULTS: Long-term results provided higher patient and graft survival after tacrolimus/MMF-based induction therapy than after cyclosporine/MMF-based induction therapy. However, the tacrolimus-based control protocol yielded similar results and, therefore, no significantly superior effect was observed when MMF was added. The same observation was made for incidence of rejection and infection episodes. AUC and C(max) of MPA increased in combination with tacrolimus compared with cyclosporine. CONCLUSIONS: Although pharmacological synergy between tacrolimus and MMF was observed, MMF showed no significant beneficial effects in the immunosuppressive induction protocol, neither in combination with tacrolimus nor with cyclosporine.

Increased mortality after liver transplantation for hepatocellular carcinoma in hepatitis B-associated cirrhosis.

Transplant patients suffering from hepatocellular carcinoma in cirrhosis are selected according to tumor nodule number and diameter. Vascular invasion and histopathological grading are predictive of outcome. The prognostic influence of hepatitis B-cirrhosis has been investigated after resection and after local tumor treatment, but not after transplantation. Of the 1,188 transplantations performed between 1989 and 2000, 120 were on patients with hepatocellular carcinoma in cirrhosis (HCC) (follow-up: 57 months; 1-140 months). Within this group, 25 patients (21%) suffered from hepatitis B. Pre-transplant selection criteria were a maximum diameter of 5 degrees cm in uni-nodular tumors, or 3 degrees cm for two to three tumor nodules. The rate of tumors with 2-3 tumor nodules was increased in the hepatitis-B group (52% vs. 29%; P<0.05). Other tumor characteristics did not differ. In the hepatitis-B group, more patients died post-transplantation (44% vs.22%; P<0.05). This difference was due to unspecific causes, not to tumor recurrence or re-infection. These findings may be indicative of a more complicated course in patients suffering from hepatitis B in general.

Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis.

Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.

Magnetic resonance imaging of inflammatory bowel disease: evaluation in a rabbit model.

PURPOSE: To correlate intestinal contrast enhancement and wall thickening with the degree of inflammation in an experimental model of inflammatory bowel disease. MATERIALS AND METHODS: Inflammatory bowel disease was elicited in 39 New Zealand White rabbits by rectal instillation of 2,4,6-trinitrobenzene sulphonic acid (TNBA). Magnetic resonance imaging (MRI) was used to determine bowel wall thickness and intestinal contrast enhancement after the administration of 0.1 mmol/kg of gadodiamide intravenously. MR measurements were compared with the complete histopathologic analysis. RESULTS: MR measurements of bowel wall thickness correlated well with histopathologic measurements in vitro (r = 0.85, P < 0.0001) and with histopathologic evidence of chronic inflammatory bowel disease (P < 0.02). Chronic inflammation was characterized by increased intestinal contrast enhancement (137 +/- 25%) when compared to normal bowel (86 +/- 7%, P = 0.04). CONCLUSION: Contrast-enhanced MRI accurately reflects inflammatory bowel disease in the rabbit model.