Conversion From Once-Daily Prolonged-Release Tacrolimus to Once-Daily Extended-Release Tacrolimus in Stable Liver Transplant Recipients.

OBJECTIVES: After organ transplant, strategies to simplify the therapeutic regimen may improve adherence and prevent rejection and/or graft loss. The aim of the present study was to evaluate the safety of conversion from once-daily prolonged-release tacrolimus (Advagraf; Astellas Pharma Europe Limited, Middlesex, UK) to once-daily extended-release tacrolimus (Envarsus; Chiesi SAS, Nanterre, France) in stable adult liver transplant recipients. MATERIALS AND METHODS: This observational study inclu-ded 44 liver transplant patients (median age of 59 y; 63.6% men; median delay after transplant of 72.5 mo). Conversion was based on a 1:0.70 proportion. RESULTS: Mean dose of tacrolimus was 2.65 ± 1.24 mg/day before conversion and 2.09 ± 1.68 mg/day after conversion (P < .05), with ratio of 1:0.79. Mean serum tacrolimus trough level increased after conversion (4.92 ± 1.65 vs 5.60 ± 2.89 ng/mL; P < .05), with ratio of 1:1.14. Six months after conversion, mean dose of tacrolimus was 1.65 ± 0.93 mg/day (ratio of 1:0.62) and mean serum tacrolimus trough level was 4.82 ± 1.85 ng/mL, similar to the initial level before conversion. At the end of follow-up, 2 patients had returned to once-daily prolonged-release tacrolimus because of adverse effects (allergy, digestive trouble), which resolved thereafter. The mean cost of tacrolimus therapy was 5.54 ± 2.29 Euros/patient/day before conversion and 4.11 ± 2.32 Euros/patient/day after conversion (P < .05). CONCLUSIONS: Conversion from prolonged-release to extended-release tacrolimus in stable liver transplant patients is safe and cost-effective; however, initially, dose adaptations and careful monitoring are required.

Immunosuppression in hepatitis B virus and hepatitis C virus transplants: special considerations.

The management of the immunosuppression treatment must take account its consequences on viral replication. Such treatment operates on the emerging balance between the recurrence of the virus on the graft and the immune response of the host. Randomized and prospective trials are currently ongoing with the purpose of determining the opportunity and relevance of each immunosuppressive agent in the treatment. In HBV patients, good control of HBV reinfection by prophylactic strategies using HBIG, lamivudine, or both have decreased the impact of immunosuppression on HBV recurrence. In contrast, HCV recurrence is now a major problem. The mechanisms of viral recurrence need to be deepened thus requiring new studies. The absence of in vitro and in vivo systems to study HCV reinfection is a lack in the comprehension of the relation between HCV and immunosuppression. It will allow adapting the effectiveness of the immunosuppression treatment. The treatment's primary target is to avoid graft rejection, and its secondary objective is to limit the risk of viral recurrence.

Activation of NF-kappa B, AP-1 and STAT transcription factors is a frequent and early event in human hepatocellular carcinomas.

BACKGROUND/AIMS: Hepatitis B and C viruses, two inducers of hepatocarcinomas, have been shown to activate AP-1, NF-kappa B and STAT in vitro, but no detailed information on the activity of these transcription factors in vivo have been provided. METHODS: We have measured the DNA binding activity of these transcription factors in the peri-tumoral and the tumoral parts of 15 primary liver cancers, of viral or non-viral etiologies, and in five hepatic metastases using electrophoretic mobility shift assays. RESULTS: AP-1, NF-kappa B and STAT binding activities were increased in the peritumoral tissue, compared with histologically normal livers in 73, 87 and 70%, respectively, of the cases. A further activation of AP-1, NF-kappa B, but not STAT binding in the tumoral parts was detected in 40 and 80%, respectively, of the cases. A close correlation was found between JunD and c-Jun levels and AP-1 binding activity at the tumoral stage. By contrast, AP-1 and NF-kappa B binding activities were low or only slightly elevated in the peri-tumoral and the tumoral tissue of metastases. CONCLUSIONS: Early activation of AP-1, NF-kappa B and STAT contributes probably to the acquisition of a transformed phenotype during hepatocarcinogenesis, whatever the etiology.