Baas, M. (Marjolein) (2014) Histologie van de lever vijf jaar na levertransplantatie bij kinderen, met als belangrijkste immunosuppressieve medicatie Tacrolimus. thesis, Medicine.
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Abstract
Background: Pediatric liver transplantation is a relative new treatment option for children with end-stage liver failure. Due to a constant optimisation of the post-transplant care there is already a 10-year survival described of more than 80%. Despite these good reports there is one big disadvantage for pediatric liver transplantation: there is still very little known about the histological findings in the transplanted liver and the association of those findings with future function of the transplanted liver graft. Many studies have shown that in time after liver transplantation more histological abnormalities are found in the grafts. These abnormalities are mainly fibrosis and chronic hepatitis. The cause of these abnormalities is still unknown and also the clinical consequences of those histological findings are not yet fully understood. It is thought that these abnormalities perhaps have a negative influence on the long term function of transplanted liver. Questions: The purpose of this study was to review histological abnormalities that are seen after liver transplantation by using the protocol biopsies that are taken at one and five years post transplantation. We looked for answers to the following questions: - Do these biopsies show fibrosis or other histological abnormalities and do these abnormalities progress in time after transplantation in patients who use Tacrolimus (TAC)? - Is the prevalence and severity of portal fibrosis with the use of TAC comparable to the prevalence and severity of fibrosis with the use of Cyclosporine (CsA)? - Is there an increase of decrease in the prevalence of histological hepatitis five years after liver transplantation using TAC? - Is there an association between pre-transplantation, transplantation and/or post-transplantation-related factors and portal fibrosis five years after transplantation? Patients and Method: In this retrospective study we included all patients who underwent a liver transplantation between 1999 and 2008, had a protocol biopsy at one and five years after transplantation, and used TAC as immunosuppressive. In total 51 patients were included. Retrospective all patients files were searched for data of pre- and post-transplantation related factors. All data was processed and analysed by using IBM SPSS Statistics 20. For the continuous variables the Mann-Whitney-U test or t-test were used, for the categorical variables the Pearson’s chi-squared test or Fisher’s exact test. Results: The prevalence of fibrosis increased from 45% after one year to 67% after five years and was significantly often seen in the fifth year biopsy when already fibrosis was present in the first year biopsy (p=0.005). Also the stage of fibrosis at the fifth year biopsy was significantly more severe in the patients who already showed fibrosis after the first year (p=0.024). The prevalence of histological hepatitis decreased from 14% after one year to 2% after five years. Minimal reactive changes (portal and/or parenchymal inflammation) were present in 29% after the first year in respect of 35% after five years and appeared significantly often with fibrosis than biopsies without minimal reactive changes (p=0.046). Male gender appeared to be a predisposed factor for the development of fibrosis (p=0.019), even as a CMV positive status at times of the liver transplantation. No relation has been found between transplantation and/or follow up related factors and the presence of fibrosis. Conclusion: In this retrospective study we showed that there is an increase in the prevalence and severity of fibrosis five year after pediatric liver transplantation with use of TAC, in comparison to one year post transplantation. These outcomes are comparable to earlier reported results with the use of CsA. Minimal reactive changes seem to play an important role in the development of fibrosis. Although it is still unclear if fibrosis will eventually lead to graft failure. Future research needs to be done to elucidate the clinical consequences of fibrosis and minimal reactive changes.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Scheenstra, dr. R. and Universitair Medisch Centrum Groningen and Kindergastro-enterologie |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:44 |
| Last Modified: | 25 Jun 2020 10:44 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/564 |
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