Approaching treatment for immunological rejection of living-donor liver transplantation in rats
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Published on: November 7, 2020
Yanhu Feng1, Zhijian Han2, Zedong Feng3
1Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, 730030, China.
Background:
The anti-immunological rejection therapy for small-for-size syndrome (SFSS) after live donor liver transplantation (LDLT) play a central role in keeping graft survival. The hepatocyte number and grafts function has undergone real-time changes with the proliferation and apoptosis of the grafts after reperfusion. Lacking an accurate and effective treatment regiments or indicators to guide the use of immunosuppressive drugs in SFS liver transplantation has made immunotherapy after SFS liver transplantation an urgent problem to be solved. Herein, we established small-for-size (SFS) and normal size liver transplantation model in rats to explore the effective indicators in guiding immunotherapy, to find an effective way for overcoming SFSS.
Methods:
Lewis rats (donors) and BN rats (recipients) were used to mimic allograft liver transplantation and treated with tacrolimus. Local graft immune response was analyzed through haematoxylin and eosin and immunohistochemistry. Flow cytometry was used to assess the overall immune status of recipient. The pharmacokinetics mechanism of immunosuppressive drugs was explored through detecting CYP3A2 expression at mRNA level and protein levels.
Results:
The results showed the local immune reaction of SFS grafts and systemic immune responses of recipient were significantly increased compared with those in normal size grafts and their recipient at four days after liver transplantation. Regression equation was used to regulate the tacrolimus dose which not only controlled tacrolimus serum concentration effectively but alleviated liver damage and improved survival rate.
Conclusions:
This study showed that AST level and tacrolimus serum concentrations are effective indicators in guiding immunotherapy. Regression equation (TD = - 0.494TC-0.0035AST + 260.487) based on AST and tacrolimus serum concentration can be used as a reference for adjustment of immunotherapy after SFS liver transplantation, which is applicable in clinical practice.
Insights
Small-for-size syndrome (SFS) liver transplantation requires better immunotherapy. AST levels and tacrolimus serum concentrations effectively guide immunosuppression, improving graft survival in SFS liver transplants.
Area of Science:
- Transplantation immunology
- Graft survival optimization
- Immunosuppressive drug management
Background:
- Small-for-size syndrome (SFS) poses challenges in live donor liver transplantation (LDLT), impacting graft survival due to dynamic hepatocyte changes.
- Current immunotherapy lacks precise indicators for guiding immunosuppressive drug use in SFS liver transplantation.
- Developing effective strategies to overcome SFSS is crucial for successful LDLT.
Purpose of the Study:
- To establish rat models for small-for-size (SFS) and normal size liver transplantation.
- To identify reliable indicators for guiding immunotherapy in SFS liver transplantation.
- To develop an effective approach for managing SFSS.
Main Methods:
- Utilized Lewis and BN rats for allograft liver transplantation models, administering tacrolimus.
- Analyzed local graft immune response via histology and immunohistochemistry.
- Assessed recipient immune status with flow cytometry and explored drug pharmacokinetics by detecting CYP3A2 expression.
Main Results:
- SFS grafts exhibited significantly increased local immune reactions and recipient systemic immune responses compared to normal size grafts.
- A regression equation effectively regulated tacrolimus dosage, controlling serum concentration.
- Tacrolimus dose adjustment alleviated liver damage and improved survival rates.
Conclusions:
- Aspartate aminotransferase (AST) levels and tacrolimus serum concentrations serve as effective indicators for guiding immunotherapy.
- A regression equation incorporating AST and tacrolimus levels provides a reference for adjusting immunotherapy post-SFS liver transplantation.
- The proposed regression equation is applicable in clinical settings for optimizing SFS liver transplant outcomes.
