Immunosuppression affects liver cancer recurrence after liver transplantation
Recurrence of liver cancer is a major factor affecting the long-term survival of liver transplant patients. In addition to the biological characteristics of the tumor, the reduced immune function of the body due to postoperative use of immunosuppressants and the weakened surveillance and killing effect on the tumor are among the important causes of tumor recurrence.
Thus, how to reduce the dosage of immunosuppressants and select the most appropriate immunosuppressant is an important measure to improve patient prognosis.
How should immunosuppression be used in liver transplant patients?
As research on the mechanisms of recurrence after liver transplantation for liver cancer continues, the strategy of immunosuppressant application has changed, mainly including:
- Assessment of individual immune function strength by Immunknow method monitoring (i.e., detection of a lymphocyte activity that is closely related to rejection). This method, combined with blood levels of immunosuppressants, can better guide post-transplant dose adjustments to minimize the use of immunosuppressants and reduce the risk of tumor recurrence in the absence of acute rejection.
- Detection of genetic polymorphisms of cytochrome P450 3A5 (CYP3A5), a key enzyme affecting the blood concentration of the anti-rejection drug tacrolimus, is mainly expressed in the liver and small intestine, and detection of CYP3A5 genetic polymorphisms in donors and recipients is important for the rational development of immunosuppressive regimens.
- Early withdrawal of hormones. By using bariximab preoperatively versus on postoperative day 4, followed by low-dose tacrolimus maintenance, hormone use can be discontinued at 1 month postoperatively, reducing the rate of tumor recurrence relative to the maintenance regimen of hormones after transplantation.
- Replacement of calcineurin inhibitors (cyclosporine and tacrolimus). Calmodulin inhibitors have the potential to increase the risk of recurrence after hepatocellular carcinoma transplantation. mTOR inhibitors (sirolimus and everolimus) are newly approved immunosuppressants with anti-lymphocyte proliferation, anti-tumor and antifungal effects, and have low nephrotoxicity, neurotoxicity, and the ability to reduce the incidence of diabetes and inhibit the growth and metastasis of hepatocellular carcinoma cells.
- Patients who meet the Milan criteria (i.e., no more than 5 cm in diameter for a single tumor or no more than 3 multiple tumors with a maximum diameter of 3 cm, no large vessel invasion, and no lymph node or extrahepatic metastases) may not be considered for replacement because of the low rate of postoperative recurrence and metastasis, provided that the tacrolimus dosage is kept as low as possible;
- For patients beyond the Milan criteria, a switch to sirolimus/ everolimus (alone or in combination with tacrolimus) is generally indicated 30 days after transplantation, given that the anti-angiogenic effect of mTOR analog inhibitors can affect wound healing.