Prof. Song Shibing
What acute rejection: man has the ability to protect himself from foreign matters, such as virus, bacteria, it is called immunity. The transplant allo-liver is also a kind of foreign matter. The attack of immunity to the donor liver will cause acute rejection. Without immunosuppressant, acute rejection will surely arise in non-relative allotransplant on the 7th~14th day after operation.
Type of acute rejection: super-acute rejection, acute rejection, chronic rejection.
Super-acute rejection: less frequent, occurs shortly after operation. Because of non-match of ABO blood type, multiple pregnant, retransplantation, etc.
Acute rejection: happens on the 7th~14th day after operation. Clinical presentations, fever, inappetency, jaundice, decreased bile volume, increasing transaminase. Liver biopsy is helpful and accurate for diagnosis.
Chronic rejection: happening time variable, no specific clinical presentation, progressive liver failure, retransplant needed.
Immunosuppressant: ①calcineurin inhibitor: CsA, FK506 ② antiproliferation agents: CellCeft, azathioprine ③glucocorticosteriods: methylprednisolone, prednisone ④multi-, mono-crone antibodies: Zenapax
Calcineurin inhibitor is the main immunosuppressant, may used solely or together with others. Combination use of immunosuppressant may decrease the dosage of any one immunosuppressant so that lessen the side effect the immunosuppressant.
Immunosuppressive treatment: ①induction: early phase post-OLT, mainly methylprednisolone ②maintenance: keep blood concentration of immunosuppressant at certain level ③remedy treatment: increasing dosage, immunosuppressant alteration, large dosage of methylprednisolone
Regimen: differs in every center. Usually triple combination use: CsA or FK506 + CellCeft or Aza + prednisone
Monitor of blood concentration: regularly, individualization. According to patients' liver function, side effect, ect.
Concentration of FK506,
Dosage decreasing: dosage can be decreased when the patient's condition is stable, to maintenance level. Steriods can be stopped 4~6 months post-OLT.
Individualization and flexibility is the ideal target for the use of immunosuppressants.
Immunosuppressants of the same type (such as CsA and FK506) can not be applied at the same time. Definitely, no contraindications for other medicine during the use of immunosuppressants.
Prograf (FK506): lipid can increase the adoption. Take before other foods. Can aggravate the kidney and neurological side effect when taking with antibiotics, anti-fungi medicine, anti-virus medicine. Increasing blood potassium level with taking with spironolactone, triamterene.
Medicine decreasing blood concentration of FK506: phenobarbital, Rifampin,isoniazid,etc.
Medicine increasing blood concentration of FK506: fluconazol, ketoconazol, erythromycin, roxithromycin, Losec, lidocaine, quinidine, verapamil.
CsA: stable absorption for microemulsion No influence from bile secretion. Kidney toxicity aggravated when used with aspirin, diclofenac, ibuprofen. May cause poisoning of digitoxin.
CellCeft: food taking has no influence on absorption rate. But peak concentration decreased. Medicines increasing concentration: acyclovir, probenecid.
Glucocorticoids: cause peptic ulcer when taking with aspirin.
Dichlothiazide: aggravate carhydrate tolerance abnormality.
Side effects of immunosuppressants:
Prograf: hyperlipidemia, leukopenia, thrombocytopenia, oral ulcer, joint disease.
CsA: kidney impairment, hypertrichosis, gingival hypertrophy, hypertension, tremor.
CellCeft： leukopenia, digestive tract hemorrhage, diarrhea, vomiting, kidney impairment, hyperlipidemia.
glucocorticoid: water and natrium retension, hypertension, Cushing's face, irregular menstruation, glaucoma, osteoporosis, headache, peptic ulcer.
Common problems concerning long-term use of immunosuppressants.
1 Alter the type of the dosage of immunosuppressants freewheelingly: orders from the doctors should be obeyed. Don't believe others advice credulously. The communication between patients is important, but should remember the individual difference for the use of immunosuppressant.
2 Alter the time of medicine taking freely: Prograf should be taken before food taking, or 1 hour before dining, or 2~3 hours after dining. The blood sample for the exam of blood concentration should be drew before medicine taking.
3 Question of immunosuppressant withdrawal: liver is the immunity preferential organ. There are examples that immunosuppressant was completely withdrew for long-term survival patients. Acute rejection will not take place in about 30% of patients, and well liver function can be maintained for at least 5 years. The current policy: decrease the dosage as much as possible, maintain the lowest concentration that can protect the donor liver.
4 Usage of steroids: opinions differ, in the era of FK506 as the basic immunosuppressant, especially for liver transplant patients, the main trend is to withdraw steroids as soon as possible. Or with the combination use of FK506 and MMF, steroid is only used in the operation. And withdraw it 3 months after the operation.