Liver Transplantation Flashcards
Indications for liver transplant
- Synthetic failure: hypoalbuminemia, coagulopathy
- Encephalopathy
- Portal HTN: ascites, varieal bleeding, HPS
- Fatigue
- Life threatening infeciton
- Growth failure
Management of CLD prior to transplant
- Optimize nutrition, vitamins
- prevent infection, (SBP)
- monitor renal function,
- Avoid bentos and NSAIDS
- Treat ascites: albumin, diuretics, paracentesis
- Manage variceal bleeding
- Update vaccines
Indications that transplant is necessary
- Intractable ascites, severe encephalopathy, infx, FTT< HPS
Lab: coagulopathy, hypoalbuminemia, hypoglycemia, acidosis
Indications for liver transplant
Most common cause: BA
2nd most common cause: metabolic: A1AT, Wilsons’s PFIC
3rd: ALF
PELD score
- Age
- Bilirubin
- INR
- Albumin
- Growth
Contraindications
- Brain death
- Progressive multi-system dz
- extra-hepatic malignancy
- uncontrolled infection, AIDS
- Drug/alcohol abuse
- severe cardiopulmonary disease
- inability to comply with medical regimen
- anatomical abnormalities precluding transplant
- compensated cirrhosis without complications.
- portal vein thrombosis, cholangiocarcinoma, HIV, psych instability are relatives contraindications.
Facts to known about patient’s liver transplant
- Whole vs partial, split, living donor
- Donor and recipient positive for EBV/CMV
- Type of biliary reconstruction: duct-to duct vs Roux-y
Type of abdominal wall closure: (mesh?)
Vascular complications: hepatic artery or portal vein thrombosis - biliary complications: stricture/leak
- induction immunosuppression.
Immunosuppression after liver transplant
- Calcineurin inhibitors: Tacrolimus, Cyclosporine
- Prednisone/Solumedrol
- Anti-proliferative drugs: Mycophenolate, Azathioprine, Sirolimus.
- Antibodies: anti T-cell (induction, treatment of rejection)
- about 25% of kids are on double therapy and 115 are on triple therapy at 5 years.
Calcineurin inhibitors MOA
block T-cell signal transduciton/activation
mTORs (Sirolimus/Rapamune) MOA
- Suppress T cell proliferation
Antiproliferative drugs (mycophenolate) MOA
- Inhibit purine synthesis
Corticosteroids MOA
- multiple effects on inflammation
Anti T cell antibodies
OKT3 (anti-CD3_
thyroglobulin (anti-thymocyte)
Other antibodies MOA
- Basiliximab (anti IL-2_
- Daclizumab (anti IL-2)
Tacrolimus Toxicities
- Diabetes, HTN, Kidney injury, Neurotoxicity
Cyclosporine toxicities
Diabetes, HTN, Kidney, High lipids, Hirsutism, Gingival Hyperplasia
Siroliumus Toxicities
- High lipids, anemia, B.O. Proteinuria
Mycophenolate toxicities
GI symptoms, Bone marrow suppression
Prednisone Toxicities
Diabetes, HTN
Antibodies toxicities
Bone marrow suppression, PTLD, infusion reactions
Drug interactions
If you give transplant patient erythromycin, they will develop toxic level of prograf/cyclosporine and develop kidney failure.
- Drugs that block FK/Cyclo/mTOR metabolism and increase levels: Macrolides (EES, clarithromycin), Azoles (Fluconazole), Others: protease inhibitors, grapefruit juice, Regland.
- Drugs that INCREASE FK/Cyclor/mTOR metabolism and decrease levels: St. John’s wort, Rifamin, Anticonvulsants.
NSAIDS intensify the kidney injury from Calcineurin inhibitors.
Outcomes/Prognosis of liver transplant
- at 5 years survival is >80%.
- best survival is live donor. Least survival: decreased donor split.
Prognosis is worse for patients with re-transplant, technical varian graft. Etiology: BA is best, malignancy is worst.
Age/size: >1 year is better, less than 6kg is worse.
Nutritional state/sarcopenia/ascites: worse prognosis.
Hyponatremia is worse, requiring ventilator or dialysis is worse
Complications of Liver transplant
- primary graft non-function
- vascular complications: hepatic artery thrombosis (can lead to liver failure or biliary strictures), portal vein thrombosis (can lead to portal HTN), hepatic vein outflow obstruction (can lead to graft dysfunction).
- biliary strictures/leaks: can present with elevated liver enzymes, elevated bili
- rejection
- malignancy
- infection
Rejection
Acute rejection: 7 days to years after transplant
Sxs: rare
Lab: elevated AST/ALT, GGT, alk phos (later elevation: bili)
DDX: biliary issues or infx
- Bx findings: lymphocytic portal infiltrates, bile duct damage, endothelialitis.
- Management: increased immunosuppression: steroids, anti-t-cell antibody, then optimize maintenance.
Acute rejection: bile duct injury and endothelialitis
Chronic Rejection
- Timing: late, after frequent/severe rejection
- jaundice and pruritic
- elevated GGT, alk phos and bili more so than ALT/AST.
- Ddx: biliary obstruction
-Bx findings: bile duct loss: foam cell obliterative arteriopathy - Tx: modify immunosuppression
Chronic rejection biopsy findings: Foam cell obliterative arteriopathy and bile duct loss
Infections
-early infx (first 30 days): surgical, wound, catheters
- intermediate infx: 1-6 months: CMV, can be asymptomatic, occurs once prophylaxis is stopped with high immunosuppression
Pneumocystitis (prophylaxis for 6 months). Cholangitis if biliary issues
- later infections (after 6 months): usually community acquired infections which are handled well.
PTLD: lymphoma like condition of transplant patients in general, usually 90% of time associated with EBV infection
Sxs: fever, malaise, pharyngitis, adenopathy, GI symptoms, pneumonitis
- lymphocytosis, leukopenia, thrombocytopenia, someitmes hepatitis
Dx: quantitative EBV PCR, imaging, bx
PTLD can affect liver, lymph nodes, gut and brain.
Treatment of PTLD: reduce immunosuppression, antivirals are controversial, Anti CD-20 antibody (RItuximab).
Chemotherapy when needed:
PTLD: way too many lymphocytes
Long term complications of liver transplant
- Renal dysfunction
- Dyslipidemia
-Cardiovascular
Psych, hearing loss
