curs 3 - imunologia transplantului -ficat+inima
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Liver transplantation andLiver transplantation and heart transplantation heart transplantation
Prof. Ileana ConstantinescuProf. Ileana Constantinescu
The single most effective therapy for end –stage liver failure (ESLF) is liver transplantation (LT).
• European Liver Transplant Registry:
70.000 LT have been performed in 137 centres around Europe.
UK: currently 680 liver transplants are performed yearly. More than 6000 patients have been transplanted
RO: about 30-50-60 LT/year
Unfortunately the supply cannot meet demand
Indications for LT - adultsCommon:1.Alcoholic liver disease (ALD)2.Cryptogenic cirrhosis3.Primary biliary cirrhosis4.Primary sclerosing cholangitis (PSC)5.Hepatitis (B, C, non-A, non-B)6.Hepatocellular cancer7.Autoimmune hepatitis
Indications for LT - adultsRare:1.Haemochromathosis2.Wilson’s disease3.Α1-antitrypsin deficiency4.Budd-Chiari syndrome5.Polycystic disease6.Hyperoxaluria, familial hypercholesterolaemia7.Porphyrias, amyloidosis, neuroendocrine
tumours (e.g. carcinoid)
Indications for LT in children• Biliary atresia• Familial cholestasis syndromes• Metabolic disorders:
Cystic fibrosisΑ1-antitrypsin deficiencyCrigler-Najjar type 1Wilson’s disease
• Unresectable tumours (e.g. hepatoblastomas)• Acute liver failure – viral, drugs (e.g. paracetamol
toxicity), autoimmune
Contraindications to liver transplantation
Absolute:1.Infection2.Malignancy outside the hepatobiliary system3.Secondary hepatic malignancy4.Active drug or alcohol abuse5.Advanced cardiopulmonary disease
Contraindications to liver transplantation
Relative:1.Age over 65 years2.Portal vein thrombosis3.Renal failure not associated with liver disease4.Intrahepatic sepsis5.HIV
Emmergencies for LT• Paracetamol poisoning• Diuretic-resistant ascites• Hepatopulmonary syndromes• Chronic hepatic encephalopathy• Persistent and intractable pruritus• Familial amyloidosis• Primary hyperlipidaemias• Polycystic liver disease
Work-up for liver transplantation• Assessment for conventional deceased donor
1.Blood group2.Conventional liver screen/liver biopsy for steatosis3.Viral screening4.HLA typing: HLA-A, B, DRB15.Tumor markers: AFP, CA 19-9, CEA, CA 125, CA 15-3, β2-microglobulin, total and free PSA
Work-up for liver transplantation• Assessment for liver donation
1. Blood group2. Conventional liver screen/liver biopsy for steatosis3. Viral screening4. HLA typing: HLA-A, B, DRB15. Tumor markers: AFP, CA 19-9, CEA, CA 125, CA 15-3,
β2-microglobulin, total and free PSA6. To exclude occult thromboembolic disorders:
abnormalities for PT, protein C, protein S, antithrombine III, factor V Leiden, factor VIII, cardiolipin , antiphospholipin
Immunology of liver transplantation in the recipient
• AB0 compatibility• Viral screening• Child Pugh score: A, B, C• MELD score (Model for End-stage Liver Disease)3.8 x loge (bilirubin mg/dL) + 11.2 x loge (INR) + 9.6
loge (creatinine mg/dL) + 6,4 (aetiology: 0 if cholestatic or alcoholic, 1 otherwise)
Immunology of liver transplantation in the recipient
• Histocompatibility testing plays little role in selecting an individual recipient for LT for a particular donor
• Class I HLA matching may significantly improve patient graft survival.
• In the liver tissue HLA class I antigens are to be found only on the biliar epithelium, but not on the hepatocytes
• HLA class II antigens are present in Kupffer cells and endotelial cells.
• Cytotoxic antibodies• Crossmatch – a positive crossmatch is associated with a
higher likelihood of early rejection episodes.
Heart transplantation
• Indications – adults1.Coronary-related heart failure2.Cardiomyopathies : valvular, mixt diagnoses,
adult congenital, retransplantation
• Indications – paediatrics (<16 years)1.Cardiomyopathy2.Congenital heart disease
Recipient assesment protocol for heart transplantation
• Full blood count, plateletes, coagulation screening• Blood group• Uree, electrolytes, liver function, thyroid function• Microbiology• Viral screening• Fasting glucose and lipids• ECG• Chest X Ray• Estimation of peak O2 consumption (VO2max)• Carotid/peripheral artery Doppler
Recipient assessment protocol for heart transplantation
• AB0 compatibility• Immunological matching
Anti-HLA antibodies ≈ 10% > 25% → rejection
• HLA typing for A, B, DRB1• Crossmatch• Chronic transplant dysfunction in transplanted
hearts remains the most common cause of graft loss after the first year postTx.