curs 3 - imunologia transplantului -ficat+inima

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.