SOLID ORGAN TRANSPLANTATION Prof. ÖZCAN GÖKÇE, MD Director of the Department of General Surgery Yeditepe University Hospital

Organ Source Cadaver Living donor Other species

HLA TYPING A-MATCH…FULL B-MATCH..ONE ANTIGEN DIFFERENT C-MATCH..TWO ANTIGENS DIFFERENT …..SO ON THE MORE CLOSER TO A-MATCH, THE MORE SUCCESSFULL KIDNEY TRANSPLANTATION

MAJOR HISTOCOMPATABILITY COMPLEX Class I - present on almost all nucleated cells (interesting exceptions include sperm and the cells of the trophoblast). Class II- present on Antigen Presenting Cells (macrophages, B cells, and dendritic cells). Class III- are not surface molecules, but instead are various proteins typically which have some immunological role (C2,C4,Tumor necrosis factor alpha and beta, various HSPs) Human HLA region [Highly Simplified version !] ---DP--DQ--DR------------C4--C2--etc---------------B--C--A---

Human MHC genes are highly polymorphic

IMMUNUSUPRESSION

IMMUNOSUPRESSIVE AGENTS T-CELL BLOCKERS GLUCOCORTICOIDS BIOLOGIC IMMUNOSUPPRESSION SITOTOXIC AGENTS

T-CELL BOCKERS CYCLOSPORINE-A TACROLIMUS SIROLIMUS CYCLOSPORINE AND TACROLIMUS ARE SELECTIVE CALCINEURIN INHIBITORS INHIBITION OF Th INDUCTION WHICH IS ACTIVATED BY IL-2

NFAT :Nuclear factor of activated T-cells FKBP: FK Binding protein

BIOLOGIC IMMUNOSUPPRESSION -Antilymphosite globulines(Polyclonal antibodies) (Atgam, timoglobulin) -Anti-CD3 monoclonal antibodies (OKT3, muromonab-CD3) all -mab, -imab and -umab suffixes -Anti-Tac, Anti-CD25 monoclonal antibodies (Basiliximab, daclizumab) Anti-CD25 Monoclonal Antibodies (Basiliximab and Daclizumab) Anti-CD52 Monoclonal Antibody Alemtuzumab (Campath-1h) Anti-CD20 (Rituximab) Monoclonal Antibodies to Adhesion Molecules anti–LFA-1 mAb (efalizumab) anti-CD4 mAb (priliximab)

New Agents 1. AEB: This is a new oral compound that effectively blocks early T-cell activation by selective inhibition of protein kinase C. Therefore, it has a different mechanism of action from that of calcineurin inhibitors, and early studies suggest it is not associated with the nephrotoxicity seen with calcineurin inhibitors. This agent is currently in phase II testing. 2. ISA247: This is a novel semisynthetic analogue of cyclosporine that is structurally similar to it except for a modification of a functional group. This agent has not been associated with the nephrotoxicity seen with cyclosporine and currently is in phase II testing. 3. Janus kinase-3 (JAK-3) inhibitors: JAKs are cytoplasmic tyrosine kinases that participate in the signaling of a broad range of cell surface receptors, particularly members of the cytokine receptor superfamily. JAK-3 is found primarily on hematopoietic cells and blocking this may provide a significant degree of selectivity in immunosuppression. It is currently in phase II trials.

16 DECEMBER 2006

Hepatocellular diseases Chronic liver disease Cholestatic Biliary atrezia Primary biliary cirrhosis Primary sclerozing cholangitis Familial cholestatic diseases Hepatocellular diseases Chronic viral hepatitis (hepatitis B, C, D) Drud related injury Alcoholic liver disease Idiopatic otoimmun liver disease Vascular diseases Budd-Chiari syndrome Veno-occlusive Hepatic Disease 

Unresectable hepatic malignancy Hepatocellular carcinoma Cholangiocarcinoma (Only selected patients) Epitelial hemangioendotelioma Isolated hepatic metastatic tumor Carcinoid tumor Pancreatic islet cell tumor

Metabolic Liver Disease Alpha-1 antitripsin deficiency Wilson’s disease Homozigot type II hiperlipoproteinemia Crigler-Najjar syndrome type I Eritropoetik protoporfiria Urea cycle disorders Glycogen storage diseases, type I and IV Tyrozinemia Hereditary hemochromatozis

Fulminant Liver Disease † Acute viral hepatitis †Drug related liver toxicity Halothane Gold Disulfiram(Antabuse) Acetaminophen Mushroom poisoning Other Metabolic liver disease Wilson’s disease Reye syndrome Organic aciduria

Methanol

Ethanol                                                     

Fomepizole Fomepizole is a competitive inhibitor of alcohol dehydrogenase

HEMODIALYSIS