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| معلومات للمرضى | فيروس |
Research |
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Pathology of
Liver Transplantation
Historical Overview.- v, 1967Starzl et al., carried out the first successful human liver transplant - vResults were poor: Fewer than 30% survived more than 1year. Subsequent improvements in preservation of donor organs, surgical techniques and immunosuppressive therapy, led to 80% survival more than 1year vNational Liver Institute: real solid steps began on 2001 - Indications for LT in Adults.- v Chronic liver diseases (70-80%): Cirrhotic liver, Autoimmune liver diseases, Metabolic liver diseases Acute hepatic-failure (5-15%): Acute/subacute nonA nonB nonC hepatitis, fulminant hepatitis A, B or E, paracetamol toxicity (other drug), Wilson’s disease (acute presentation) Malignancy : HCC, cholangiocarcinoma Liver metabolic defect without liver disease: primary hyperoxaluria, familial amyloid polyneuropathy
Indications for LT in Children.- Chronic liver diseases (75-80%) EHBA (failure of portoenterostomy), A1ATD, cystic fibrosis, Alagille syndrome, hereditary tyrosinaemia, AIH, sclerosing cholangitis, cryptogenic cirrhosis, Wilson’s ds., PFIHC Acute hepatic-failure (9-17%): Acute/subacute nonA nonB nonC hepatitis, fulminant hepatitis A, paracetamol toxicity (other drug), Wilson’s disease (acute presentation) Malignancy (<4%): hepatoblastoma, others Pathological Assessment in LT.- Examination of native liver removed at operation - Confirm clinic pathological diagnosis Provide a better understanding of the way which liver diseases are distributed within the liver Time zero biopsy: from donor liver immediately after reperfusion - pre-existing disease in the donor liver identify changes related to organ preservation and reperfusion Pathological Assessment in LT.- First month - Preservation/reperfusion injury Ischaemia Rejection 1-12months - Biliary complications Opportunistic infection Recuurrent disease Types of Rejection.- Hyperacute (humoral) Rejection - Acute (Cellular) Rejection - Chronic (ductopenic) Rejection- Hyperacute Rejection.- Definition: graft dysfunction and failure occurring immediately after reperfusion in a recipient with performed anti-donor antibodies Incidence: 33% with incompatible ABO, Occasionally with compatible ABO Clinical features: initial period of stable graft function (up to 2 weeks), followed by rise in serum aminotransferases, prolonged prothrombin time, signs of acute kiver failure, indirect signs of humoral mediated injury Immunosuppressive therapy is ineffective Urgent re-transplantation is indicated Hyperacute Rejection.- Histological features Deposition of fibrin, platelets, neutrophils & RBCs in small vessels and sinusoids Endothelial injury: neutrophilic exudation, congestion, coagulative hepatocyte necrosis Diffuse massive haemorrhagic necrosis Lack of lymphocytic infiltrate Deposition of immunoglobulins, complement and fibrinogen in vascular & sinusoidal endothelium Hyperacute rejection.- Massive haemorrhagic necrosis DD of Hyperacute Rejection.- Preexisting donor lesion (severe fatty change Preservation reperfusion injury Non humoral factors which have been postulated in graft failure: gram –ve sepsis, opportunistic viral infection ( herpes simplex, herpes zoster, adenovirus, enterovirus Acute Rejection.- Definition: Immune-mediated damage to the liver allograft characterized by cellular infiltrate, damage to bile ducts & vascular structures Incidence: Clinically: 20-50%; Histologically: 80% end of first week following transplantation Clinical features: pyrexia, graft enlargement, tenderness, reduced bile flow
Histological Features of AR .- Diagnostic triad: Portal inflammation: T cell, activated blast cell, macrophage, neutrophil, eosinophil Bile duct damage Venular endothelial inflammation: portal & hepatic Grading of AR: Grade I (mild Grade II (moderate Grade III (severe Chronic Rejection.- vDefinition: immune-mediated damage to the liver allograft which is characterized histologically by 2 main features loss of small bile ducts and an obliterative vasculopathy affecting large and medium sized arteries Incidence 2-20% Risk factors: donor/recipient factors; transplantation for AIH liver, sex mismatching of donor to recipient post-transplantation factors; related to acute rejection, including the number of episodes, severity, late presentation, other infections, hepatitis B,C, interferon therapy for viral hepatitis Banff scheme for staging chronic rejection .- Early CR vs Late CR Small bile ducts: degenerative changes, 50% loss Terminal hepatic venules: intimal/medial inflammation, perivenular necrosis & inflammation Portal tract hepatic arteriole; occasional loss 25% Other: transition hepatitis with spotty necrosis Large perihilar hepatic artery branches: intimal infiltrate, focal foam cell deposition Large perihilar bile ducts: inflammatory damage and focal foam cell deposition
DD of Chronic Rejection.- Recurrent viral hepatitis Recurrent biliary disease Ischaemic cholangiopathy DD of perivenular lesions: Vascular problems (hepatic veno-occlusive lesions Viral hepatitis, AIH, Drug toxicity Targets for immune damage in Acute and chronic rejection Bile ducts Vascular endothelial cells Hepatocytes Kupffer cells
Immunopathogenesis of AR & CR .-
Afferent arm: presentation of graft alloantigens and the recognition of these antigens by recipient T cells Phase of T cell activation: cytokine release, autocrine and paracrine effect on target cells Efferent arm: recruitment and activation of effector cells which mediate damage to target structures within the allograft Complications of Liver Transplantation .- Infection: viral: CMV, EBV, opportunistic viruses, Hepatitis B, C virus Bacterial: gram negative sepsis fungal: aspergillus and candida Vascular problems Biliary complications Disease recurrence
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