Liver Transplantation Pathology

Indications & Pre-Tx Eval - Liver Lifeline Launch

• Indications:
  • Acute Liver Failure (ALF): e.g., viral, drug-induced.
  • Chronic Liver Disease (CLD): Decompensated (ascites, varices, encephalopathy); MELD > 15.
  • Hepatocellular Carcinoma (HCC): Within Milan Criteria.
  • Metabolic: Wilson's, A1AT deficiency.
  • Cholestatic (end-stage): PSC, PBC.
• Pre-Tx Evaluation:
  • Severity: MELD/PELD score.
    • 📌 MELD: Bilirubin, Creatinine, INR.
  • HCC Staging: Milan Criteria (1 lesion ≤5cm; or ≤3 lesions, each ≤3cm; no major vascular/extrahepatic spread).
  • Contraindications: Active sepsis/extrahepatic malignancy, severe cardiorespiratory disease, active substance abuse.
  • Workup: Cardiac, pulmonary, renal, infectious, psychosocial.

⭐ MELD score (Bilirubin, Creatinine, INR) is key to predict 3-month mortality in cirrhosis & prioritize transplant.

Graft Types & Immunosuppression - Organ Offers & Immune Ops

• Graft Types:

  • Deceased Donor (DDLT): Whole, split, reduced-size.
  • Living Donor (LDLT): Right lobe (adults), left lateral (children).

• Immunosuppression:

  • Phases: Induction, Maintenance, Rejection treatment.
  • Key Drugs:

    Class	Drugs	MoA (Key)	Key SE (Path)
    CNIs	Tacrolimus, Cyclosporine	↓IL-2, ↓T-cell act.	Nephro/Neurotoxicity
    Antimetabolites	MMF, AZA	↓Lymph. prolif.	BM suppression, GI (MMF)
    mTOR inh.	Sirolimus, Everolimus	Block IL-2 signal, ↓T prolif	Delayed healing, Ulcers
    Steroids	Prednisone	Broad anti-inflam.	Hyperglycemia, ↑Infection

• Immune Ops: ABO compatibility essential. HLA matching beneficial. Crossmatch vital.

⭐ Tacrolimus, a common calcineurin inhibitor, is notorious for causing nephrotoxicity and neurotoxicity.

Rejection Pathology - Graft's Immune Gauntlet

⭐ Classic ACR triad (Banff V,B,E criteria): Venous endothelialitis (V), Bile duct injury (B), and Portal inflammation (E). At least two components usually needed for diagnosis.

Non-Rejection Complications - Post-Op Perils & Pathogens

• Vascular: Hepatic Artery Thrombosis (HAT) (early, common), Portal Vein Thrombosis (PVT).
• Biliary: Leaks (early), Strictures (anastomotic/ischemic, later).
• Infections: See table & timeline. Key examples:

  • CMV: "Owl's eye" inclusions.

  • EBV (PTLD): Atypical lymphoid infiltrates.

  • Aspergillus: Angioinvasion, septate hyphae.

• Disease Recurrence: HCV, HBV, HCC, PSC.
• Drug Toxicity: CNI nephrotoxicity.

⭐ HAT: most common vascular issue, risks graft loss. CMV: key opportunistic pathogen (1-6 mo).

Common Post-Transplant Infections

High-Yield Points - ⚡ Biggest Takeaways

• Hyperacute rejection: Minutes-hours, preformed anti-donor antibodies (ABO/HLA), irreversible graft damage.
• Acute cellular rejection (ACR): Most common (days-weeks), T-cell mediated; triad: endotheliitis, bile duct injury, eosinophils. Responds to immunosuppression.
• Chronic rejection: Months-years, ductopenic (vanishing bile duct syndrome) or vascular (obliterative arteriopathy), leads to graft loss.
• PTLD: EBV-driven B-cell proliferation; risk with high immunosuppression.
• Recurrence of primary disease (HCV, HCC) is a major concern.
• Opportunistic infections (CMV, fungal) are key complications.