Liver Allograft Pathology
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Direct answer
Liver allograft biopsy interpretation is governed by timing before morphology: the first two weeks favour preservation-reperfusion injury, the first month peaks for T-cell-mediated acute rejection, and late biopsies raise recurrent disease (primary biliary cholangitis, PSC, autoimmune hepatitis, fatty liver disease), de novo autoimmune hepatitis, biliary obstruction, drug injury and post-transplant lymphoproliferative disorder. Acute rejection is the Banff triad — mixed portal inflammation with blasts and eosinophils, bile-duct epithelial damage (lymphocytosis, nuclear dyskariosis), and portal or hepatic venous endothelial inflammation — scored 0-3 in each compartment to a total rejection activity index (RAI) of 0-9, where 3-4 is mild, 5-6 moderate and 7-9 severe. Chronic rejection is defined by ductopenia affecting more than 50% of portal tracts and foam-cell arteriopathy, divided into early (potentially reversible) and late stages.
What you must remember
- Banff RAI scoring: portal inflammation, bile-duct damage and venous endothelial inflammation each scored 0-3; RAI 3-4 mild, 5-6 moderate, 7-9 severe — moderate and severe receive pulsed methylprednisolone.
- The triad needs at least two components (classically all three) in a mixed inflammatory backdrop including blast-like lymphocytes and eosinophils before acute rejection is signed out.
- Chronic rejection: loss of small intrahepatic bile ducts in over half of portal tracts, with or without foam-cell (lipid-laden macrophage) arteriopathy; early-stage ductopenia without duct loss progression can recover with increased immunosuppression, late-stage needs retransplant.
- Antibody-mediated rejection: sinusoidal and portal microvascular endothelial injury with C4d deposition, in the setting of donor-specific antibodies; in India, where living-donor and ABO-incompatible transplants are common, AMR is a practical, not theoretical, diagnosis.
- Preservation injury picture: portal oedema, neutrophilic cholangitis-limited injury, canalicular cholestasis in the first days, resolving spontaneously.
- Rejection versus recurrent HCV (historical): portal lymphoid aggregates with interface activity and sinusoidal lymphocytes favoured recurrent HCV; confluent necrosis steered toward rejection — a distinction DAAs have largely retired but exams still test.
- PTLD timeline: peaks in the first year, EBV-driven, ranges from plasmacytic hyperplasia to monomorphic diffuse large B-cell lymphoma, commoner in paediatric and heavily immunosuppressed recipients.
- Indian context: living-donor transplantation dominates Indian programmes; smaller-for-size grafts and ABO-incompatible transplantation add ischaemic cholangiopathy and AMR to the routine differential list.
Scoring a day-18 biopsy with rising transaminases
An adult living-donor recipient on tacrolimus develops rising transaminases and bilirubin at day 18; protocol biopsy is taken. The portal tracts are expanded by a mixed infiltrate — lymphocytes, occasional blasts, eosinophils and neutrophils. Bile ducts show lymphocytes breaching the basement membrane with flattened, dyskaryotic epithelial nuclei; the terminal hepatic venules display lymphocytes undercutting the endothelium. Cholestasis is mild, and the parenchyma shows scattered apoptotic hepatocytes.
Scoring proceeds compartment by compartment: portal inflammation 2, bile-duct damage 2, endothelial inflammation 2 — RAI 6, moderate acute cellular rejection. A sentence on what it is not completes the report: no viral inclusions, no ductopenia (every tract retains a duct), no portal oedema-only pattern to suggest preservation injury. Treatment follows the number: pulsed steroids with tacrolimus optimisation, and a follow-up biopsy if enzymes stall. Had the same biopsy shown only sparse portal lymphocytes with duct loss in 60% of tracts three months later, the diagnosis would swing to chronic rejection and the conversation to retransplant candidacy — the two ends of one immunological spectrum.
Where students slip
The recurring exam error is demanding all three Banff components before diagnosing rejection — the schema requires a mixed portal infiltrate plus at least two of the three features, and overstrictness delays steroid therapy. The second slip is confusing recurrent disease with rejection in late biopsies: recurrent PBC with its florid duct lesions, recurrent autoimmune hepatitis with plasma-cell-rich interface activity, and recurrent PSC with fibro-obliterative duct lesions each mimic or mask rejection, and the report should address each by name. Third, the de novo autoimmune hepatitis phenotype — plasma cells, interface activity, autoantibodies, elevated IgG in a transplanted patient without prior AIH — is frequently misfiled as rejection, with real treatment consequences (steroids rather than antirejection escalation alone).
Frequently asked questions
What three features constitute the Banff acute rejection triad?
Mixed portal inflammation, bile-duct epithelial damage and portal or hepatic venous endothelial inflammation — each scored 0-3 for a total RAI out of 9.
Which RAI totals define mild, moderate and severe rejection?
Three to four mild, five to six moderate, seven to nine severe, with moderate and severe grades treated with pulsed corticosteroids.
What defines chronic rejection in a liver allograft?
Ductopenia involving more than 50% of portal tracts with or without foam-cell arteriopathy, staged early (reversible) versus late (irreversible, retransplantation territory).
Why is antibody-mediated rejection practically relevant in Indian transplant units?
Living-donor and ABO-incompatible transplants are common in India, so donor-specific antibodies and C4d-positive microvascular injury form part of routine graft dysfunction workups.
When does post-transplant lymphoproliferative disorder typically appear?
Within the first year, usually EBV-driven, spanning plasmacytic hyperplasia to monomorphic B-cell lymphoma in the setting of intensive immunosuppression.