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Post-transplant centrilobular hepatitis - rejection or autoimmune-like?

Post-transplant centrilobular hepatitis - rejection or autoimmune-like?. Andrew Clouston & Catherine Campbell Princess Alexandra Hospital, Australia University of Queensland, Australia. Outline. introduction pathology of CLH evolution possible pathogenesis. Centrilobular hepatitis.

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Post-transplant centrilobular hepatitis - rejection or autoimmune-like?

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  1. Post-transplant centrilobular hepatitis- rejection or autoimmune-like? Andrew Clouston & Catherine Campbell Princess Alexandra Hospital, Australia University of Queensland, Australia

  2. Outline • introduction • pathology of CLH • evolution • possible pathogenesis

  3. Centrilobular hepatitis • Acute rejection • Chronic rejection • Vascular • Autoimmune hepatitis • “Central venulitis”

  4. Centrilobular hepatitis • Acute rejection portal changes • Chronic rejection duct changes • Vascular imaging • Autoimmune hepatitis histo & autoAb • “Central venulitis”

  5. Allo- vs Auto-immunity

  6. Allo- vs Auto-immunity

  7. Allo- vs Auto-immunity

  8. De novo AIH post-OLT • elevated transaminases • typical histology • interface hepatitis ++ • plasma cells

  9. De novo AIH post-OLT • elevated transaminases • typical histology • interface hepatitis ++ • plasma cells • late – median 24 months • autoantibodies • response to pred / aza

  10. 40 - 50% Salcedo Hepatology 2002

  11. CV CV

  12. Allo- vs Auto-immunity

  13. Late centrilobular hepatitis • Tsamandas 1997 • AR -- prognosis good • Nakazawa 2000 • hepatitis -- prognosis OK • Hassoon 2004 • AR (50%) – prognosis poor • >> evolution into CR IS THIS A FORM OF AR or AIH?

  14. Case • 28 yr old man previous farm worker • 1994 cryptogenic cirrhosis • March 2003 OLTx ; uneventful post op course

  15. Case • 28 yr old man previous farm worker • 1994 cryptogenic cirrhosis • March 2003 OLTx ; uneventful post op course • June 2004 abnormal LFTs • Transaminitis, BR normal • Immunosuppression stable • prednisolone 5mg, tacrolimus • Biopsy ?AR

  16. No treatment

  17. “Darrell”

  18. 2005 Draft statement on late liver allograft dysfunction (Banff working group) • “Central venulitis” • “Centrilobular inflammation +/- hepatocyte necrosis/dropout” • Peri-venular inflammation • Peri-venular hepatocyte necrosis/dropout • Haemorrhage • Pigmented macrophages

  19. Ddx “central venulitis” (Banff) • Acute rejection as isolated central venulitis • Perivenular inflammation with hepatocyte dropout and haemorrhage • Grading system provided • “severe” – damage of >3 hepatocyte layers in some central veins • Variable outcome

  20. ? Form of autoimmune- like hepatitis Hypothesis – centrilobular hepatitis ? Pure centrilobular form of AR

  21. Aims • Characterise “centrilobular hepatitis” • Nature of the histological changes • Associated clinical features • Document the natural history • Investigate possible mechanism

  22. Methods • Prospectively accrued cases from 1999 • Prominent“centrilobular hepatitis” on biopsy • No portal tract changes of AR or CR • Clinical details • baseline, biopsy and follow up LFTs • baseline immunosuppression • change in treatment • auto-antibody status

  23. Methods • Histological assessment

  24. CL portal

  25. Results • Seen in 24 pts (182 transplants) – 13% • 30 - 2850 days post-OLT • Mean 1066 days (~ 3 years) i.e. “late allograft dysfunction”

  26. Rejection n= 1 n=24 Moderate interface hepatitis & typical autoAb Autoimmune-like hepatitis Centrilobular hepatitis n=13 Original disease Recurrent AIH n=5 Denovo AI-like hepatitis n=5

  27. **

  28. **

  29. **

  30. **

  31. p=0.063

  32. ns

  33. *

  34. *p=0.051

  35. ns

  36. Histology - summary • Milder portal infiltrates • Milder interface hepatitis • Fewer portal plasma cells • Minimal duct injury PT

  37. Histology - summary • Milder portal infiltrates • Milder interface hepatitis • Fewer portal plasma cells • Minimal duct injury • Milder degree of CL dropout • Similar inflammatory infiltrate (↓ PC) • Overall lobular scores similar • Minimal endothelialitis PT Lob

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