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

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

14. 40 - 50% Salcedo Hepatology 2002

15. CV CV

16. Allo- vs Auto-immunity

19. 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?

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

21. 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

27. No treatment

30. “Darrell”

31. 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

32. 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

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

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

35. 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

36. Methods • Histological assessment

37. CL portal

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

39. 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

40. **

41. **

42. **

43. **

44. p=0.063

45. ns

46. *

47. *p=0.051

48. ns

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

50. 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