2. Hepatitis C related kidney disease
Clinical Practice Guidelines – bridging the gap
CME Tbilisi 24/10/2015
Evi Nagler

3. Programme
Hepatitis C
HCV-related
kidney disease

4. Programme – not covering
Hepatitis C
Chronic kidney disease

5. Programme – not covering
Hepatitis C
Chronic kidney disease

6. Programme – not covering
Hepatitis C
Chronic kidney disease

7. Hepatitis C virus
envelope
Single stranded RNA
nucleocapsid

8. Heterogeneous At least 6 different genotypes
many many subtypes and strains
Differential response to treatment
Hinders development of vaccines
Gravitz. Nature 2011; 474: S1-S4

9. Transmission
Transfusions
IV drug use
Re-use

10. Natural course – acute hepatitis c

11. Natural course – chronic hepatitis c – 3% population

12. Natural course – liver cirrhosis

13. Natural course – liver failure or cancer

14. Programme
Hepatitis C
HCV-related
kidney disease

15. 3 diseases affect kidney
1. Mixed cryoglobulinaemia syndrome
2. Polyarteritis nodosa
3. Membranous nephropathy

16. 1. Mixed cryoglobulinaemia syndrome
Immune complex small-vessel vasculitis

17. 1. Mixed cryoglobulinaemia syndrome
Pathophysiology

18. 1. Mixed cryoglobulinaemia syndrome
Symptoms
Pupura
Weakness
Arthralgia

19. 1. Mixed cryoglobulinaemia syndrome
Normal glomerulus
Membranoproliferative GN
Thin capillary walls
1-2 cells per capillary tuft
Thick capillary walls with
Hypercellularity

20. 3 diseases affect kidney
1. Mixed cryoglobulinaemia syndrome
2. Polyarteritis nodosa
3. Membranous nephropathy

21. Medium-vessel vasculitis
2. Polyarteritis nodosa
Medium-vessel vasculitis

22. 2. Polyarteritis nodosa ?
Pathophysiology

23. Fibrinoid necrosis of vessel wall
2. Polyarteritis nodosa
Pathophysiology
Fibrinoid necrosis of vessel wall
White blood cells

24. 2. Polyarteritis nodosa Symptoms Pupura/ulcers Livedo Weakness
Arthralgia
Fever
Abdominal pain

25. 3 diseases affect kidney
1. Mixed cryoglobulinaemia syndrome
2. Polyarteritis nodosa
3. Membranous nephropathy

26. 3. Membranous nephropathy
Pathophysiology

27. 3. Membranous nephropathy
Normal glomerulus
Membranous nephropathy
Thin capillary walls
Thick capillary walls

28. 3. Membranous nephropathy
Symptoms
oedema

29. 3 diseases affect kidney
1. Mixed cryoglobulinaemia syndrome
2. Polyarteritis nodosa
3. Membranous nephropathy

30. 2 treatment strategies 1. Antiviral strategies
2. Immunosuppresive strategies

31. 1. Antiviral strategies 1. Peg-Interferon + ribavirin
2. Peg-Interferon + ribavirin + direct-acting antivirals
3. Direct-acting antivirals +/- ribavirin

32. 1. Antiviral strategies - mechanisms
1. Interferon

33. 1. Antiviral strategies - mechanisms
1. Peg-Interferon
Poly-ethyleen glycol
Interferon

34. 1. Antiviral strategies - mechanism
2. Ribavirin

35. 1. Antiviral strategies - mechanism
2. Direct-acting antivirals

36. 1. Antiviral strategies – viral clearance

37. 1. Antiviral strategies – Side effects Interferon

38. 1. Antiviral strategies – Hypothesis
Chronic Hepatitis C
Liver failure
Death
Viral clearance
Liver failure
Death
Chronic Hepatitis C
Liver failure
Death
Viral clearance

39. 1. Antiviral strategies – effectiveness in MCS
1. Peg-Interferon + Ribavirin
N=9
No virus=7
Clinical response=7
Stop treatment
1 year
2.5 year
Coucoub et al. Arthr&Reum 2005; 52:

40. 1. Antiviral strategies – effectiveness in MCS?
2. Peg-Interferon + Ribavirin + direct antivirals

41. 1. Antiviral strategies – safety in CKD
1. Peg-Interferon + Ribavirin
Hemolytic
Anaemia
renal clearance= reduce dose

42. 1. Antiviral strategies – safety in CKD?
2. Direct antivirals

43. 2 treatment strategies 1. Antiviral strategies
2. Immunosuppressive strategies

44. 2. Immunosuppressive strategies
1. Rituximab
2. Corticosteroids
3. Plasmapheresis
4. Cyclophosphamide

45. 2. Immunosuppressive strategies - MCS
1. Rituximab
2. Corticosteroids
3. Plasmapheresis
4. Cyclophosphamide

46. 2. Immunosuppressive strategies - MCS
1. Rituximab
rituximab

47. 2. Immunosuppressive strategies - MCS
1. Rituximab 59
Rituximab
Best available alternative
De Vita et al. Arthr&Rheum 2012; 64:

48. 2. Immunosuppressive strategies - MCS
1. Rituximab
2. Corticosteroids
3. Plasmapheresis
4. Cyclophosphamide

49. 2. Immunosuppressive strategies - MCS
2. Corticosteroids
Probability of complete response 65
Infα
No treatment
Infα +
16 mg methylpred
16 mg methylpred
Damacco et al. Blood 1994; 64:

50. 2. Immunosuppressive strategies - MCS
1. Rituximab
2. Corticosteroids
3. Plasmapheresis
4. Cyclophosphamide

51. Conclusions 3 diseases 2 treatment strategies antiviral
immunosuppressive
Very few data, mainly in mixed cryoglobulinaemia syndrome