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![Page 1: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/1.jpg)
![Page 2: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/2.jpg)
Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease
CME Tbilisi 24/10/2015
Evi Nagler
![Page 3: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/3.jpg)
Programme
HCV-related kidney disease
Hepatitis C
![Page 4: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/4.jpg)
Programme – not covering
Hepatitis C Chronic kidney disease
![Page 5: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/5.jpg)
Programme – not covering
Hepatitis C Chronic kidney disease
![Page 6: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/6.jpg)
Programme – not covering
Chronic kidney disease
Hepatitis C
![Page 7: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/7.jpg)
Hepatitis C virus
envelope
nucleocapsid
Single stranded RNA
![Page 8: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/8.jpg)
Heterogeneous
Gravitz. Nature 2011; 474: S1-S4
At least 6 different genotypes many many subtypes and strains
Differential response to treatmentHinders development of vaccines
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Transmission
Transfusions IV drug use Re-use
![Page 10: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/10.jpg)
Natural course – acute hepatitis c
![Page 11: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/11.jpg)
Natural course – chronic hepatitis c – 3% population
![Page 12: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/12.jpg)
Natural course – liver cirrhosis
![Page 13: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/13.jpg)
Natural course – liver failure or cancer
![Page 14: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/14.jpg)
Programme
HCV-related kidney disease
Hepatitis C
![Page 15: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/15.jpg)
1. Mixed cryoglobulinaemia syndrome2. Polyarteritis nodosa3. Membranous nephropathy
3 diseases affect kidney
![Page 16: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/16.jpg)
1. Mixed cryoglobulinaemia syndrome
Immune complex small-vessel vasculitis
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1. Mixed cryoglobulinaemia syndrome
Pathophysiology
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1. Mixed cryoglobulinaemia syndrome
• Pupura• Weakness• Arthralgia
Symptoms
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1. Mixed cryoglobulinaemia syndrome
Normal glomerulus Membranoproliferative GN
Thin capillary walls1-2 cells per capillary tuft
Thick capillary walls with Hypercellularity
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1. Mixed cryoglobulinaemia syndrome2. Polyarteritis nodosa3. Membranous nephropathy
3 diseases affect kidney
![Page 21: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/21.jpg)
2. Polyarteritis nodosa
Medium-vessel vasculitis
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2. Polyarteritis nodosa
?Pathophysiology
![Page 23: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/23.jpg)
2. Polyarteritis nodosa
Pathophysiology
Fibrinoid necrosis of vessel wall
White blood cells
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2. Polyarteritis nodosa
• Pupura/ulcers• Livedo• Weakness• Arthralgia• Fever• Abdominal pain
Symptoms
![Page 25: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/25.jpg)
1. Mixed cryoglobulinaemia syndrome2. Polyarteritis nodosa3. Membranous nephropathy
3 diseases affect kidney
![Page 26: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/26.jpg)
3. Membranous nephropathy
Pathophysiology
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3. Membranous nephropathy
Normal glomerulus Membranous nephropathy
Thin capillary walls Thick capillary walls
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3. Membranous nephropathy
• oedema
Symptoms
![Page 29: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/29.jpg)
1. Mixed cryoglobulinaemia syndrome2. Polyarteritis nodosa3. Membranous nephropathy
3 diseases affect kidney
![Page 30: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/30.jpg)
1. Antiviral strategies2. Immunosuppresive strategies
2 treatment strategies
![Page 31: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/31.jpg)
1. Antiviral strategies
1. Peg-Interferon + ribavirin2. Peg-Interferon + ribavirin + direct-acting antivirals 3. Direct-acting antivirals +/- ribavirin
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1. Antiviral strategies - mechanisms
1. Interferon
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1. Antiviral strategies - mechanisms
1. Peg-Interferon
Interferon
Poly-ethyleen glycol
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1. Antiviral strategies - mechanism
2. Ribavirin
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1. Antiviral strategies - mechanism
2. Direct-acting antivirals
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1. Antiviral strategies – viral clearance
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1. Antiviral strategies – Side effects Interferon
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1. Antiviral strategies – Hypothesis
Chronic Hepatitis C
Liver failureDeath
Chronic Hepatitis C
Liver failureDeath
Viral clearance
Liver failureDeath
Viral clearance
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1. Antiviral strategies – effectiveness in MCS
1. Peg-Interferon + Ribavirin
N=9
1 year
No virus=7Clinical response=7
2.5 year
Stop treatment
Coucoub et al. Arthr&Reum 2005; 52: 911-915
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1. Antiviral strategies – effectiveness in MCS
2. Peg-Interferon + Ribavirin + direct antivirals
?
![Page 41: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/41.jpg)
1. Antiviral strategies – safety in CKD
1. Peg-Interferon + Ribavirin
HemolyticAnaemia
renal clearance= reduce dose
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1. Antiviral strategies – safety in CKD
2. Direct antivirals
?
![Page 43: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/43.jpg)
1. Antiviral strategies2. Immunosuppressive strategies
2 treatment strategies
![Page 44: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/44.jpg)
2. Immunosuppressive strategies
1. Rituximab2. Corticosteroids3. Plasmapheresis4. Cyclophosphamide
![Page 45: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/45.jpg)
2. Immunosuppressive strategies - MCS
1. Rituximab2. Corticosteroids3. Plasmapheresis4. Cyclophosphamide
![Page 46: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/46.jpg)
2. Immunosuppressive strategies - MCS
1. Rituximab
rituximab
![Page 47: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/47.jpg)
2. Immunosuppressive strategies - MCS
1. Rituximab
59
Rituximab Best available alternative
De Vita et al. Arthr&Rheum 2012; 64: 843-853
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2. Immunosuppressive strategies - MCS
1. Rituximab2. Corticosteroids3. Plasmapheresis4. Cyclophosphamide
![Page 49: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/49.jpg)
2. Immunosuppressive strategies - MCS
2. Corticosteroids
Damacco et al. Blood 1994; 64: 843-853
Probability of complete response
65
Infα +16 mg methylpred 16 mg methylpred
No treatmentInfα
![Page 50: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/50.jpg)
2. Immunosuppressive strategies - MCS
1. Rituximab2. Corticosteroids3. Plasmapheresis4. Cyclophosphamide
![Page 51: Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease CME Tbilisi 24/10/2015 Evi Nagler.](https://reader036.fdocuments.in/reader036/viewer/2022081520/5697bf9e1a28abf838c9483a/html5/thumbnails/51.jpg)
Conclusions
• 3 diseases• 2 treatment strategies
antiviralimmunosuppressive
• Very few data, mainly in mixed cryoglobulinaemia syndrome
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