Clinical Practice Guidelines – bridging the gap Hepatitis C related kidney disease
CME Tbilisi 24/10/2015
Evi Nagler
Programme
HCV-related kidney disease
Hepatitis C
Programme – not covering
Hepatitis C Chronic kidney disease
Programme – not covering
Hepatitis C Chronic kidney disease
Programme – not covering
Chronic kidney disease
Hepatitis C
Hepatitis C virus
envelope
nucleocapsid
Single stranded RNA
Heterogeneous
Gravitz. Nature 2011; 474: S1-S4
At least 6 different genotypes many many subtypes and strains
Differential response to treatmentHinders development of vaccines
Transmission
Transfusions IV drug use Re-use
Natural course – acute hepatitis c
Natural course – chronic hepatitis c – 3% population
Natural course – liver cirrhosis
Natural course – liver failure or cancer
Programme
HCV-related kidney disease
Hepatitis C
1. Mixed cryoglobulinaemia syndrome2. Polyarteritis nodosa3. Membranous nephropathy
3 diseases affect kidney
1. Mixed cryoglobulinaemia syndrome
Immune complex small-vessel vasculitis
1. Mixed cryoglobulinaemia syndrome
Pathophysiology
1. Mixed cryoglobulinaemia syndrome
• Pupura• Weakness• Arthralgia
Symptoms
1. Mixed cryoglobulinaemia syndrome
Normal glomerulus Membranoproliferative GN
Thin capillary walls1-2 cells per capillary tuft
Thick capillary walls with Hypercellularity
1. Mixed cryoglobulinaemia syndrome2. Polyarteritis nodosa3. Membranous nephropathy
3 diseases affect kidney
2. Polyarteritis nodosa
Medium-vessel vasculitis
2. Polyarteritis nodosa
?Pathophysiology
2. Polyarteritis nodosa
Pathophysiology
Fibrinoid necrosis of vessel wall
White blood cells
2. Polyarteritis nodosa
• Pupura/ulcers• Livedo• Weakness• Arthralgia• Fever• Abdominal pain
Symptoms
1. Mixed cryoglobulinaemia syndrome2. Polyarteritis nodosa3. Membranous nephropathy
3 diseases affect kidney
3. Membranous nephropathy
Pathophysiology
3. Membranous nephropathy
Normal glomerulus Membranous nephropathy
Thin capillary walls Thick capillary walls
3. Membranous nephropathy
• oedema
Symptoms
1. Mixed cryoglobulinaemia syndrome2. Polyarteritis nodosa3. Membranous nephropathy
3 diseases affect kidney
1. Antiviral strategies2. Immunosuppresive strategies
2 treatment strategies
1. Antiviral strategies
1. Peg-Interferon + ribavirin2. Peg-Interferon + ribavirin + direct-acting antivirals 3. Direct-acting antivirals +/- ribavirin
1. Antiviral strategies - mechanisms
1. Interferon
1. Antiviral strategies - mechanisms
1. Peg-Interferon
Interferon
Poly-ethyleen glycol
1. Antiviral strategies - mechanism
2. Ribavirin
1. Antiviral strategies - mechanism
2. Direct-acting antivirals
1. Antiviral strategies – viral clearance
1. Antiviral strategies – Side effects Interferon
1. Antiviral strategies – Hypothesis
Chronic Hepatitis C
Liver failureDeath
Chronic Hepatitis C
Liver failureDeath
Viral clearance
Liver failureDeath
Viral clearance
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
1. Antiviral strategies – effectiveness in MCS
2. Peg-Interferon + Ribavirin + direct antivirals
?
1. Antiviral strategies – safety in CKD
1. Peg-Interferon + Ribavirin
HemolyticAnaemia
renal clearance= reduce dose
1. Antiviral strategies – safety in CKD
2. Direct antivirals
?
1. Antiviral strategies2. Immunosuppressive strategies
2 treatment strategies
2. Immunosuppressive strategies
1. Rituximab2. Corticosteroids3. Plasmapheresis4. Cyclophosphamide
2. Immunosuppressive strategies - MCS
1. Rituximab2. Corticosteroids3. Plasmapheresis4. Cyclophosphamide
2. Immunosuppressive strategies - MCS
1. Rituximab
rituximab
2. Immunosuppressive strategies - MCS
1. Rituximab
59
Rituximab Best available alternative
De Vita et al. Arthr&Rheum 2012; 64: 843-853
2. Immunosuppressive strategies - MCS
1. Rituximab2. Corticosteroids3. Plasmapheresis4. Cyclophosphamide
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
2. Immunosuppressive strategies - MCS
1. Rituximab2. Corticosteroids3. Plasmapheresis4. Cyclophosphamide
Conclusions
• 3 diseases• 2 treatment strategies
antiviralimmunosuppressive
• Very few data, mainly in mixed cryoglobulinaemia syndrome