Hepatitis C related kidney disease

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Presentation transcript:

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

Programme Hepatitis C HCV-related kidney disease

Programme – not covering Hepatitis C Chronic kidney disease

Programme – not covering Hepatitis C Chronic kidney disease

Programme – not covering Hepatitis C Chronic kidney disease

Hepatitis C virus envelope Single stranded RNA nucleocapsid

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

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 Hepatitis C HCV-related kidney disease

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

1. Mixed cryoglobulinaemia syndrome Immune complex small-vessel vasculitis

1. Mixed cryoglobulinaemia syndrome Pathophysiology

1. Mixed cryoglobulinaemia syndrome Symptoms Pupura Weakness Arthralgia

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

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

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

2. Polyarteritis nodosa ? Pathophysiology

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

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

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

3. Membranous nephropathy Pathophysiology

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

3. Membranous nephropathy Symptoms oedema

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

2 treatment strategies 1. Antiviral strategies 2. Immunosuppresive strategies

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

1. Antiviral strategies - mechanisms 1. Interferon

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

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 failure Death Viral clearance Liver failure Death Chronic Hepatitis C Liver failure Death Viral clearance

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: 911-915

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

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

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

2 treatment strategies 1. Antiviral strategies 2. Immunosuppressive strategies

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

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

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: 843-853

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

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

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