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