Hepatitis c with renal disease

Hepatitis C virus infection is associated with many renal diseases. �Renal disease caused by :�•Virus itself �•Drugs used for treatment of hepatitis c �•Associated condition with hepatitis → advanced liver cell failure.

1. Hepatitis C and renal diseaseHepatitis C and renal disease
Dr. Mohamed Abbass Dr. Mohamed Abbass
Nephrologist Nephrologist
PGDD, CARDIFF, UKPGDD, CARDIFF, UK

2. Hepatitis C virus infection is associated with Hepatitis C virus infection is associated with
many renal diseases. many renal diseases.
Renal disease caused by :Renal disease caused by :
•Virus itself •Virus itself
•Drugs used for treatment of hepatitis c •Drugs used for treatment of hepatitis c
•Associated condition with hepatitis → •Associated condition with hepatitis →
advanced liver cell failure. advanced liver cell failure.

3. 1–The renal disease associated with
hepatitis c due to advanced liver cell
failure:
•Prerenal →(Hypovolemia , shock and
hepatorenal syndrome)
•ATN →(sepsis or shock)
2– Drugs used for treatment of hepatitis
c:
Interstitial nephritis secondary to
interferon

4. 3–Hepatitis c itself:3–Hepatitis c itself:
••Hepatitis c is RNA flavivirus(single strand) Hepatitis c is RNA flavivirus(single strand)
•Has extrahepatic manifestation like arthritis, •Has extrahepatic manifestation like arthritis,
DM, cryglobulinemia and glomerulonephritis DM, cryglobulinemia and glomerulonephritis

6. 11. . The most common types is The most common types is MPGN with
cryoglobulinemia
2. Others are: 2. Others are:
  MPGN without cryoglobulinemia MPGN without cryoglobulinemia
 Membranous nephropathy (MN)  Membranous nephropathy (MN)
  Focal segmental glomerulosclerosis Focal segmental glomerulosclerosis
 IgA nephropathy  IgA nephropathy
  Fibrillary glomerulopathy Fibrillary glomerulopathy
 Immunotactoid glomerulopathy  Immunotactoid glomerulopathy
  Thrombotic microangiopathy Thrombotic microangiopathy
 Amyloid  Amyloid
  VasculitisVasculitis
 Interstitial nephritis secondary to virus  Interstitial nephritis secondary to virus
  HCV-associated PANHCV-associated PAN

8. There are many methods of renal diseases in hepatitis c: There are many methods of renal diseases in hepatitis c:
1- 1- Formation of immune complexes Formation of immune complexes
2- Formation of mixed cryoglobulinemia 2- Formation of mixed cryoglobulinemia
3- 3- Direct injury→ HCV has the ability to bind and penetrate the Direct injury→ HCV has the ability to bind and penetrate the
parenchyma cells by the CD 81 and SR-B1 receptors → HCV parenchyma cells by the CD 81 and SR-B1 receptors → HCV
endocytosis! endocytosis!
4- Some time the HCV RNA causes podocytes injury! 4- Some time the HCV RNA causes podocytes injury!
5- HCV react with Toll –like receptors (TLR3)→ IL6, IL8! 5- HCV react with Toll –like receptors (TLR3)→ IL6, IL8!
6- HCV causes hyperisulinemia and insulin resistance → increases the 6- HCV causes hyperisulinemia and insulin resistance → increases the
IGF-1 (insulin like growth factor -1) and TGF-B (transforming growth IGF-1 (insulin like growth factor -1) and TGF-B (transforming growth
factors beta- 1)→ increase the oxidative stressfactors beta- 1)→ increase the oxidative stress! !

9. Mechanism of renal disease in HCV patientsMechanism of renal disease in HCV patients
↓↓

1-Immune
complexes
2-Mixed
cryogulobinemia
3-Direct
injury CD 81
4-Injury to
podocytes
5-Toll –like
receptors
6- Hyper
isulinemia and
IR

10. The immune complexes mechanism:The immune complexes mechanism:
The HCV escape from immune system this leading The HCV escape from immune system this leading
to chronic viremia to chronic viremia →→immune complex will be immune complex will be
formed formed →→ will deposit in glomeruli will deposit in glomeruli→→ attract the attract the
platelets, neutrophils, and macrophages platelets, neutrophils, and macrophages →→
complement activation with chemokine generation complement activation with chemokine generation
and leukocyte adhesion molecule expressionand leukocyte adhesion molecule expression

11. Capillary wall damage Cytokine and growth factorCapillary wall damage Cytokine and growth factor
Stimulation of mesangial cells Stimulation of mesangial cells
Proteinuria Mesangial cell proliferationProteinuria Mesangial cell proliferation

12. The formation of mixed cryoglobulinemia:The formation of mixed cryoglobulinemia:
The chronic infection of HCV leads to excessive The chronic infection of HCV leads to excessive
proliferation and stimulation of B cells and formation of type proliferation and stimulation of B cells and formation of type
II cryoglobulin→ type II mixed cryoglobulinemiaII cryoglobulin→ type II mixed cryoglobulinemia
1-1-Deposition of cryoglobulin in the glomerular capillary and Deposition of cryoglobulin in the glomerular capillary and
mesangiummesangium
2-2-Causes vasculitis and fibrinoid necrosisCauses vasculitis and fibrinoid necrosis
3-3-Cryoglobulin can cause nephrotoxicity by attack the Cryoglobulin can cause nephrotoxicity by attack the
cellular fibronectin in the mesangial matrixcellular fibronectin in the mesangial matrix
4- 4- Cryoglobulins cause vasculitis by deposition in the small-Cryoglobulins cause vasculitis by deposition in the small-
sized sized arteries → fix complement → cause local inflammation and injuryarteries → fix complement → cause local inflammation and injury

13. Clinical pictures of renal Clinical pictures of renal
diseases due to HCVdiseases due to HCV

14. Patients with chronic hepatitis c may has Patients with chronic hepatitis c may has
1-Proteinuria1-Proteinuria
2-Hematuria (microscopic)2-Hematuria (microscopic)
3-Deterioration of kidney functions3-Deterioration of kidney functions
4-HTN4-HTN
5-Triad of purpura , asthenia , arthralgia ( GN with 5-Triad of purpura , asthenia , arthralgia ( GN with
cryoglobulinemia)cryoglobulinemia)
6-The purpura is palpable , which consists of 6-The purpura is palpable , which consists of
leukocytoclastic vasculitis, this lesions mostly found in the leukocytoclastic vasculitis, this lesions mostly found in the
lower limb or can found anywhere, this represent small lower limb or can found anywhere, this represent small
vessel vasculitisvessel vasculitis
7-Low serum C4 ,C1q and CH50 but normal C37-Low serum C4 ,C1q and CH50 but normal C3
8-There are different presentation of renal disease 8-There are different presentation of renal disease
according to types of glomerulonephritisaccording to types of glomerulonephritis

15. Diagnosis

16. Laboratory tests +Renal biopsyLaboratory tests +Renal biopsy
1-Anti-HVC antibody and HCV RNA in 1-Anti-HVC antibody and HCV RNA in
serumserum
2-Elevated serum transaminase in > 70% of 2-Elevated serum transaminase in > 70% of
patientspatients
3-Cryoglobulin can be detected in > 50% of 3-Cryoglobulin can be detected in > 50% of
patientspatients
4-Rheumatoid factors may be +ve4-Rheumatoid factors may be +ve

17. PathologyPathology

18. 11--Renal biopsy show changes according to type of Renal biopsy show changes according to type of
glomerulonephritisglomerulonephritis
2-Membranoproliferative glomerulonephritis type I is 2-Membranoproliferative glomerulonephritis type I is
the most commonthe most common
3-Or any other types3-Or any other types

19. The Membranoproliferative glomerulonephritis type IThe Membranoproliferative glomerulonephritis type I
Light microscopy:Light microscopy:
1-Glomerular hypercellularity1-Glomerular hypercellularity
2-Increased matrix and mesangial proliferation2-Increased matrix and mesangial proliferation
3-Splitting of capillary basement membranes 3-Splitting of capillary basement membranes
(double contouring- tram tracks )(double contouring- tram tracks )
4-Intracapillary thrombosis due to cryoglobulin 4-Intracapillary thrombosis due to cryoglobulin
depositiondeposition
5-Vasculitis and fibrinoid necrosis5-Vasculitis and fibrinoid necrosis..

20. Immunofluorescence:Immunofluorescence:
Deposits of IgG, IgM, and C3 in granular Deposits of IgG, IgM, and C3 in granular
capillary wall distribution and the capillary wall distribution and the
mesangiummesangium

21. EM:EM:
1-Large subendothelial deposits (different 1-Large subendothelial deposits (different
from idiopathic MPGN where the from idiopathic MPGN where the
subendothelial deposits are much smaller)subendothelial deposits are much smaller)
2-These subendothelial deposits are so 2-These subendothelial deposits are so
large they may protrude into the capillary large they may protrude into the capillary
lumen, causing thrombosislumen, causing thrombosis..

22. TreatmentTreatment

23. The policy of treatment depend on the renal function
1-In non- nephrotic , normal renal function 1-In non- nephrotic , normal renal function →→ interferon alfainterferon alfa
2-In nephrotic syndrome , renal impairment or with 2-In nephrotic syndrome , renal impairment or with
cryoglobulinemia → cryoglobulinemia → pegylated interferon alfa pegylated interferon alfa (1 ug/kg week (1 ug/kg week
)+ )+ ribavirinribavirin(15 mg/kg/day) for 12 months then short course (15 mg/kg/day) for 12 months then short course
of low-dose corticosteroidsof low-dose corticosteroids
3-In Rapidly progressive renal failure: 3-In Rapidly progressive renal failure: methylprednisolonemethylprednisolone
(1 g/ day) for 3 days, followed by (1 g/ day) for 3 days, followed by oral prednisone oral prednisone (60 (60
mg/day) with slow taper over 2-3 monthsmg/day) with slow taper over 2-3 months
4-4-Plasma exchange Plasma exchange to remove cryoglobulins (3/week for 2 to remove cryoglobulins (3/week for 2
– 3 weeks)– 3 weeks)

24. 5-5-RituximabRituximab to stop further B cell production to stop further B cell production
(375mg/m 2 weekly for 4 weeks) or in (375mg/m 2 weekly for 4 weeks) or in
resistance casesresistance cases
6-6-CyclophosphamideCyclophosphamide for 2 – 4 months ) 1.5 for 2 – 4 months ) 1.5
– 2.0mg/kg daily orally)– 2.0mg/kg daily orally)
7-Use 7-Use erythropoietinerythropoietin to keep Hb>110 g/L to keep Hb>110 g/L
(ribavirin causes red cell fragility)(ribavirin causes red cell fragility)
8-8-ACE-1/ARBACE-1/ARB to reduce proteinuria to reduce proteinuria
( uPCR<50 mg/mmol) also to control blood ( uPCR<50 mg/mmol) also to control blood
pressure ( aim < 130/80mmHgpressure ( aim < 130/80mmHg

25. ThanksThanks
Dr. M. AbbassDr. M. Abbass