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.
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Hepatitis c with renal disease
1. Hepatitis C and renal diseaseHepatitis C and renal disease
Dr. Mohamed AbbassDr. Mohamed Abbass
NephrologistNephrologist
PGDD, CARDIFF, UKPGDD, CARDIFF, UK
2. Hepatitis C virus infection is associated with manyHepatitis C virus infection is associated with many
renal diseases.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, DM,•Has extrahepatic manifestation like arthritis, DM,
cryglobulinemia and glomerulonephritiscryglobulinemia and glomerulonephritis
5.
6. 11..The most common types isThe most common types is MPGN with cryoglobulinemia
2. Others are:2. Others are:
MPGN without cryoglobulinemiaMPGN without cryoglobulinemia
Membranous nephropathy (MN) Membranous nephropathy (MN)
Focal segmental glomerulosclerosisFocal segmental glomerulosclerosis
IgA nephropathy IgA nephropathy
Fibrillary glomerulopathyFibrillary glomerulopathy
Immunotactoid glomerulopathy Immunotactoid glomerulopathy
Thrombotic microangiopathyThrombotic microangiopathy
Amyloid Amyloid
VasculitisVasculitis
Interstitial nephritis secondary to virus Interstitial nephritis secondary to virus
HCV-associated PANHCV-associated PAN
7.
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 complexesFormation of immune complexes
2- Formation of mixed cryoglobulinemia2- Formation of mixed cryoglobulinemia
3-3- Direct injury→ HCV has the ability to bind and penetrate theDirect injury→ HCV has the ability to bind and penetrate the
parenchyma cells by the CD 81 and SR-B1 receptors → HCVparenchyma 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 the6- HCV causes hyperisulinemia and insulin resistance → increases the
IGF-1 (insulin like growth factor -1) and TGF-B (transforming growthIGF-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 to chronicThe HCV escape from immune system this leading to chronic
viremiaviremia →→immune complex will be formedimmune complex will be formed →→ will deposit inwill deposit in
glomeruliglomeruli→→ attract the platelets, neutrophils, andattract the platelets, neutrophils, and
macrophagesmacrophages →→ complement activation with chemokinecomplement activation with chemokine
generationgeneration
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 cellsStimulation 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 proliferation andThe chronic infection of HCV leads to excessive proliferation and
stimulation of B cells and formation of type II cryoglobulin→ type IIstimulation of B cells and formation of type II cryoglobulin→ type II
mixed cryoglobulinemiamixed cryoglobulinemia
1-1-Deposition of cryoglobulin in the glomerular capillary and mesangiumDeposition of cryoglobulin in the glomerular capillary and mesangium
2-2-Causes vasculitis and fibrinoid necrosisCauses vasculitis and fibrinoid necrosis
3-3-Cryoglobulin can cause nephrotoxicity by attack the cellular fibronectinCryoglobulin can cause nephrotoxicity by attack the cellular fibronectin
in the mesangial matrixin the mesangial matrix
4-4- Cryoglobulins cause vasculitis by deposition in the small-sizedCryoglobulins cause vasculitis by deposition in the small-sized arteriesarteries
→ fix complement →cause local inflammation and injury→ fix complement →cause local inflammation and injury
13. Clinical pictures of renalClinical pictures of renal
diseases due to HCVdiseases due to HCV
14. Patients with chronic hepatitis c may hasPatients 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 cryoglobulinemia)5-Triad of purpura , asthenia , arthralgia ( GN with cryoglobulinemia)
6-The purpura is palpable , which consists of leukocytoclastic vasculitis,6-The purpura is palpable , which consists of leukocytoclastic vasculitis,
this lesions mostly found in the lower limb or can found anywhere, thisthis lesions mostly found in the lower limb or can found anywhere, this
represent small vessel vasculitisrepresent small vessel 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 according to types of8-There are different presentation of renal disease according to types of
glomerulonephritisglomerulonephritis
16. Laboratory tests +Renal biopsyLaboratory tests +Renal biopsy
1-Anti-HVC antibody and HCV RNA in serum1-Anti-HVC antibody and HCV RNA in serum
2-Elevated serum transaminase in > 70% of patients2-Elevated serum transaminase in > 70% of patients
3-Cryoglobulin can be detected in > 50% of patients3-Cryoglobulin can be detected in > 50% of patients
4-Rheumatoid factors may be +ve4-Rheumatoid factors may be +ve
18. 11--Renal biopsy show changes according to type ofRenal biopsy show changes according to type of
glomerulonephritisglomerulonephritis
2-Membranoproliferative glomerulonephritis type I is2-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 (double3-Splitting of capillary basement membranes (double
contouring- tram tracks )contouring- tram tracks )
4-Intracapillary thrombosis due to cryoglobulin deposition4-Intracapillary thrombosis due to cryoglobulin deposition
5-Vasculitis and fibrinoid necrosis5-Vasculitis and fibrinoid necrosis..
21. EM:EM:
1-Large subendothelial deposits (different from1-Large subendothelial deposits (different from
idiopathic MPGN where the subendothelial depositsidiopathic MPGN where the subendothelial deposits
are much smaller)are much smaller)
2-These subendothelial deposits are so large they2-These subendothelial deposits are so large they
may protrude into the capillary lumen, causingmay protrude into the capillary lumen, causing
thrombosisthrombosis..
23. The policy of treatment depend on the renal function
1-In non- nephrotic , normal renal function1-In non- nephrotic , normal renal function →→ interferon alfainterferon alfa
2-In nephrotic syndrome , renal impairment or with cryoglobulinemia →2-In nephrotic syndrome , renal impairment or with cryoglobulinemia →
pegylated interferon alfapegylated interferon alfa (1 ug/kg week )+(1 ug/kg week )+ ribavirinribavirin(15 mg/kg/day) for 12(15 mg/kg/day) for 12
months then short course of low-dose corticosteroidsmonths then short course of low-dose corticosteroids
3-In Rapidly progressive renal failure:3-In Rapidly progressive renal failure: methylprednisolonemethylprednisolone (1 g/ day) for(1 g/ day) for
3 days, followed by3 days, followed by oral prednisoneoral prednisone (60 mg/day) with slow taper over 2-3(60 mg/day) with slow taper over 2-3
monthsmonths
4-4-Plasma exchangePlasma exchange to remove cryoglobulins (3/week for 2 – 3 weeks)to remove cryoglobulins (3/week for 2 – 3 weeks)
24. 5-5-RituximabRituximab to stop further B cell productionto stop further B cell production
(375mg/m 2 weekly for 4 weeks) or in resistance(375mg/m 2 weekly for 4 weeks) or in resistance
casescases
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-Use7-Use erythropoietinerythropoietin to keep Hb>110 g/L (ribavirinto keep Hb>110 g/L (ribavirin
causes red cell fragility)causes red cell fragility)
8-8-ACE-1/ARBACE-1/ARB to reduce proteinuria ( uPCR<50to reduce proteinuria ( uPCR<50
mg/mmol) also to control blood pressure ( aim <mg/mmol) also to control blood pressure ( aim <
130/80mmHg130/80mmHg