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. A. The renal disease associated with hepatitis c due to advanced liver cell failure: • Prerenal (Hypovolemia , shock and hepatorenal syndrome ) • ATN ( sepsis or shock) B. Drugs used for treatment of hepatitis c: • Interstitial nephritis secondary to Interferon C. Hepatitis c itself o Hepatitis c is RNA flavivirus( single strand) o Has extrahepatic manifestation like arthritis, DM, cryglobulinemia and glomerulonephritis o Renal diseases associated with hepatitis C 1. The most common types is MPGN with cryoglobulinemia 2. Others are  MPGN without cryoglobulinemia  Membranous nephropathy (MN)  Focal segmental glomerulosclerosis  IgA nephropathy  Fibrillary glomerulopathy  Immunotactoid glomerulopathy  Thrombotic microangiopathy  Amyloid  Vasculitis  Interstitial nephritis secondary to virus  HCV-associated PAN

1. Hepatitis C and renal disease
Dr. Mohamed Abbass
Nephrologist
PGDD, CARDIFF, UK
Hepatitis C virus infection is associated with many renal diseases.
Renal disease caused by 
 Virus itself
 Drugsused for treatment of hepatitis c
 Associated condition with hepatitisadvanced liver cell failure.
A. The renal disease associated with hepatitis c due to advanced liver
cell failure:
 Prerenal (Hypovolemia , shock and hepatorenal syndrome )
 ATN ( sepsis or shock)
B. Drugs used for treatment of hepatitis c:
 Interstitial nephritis secondary to Interferon
C. Hepatitis c itself
o Hepatitis c is RNA flavivirus( single strand)
o Has extrahepatic manifestation like arthritis, DM, cryglobulinemia
and glomerulonephritis
o Renal diseases associated with hepatitis C
1. The most common types is MPGN with cryoglobulinemia
2. Others are
 MPGN without cryoglobulinemia
 Membranous nephropathy (MN)
 Focal segmental glomerulosclerosis
 IgA nephropathy
 Fibrillary glomerulopathy
 Immunotactoid glomerulopathy
 Thrombotic microangiopathy
 Amyloid
 Vasculitis
 Interstitial nephritis secondary to virus
 HCV-associated PAN
Pathogenesis:
There are many methods of renal diseases in hepatitis c patients:
1- Formation of immune complexes
2- Formation of mixed cryoglobulinemia

2. 3- Direct injury HCV has the ability to bind and penetrate the parenchyma
cells by the CD 81 and SR-B1 receptors  HCV endocytosis!
4- Some time the HCV RNA causes podocytes injury!
5- HCV react with Toll –like receptors (TLR3)  IL6, IL8!
6- HCV causes hyperisulinemia and insulin resistance increases the IGF-1
(insulin like growth factor -1) and TGF-B (transforming growth factors
beta- 1) increase the oxidative stress!
There are some suggested methods of renal disease in HCV patients
The immune complexes mechanism:
The HCV escape from immune system this leading to chronic viremia  immune
complex will be formed  will deposit in glomeruli attract the platelets,
neutrophils, and macrophages  complement activation with chemokine
generation and leukocyte adhesion molecule expression
Capillary wall damage Cytokine and growth factor
Stimulation of mesangial cells
Proteinuria Mesangial cell proliferation
The formation of mixed cryoglobulinemia:
The chronic infection of HCV leads to excessive proliferation and stimulation of B
cells and formation of type II cryoglobulin type II mixed cryoglobulinemia
 Deposition of cryoglobulin in the glomerular capillary and mesangium
 Causes vasculitis and fibrinoid necrosis
Mechanism of renal disease in HCV patients
Immune
complexes
Mixed
cryoglobulinemia
Direct injury
CD 81 !
Injury to
podocytes !
Toll –like
receptors !
Hyperisulinemia
and IR !

3.  Cryoglobulin can cause nephrotoxicity by attack the cellular fibronectin in
the mesangial matrix
 Cryoglobulins cause vasculitis by deposition in the small-sized arteries 
fix complement  cause local inflammation and injury
Clinical pictures of renal diseases due to HCV:
 Patients with chronic hepatitis c
 Proteinuria
 Hematuria (microscopic)
 Deterioration of kidney functions
 HTN
 Triad of purpura , asthenia , arthralgia ( GN with cryoglobulinemia)
 The purpura is palpable , which consists of leukocytoclastic vasculitis, this
lesions mostly found in the lower limb or can found anywhere, this
represent small vessel vasculitis
 Low serum C4 ,C1q and CH50 but normal C3
 There are different presentation of renal disease according to types of
glomerulonephritis
Diagnosis
 Laboratory tests +Renal biopsy
 Anti-HVC antibody and HCV RNA in serum
 Elevated serum transaminase in > 70% of patients
 Cryoglobulin can be detected in > 50% of patients
 Rheumatoid factors may be +ve
Pathology
 Renal biopsy show changes according to type of glomerulonephritis
 Membranoproliferative glomerulonephritis type I is the most common
 Or any other types
The Membranoproliferative glomerulonephritis type I
Light microscopy:
 Glomerular hypercellularity
 Increased matrix and mesangial proliferation
 Splitting of capillary basement membranes (double contouring- tram
tracks (
 Intracapillary thrombosis due to cryoglobulin deposition
 Vasculitis and fibrinoid necrosis.

4. Immunofluorescence:
 Deposits of IgG, IgM, and C3 in granular capillary wall distribution and the
mesangium
EM:
 Large subendothelial deposits (different from idiopathic MPGN where the
subendothelial deposits are much smaller )
 These subendothelial deposits are so large they may protrude into the
capillary lumen, causing thrombosis.
Treatment:
The policy of treatment depend on the renal function
 In non- nephrotic , normal renal function  interferon alfa
 In nephrotic syndrome , renal impairment or with cryoglobulinemia
pegylated interferon alfa (1 ug/kg week )+ ribavirin(15 mg/kg/day) for
12 months then short course of low-dose corticosteroids
 In Rapidly progressive renal failure: methylprednisolone (1 g/ day) for
3 days, followed by oral prednisone (60 mg/day) with slow taper over
2-3 months
 Plasma exchange to remove cryoglobulins (3/week for 2 – 3 weeks)
 Rituximab to stop further B cell production (375mg/m 2 weekly for 4
weeks) or in resistance cases
 Cyclophosphamide for 2 – 4 months) 1.5 – 2.0mg/kg daily orally)
 Use erythropoietin to keep Hb>110 g/L (ribavirin causes red cell
fragility)
 ACE-1/ARB to reduce proteinuria ( uPCR<50 mg/mmol) also to control
blood pressure ( aim < 130/80mmHg)