Hepatitis C virus (HCV) infection is linked to various renal diseases, often caused by the virus itself, treatment drugs, or advanced liver cell failure. Common renal complications include cryoglobulinemia-associated membranoproliferative glomerulonephritis and other forms like interstitial nephritis and focal segmental glomerulosclerosis, resulting in symptoms such as proteinuria and hematuria. Treatment varies based on renal function, with options ranging from interferon therapy to plasma exchange and corticosteroids to manage complications.

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)