HCV INFECTION AND

RENAL DISEASE
DR KULEESHA KODISINGHE

OVERVIEW

Renal manifestations of HCV infection

HCV infection in CKD patients
Renal transplantation in HCV infection

RENAL MANIFESTATIONS OF HCV

INFECTION
Several types of glomerulonephritis have been associated with HCV:

MCGN - most common type; may occur with or without cryoglobulinemia

Membranous GN

FSGS

IgA nephropathy

PAN

Fibrillary and immunoactoid glomerulopathies

These may present as nephritic syndrome or nephrotic syndrome

The course of renal disease may be variable. In about 30% renal function may be stable for many years, 20%
may have recurrent episodes and about 15% may become dialysis dependent

RENAL MANIFESTATIONS OF HCV

INFECTION - TREATMENT

Antiviral agents
Immunosuppression
Plasma exchange

Antiviral agents

Treatment is mainly based on antiviral agents

Treatment is similar to standard clinical practice guidelines for HCV infection
Interferon therapy may result in exacerbation of vasculitis, and therefore treatment should be restricted
to those with overt symptoms

Dosing of IFN and ribavirin should be adjusted to the degree of kidney function

Immunosuppression and plasma exchange

Should be instituted before initiation of antiviral therapy in patients with severe
cryoglobulinemic vasculitis or glomerulonephritis
Immunosuppression with short course of corticosteroids +/- cyclophosphamide or
rituximab
Antiviral therapy should be commenced once the acute illness has improved

HCV INFECTION IN CKD PATIENTS

The prevalence of HBV infection among patients on maintenance haemodialysis in the developed world
is currently low (2-20%) but remains high (70%) in developing countries
Transmission may occur from:

Blood transfusions

Nosocomial contamination
Isolation of HCV-infected patients during dialysis or the use of dedicated dialysis machines are not
recommended, unlike in HBV

Transplantation of an infected renal graft

Clinical implications
More rapid decline in renal function
Higher all-cause mortality and cardiovascular mortality
ALT values may not be a useful indicator of liver damage - ALT values may be normal despite histological
evidence of liver inflammation . Hence, liver biopsy may be required for CKD patients with HCV
infection to assess the degree of liver damage

HCV INFECTION IN CKD PATIENTS MANAGEMENT

Indications for antiviral therapy:

Decision to treat HCV infection in the CKD patients should be based on the potential benefits and risks
of therapy - life expectancy, candidacy for kidney transplantation, comorbidities
All candidates for solid-organ transplantation to achieve viral eradication by the time of transplantation

Use of antiviral agents in CKD:

IFN causes more side effects in dialysis patients than among nonuremic patients. The side effect profile is
also somewhat different - in addition to early flu-like symptoms, patients may experience severe late side
effects, especially cardiovascular effects (angina, cardiomyopathy), hemorrhagic strokes and
ophthalmological disorders
Standard IFN has fewer side effects and equal efficacy to peg-IFNa among haemodialysis patients, and
has been recommended by an international group of experts at 3mU three times a week

 Ribavirin is eliminated through the kidneys and is not removed by dialysis. The result is an increased
severity of hemolytic anemia among persons in whom anemia is already a problem
Ribavirin should be used at GFR levels <50 ml/min very carefully, at very low doses, with weekly
monitoring of hemoglobin levels, possibly with increased dosage of erythropoietin and intravenous iron
supplementation to boost erythropoietin activity

 Evidence concerning triple therapy in CKD population is not currently available

PIs (telaprevir and boceprevir) undergo extensive hepatic metabolism with minimal urinary excretion;
thus no dose adjustment is required in patients with renal insufficiency

Therapeutic regimen varies with the severity of kidney disease:

CKD stages 1 and 2 - can be treated with the same regimen as in persons without kidney disease
CKD stages 3-5# peginterferon alfa-2a 135 g weekly (peginterferon alpha-2b 1 g/kg weekly) +
ribavirin 200-800 mg/d in 2 divided doses (started at low dose and increased gradually)
CKD stage 5D# peginterferon alfa-2a or 2b as above; ribavirin may be used in a markedly reduced dose
(200 mg/d to 200 mg/EOD)
#Very

limited data exist about dual antiviral therapy in CKD stage 35; monotherapy with IFN / PegIFN can
be given when the risk of using ribavirin is thought to outweigh the benefit, but in the absence of ribavirin
SVR rates are substantially low

RENAL TRANSPLANTATION IN HCV

INFECTION
Positive anti-HCV serologic status after kidney transplantation may result in:
Shorter graft survival
More frequent de novo glomerulonephritis
More frequent NODAT
More frequent and more rapid progression of liver disease to cirrhosis and HCC
Possibility of rapidly evolving to hepatocellular insufficiency

Chronic liver disease increases the risk of hepatotoxicity during treatment with immunosuppressants

RENAL TRANSPLANTATION IN HCV

INFECTION - MANAGEMENT
Type of transplantation
Patients can be candidates for solitary renal transplantation only if they do not have cirrhosis. Patients
with cirrhosis require simultaneous liver and kidney transplantation
In compensated cirrhotic patients who achieve an SVR, the liver biopsy should be repeated and in the
case of reversal of cirrhosis, renal transplantation alone is feasible
Liver biopsy may be required for CKD patients with HCV infection to assess the degree of liver damage

Therapy in post-renal transplantation HCV infection:

Interferon is not recommended post-KT due to low efficacy and high risk of and should be considered
only for persons who develop fibrosing cholestatic hepatitis or life-threatening vasculitis (in these
patients, the risk of treating justifies the possible loss of the allograft)
In the absence of other available treatments and due to its acceptable safety profile, ribavirin
monotherapy (prescribed cautiously at gradually increasing doses) may be considered. Ribavirin
monotherapy frequently restores normal transaminase levels and sometimes lowers viremia, but
without suppressing viral replication

Monitoring for liver complications

HCC screening with USS - every 3 months in cirrhotic patients and every 612 months in non-cirrhotic
patients
Evaluation of the impact of hepatitis on the liver by liver biopsy and non-invasive tests of fibrosis
every 3-5 years

REFERENCES
Fabrizio Fabrizi, Alessio Aghemo, Piergiorgio Messa. Hepatitis C treatment in
patients with kidney disease. Kidney International. 2013;84: 874879
Elias C Chacko, Soondal Koomar Surrun, T P Mubarack Sani, Joseph M Pappachan.
Chronic viral hepatitis and chronic kidney disease. Postgraduate Medical Journal.
2010;86:486-492
Anais Vallet-Pichard, Hlne Fontaine, Vincent Mallet, Stanislas Pol. Viral hepatitis
in solid organ transplantation other than liver. Journal of Hepatology 2011;55:474
482
Ira M. Jacobson, Patrice Cacoub, Luigino dal Maso, Stephen A. Harrison, Zobair M.
Younossi. Manifestations of Chronic Hepatitis C Virus Infection Beyond the Liver.
Clinical Gastroenterology and Hepatology. 2010;8:10171029
AASLD and EASL guidelines on Hepatitis C

THANK YOU