HCV INFECTION AND RENAL DISEASE

DR KULEESHA KODISINGHE

• Renal manifestations of HCV infection

• HCV infection in CKD patients

• Renal transplantation in HCV infection

OVERVIEW

• 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

• Antiviral agents

• Immunosuppression

• Plasma exchange

RENAL MANIFESTATIONS OF HCV INFECTION - TREATMENT

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

• 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

HCV INFECTION IN CKD PATIENTS

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

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

HCV INFECTION IN CKD PATIENTS - MANAGEMENT

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 µg weekly (peginterferon alpha-2b 1 µg/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 3–5; 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

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

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

RENAL TRANSPLANTATION IN HCV INFECTION - MANAGEMENT

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 6–12 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

• Fabrizio Fabrizi, Alessio Aghemo, Piergiorgio Messa. Hepatitis C treatment in patients with kidney disease. Kidney International. 2013;84: 874–879

• 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, Hélène 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;8:1017–1029

• AASLD and EASL guidelines on Hepatitis C

REFERENCES

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