HCV in CKD and renal HCV in CKD and renal transplantationtransplantation

Dr. Rania El-shalDr. Rania El-shalMNGHMNGH

• Detection and evaluation of HCV in CKD.• Treatment of HCV infection with CKD.• Diagnosis and management of kidney

diseases associated with HCV infection.• Management of HCV-infected patients

before and after kidney transplantation.

Detection and evaluation of HCV in CKD:

Screening all patients for HCV infection at the time of initial evaluation of CKD.

• HCV ant ibody• PCR (pr e dialysis)- limit s of det ect ion

(10 – 20 I U/ ml).• HD pat ient s ever y 6 mont hs.• HD pat ient s wit h r esolved HCV –

PCR ever y 6 mont hs.• ALT checked mont hly in PCR

negat ive HD pat ient s.• Screen for kidney disease with

urinalysis and estimated glomerular f iltration rate (eGFR).

Treatment of HCV infection in patients with CKD:

Treatment of HCV infection in patients with CKD:

• All CKD patients infected with HCV be evaluated for antiviral therapy.

• interferon-free regimen.

• choice of specific regimen be based on HCV genotype (and subtype), viral load, drug-drug interactions, eGFR category, stage of hepatic fibrosis, kidney and liver transplant candidacy, and comorbidities.

• patients with eGFR > 30 ml/min/1.73 m2 be treated with any licensed DAA-based regimen.

• patients with eGFR < 30 ml/min/1.73 m2 be treated with DAA based regimens, preferentially ribavirin-free.

• HCV genotype 4 the use of grazoprevir/elbasvir or the “2D” regimen (the combination of ritonavir-boosted paritaprevir, ombitasvir regimen) for 12 weeks.

• All kidney transplant recipients infected with HCV treated with a DAA-based regimen.

• Pre-treatment assessment for drug-drug interactions between the DAA-based regimen and other concomitant medications including immunosuppressive drugs in kidney transplant recipients

• calcineurin inhibitor levels be monitored during and after DAA treatment.

Recommendations for Patients With Recommendations for Patients With CKD Stagea 1, 2, or 3CKD Stagea 1, 2, or 3

No dose adjustment is required when using:No dose adjustment is required when using:• Daclatasvir (60 mg)bDaclatasvir (60 mg)b• Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg)Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg)• Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)cDaily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)c• Fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg)Fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg)• Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)• Simeprevir (150 mg)Simeprevir (150 mg)• Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)/Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)/• voxilaprevir (100 mg)voxilaprevir (100 mg)• Sofosbuvir (400 mg)Sofosbuvir (400 mg)

Patients With CKD Stagea 4 or 5 (eGFR Patients With CKD Stagea 4 or 5 (eGFR <30 mL/min or End-Stage Renal Disease<30 mL/min or End-Stage Renal Disease((

• Daily fixed-dose combination of elbasvir Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) 1a, 1b, 4 for (50 mg)/grazoprevir (100 mg) 1a, 1b, 4 for 12 ws.12 ws.

• Daily fixed-dose combination of Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) glecaprevir (300 mg)/pibrentasvir (120 mg) 1, 2, 3, 4, 5, 6 for 8 ws.1, 2, 3, 4, 5, 6 for 8 ws.

Diagnosis and management of kidney diseases associated with HCV infection.

Glomerular diseases associated with HCV:• MPGN MC• Membranous nephropathy• acute proliferative GN• focal segmental glomerulosclerosis • Ig Anephropathy • thrombotic microangiopathy • rapidly progressive nephritis• fibrillary GN• immunotactoid glomerulopathy

MPGN MC

• Nephritic syndrome.• Non-nephrotic proteinuria or hematuria and/or

reduced eGFR. • Acute nephritic or nephrotic syndrome • Arterial hypertension is frequent (affecting >

50% of patients at the time of diagnosis) and is often resistant to anti-hypertensive drugs - the severity of hypertension often mirrors the severity of kidney disease.

• Around 10% of patients present oliguric kidney

• Laboratory parameters reveal:• circulating cryoglobulins- • Serum anti-HCV antibody and HCV RNA.• Positive rheumatoid factors are usually

present .• serum C3 and C4 levels are frequently

low.• normal AST and ALT levels or only a

modest elevation in liver enzymes in some ptn.

• Distinctive features• sub-endothelial deposits• Hypercellularity• The glomerular basement membrane

often shows double contours• On electronic microscopy, large

subendothelial deposits are present

• kidney biopsy be performed in HCV-infected patients with clinical evidence of glomerular disease.

• patients with HCV-related glomerular disease showing stable kidney function and/or non-nephrotic proteinuria be treated initially with DAA.

• Patients with cryoglobulinemic flare, nephrotic syndrome, or progressive kidney failure be treated with both DAA and immunosuppressive agents and/or plasma-exchange.

• Immunosuppressive therapy in patients with histologically active HCV-associated glomerular disease who do not respond to antiviral therapy, particularly those with cryoglobulinemic kidney disease.

• Rituximab as the first-line immunosuppressive treatment. (375 mg/m2 weekly for 4 weeks)

• or cyclophosphamide (2 mg/kg/day for 2-4 months) plus methylprednisolone pulses 0.5-1 g/day for 3 days.

Management of HCV-infected patients before and after kidney transplantation:

• HCV-infected kidney-transplant candidates be evaluated for severity of liver disease and, if indicated, portal hypertension prior to acceptance for an isolated kidney or combined kidney-liver transplantation.

• HCV-infected patients with compensated cirrhosis (without portal hypertension) undergo isolated kidney transplantation.

• HCV-infected patients with decompensated cirrhosis for combined liver-kidney transplantation and to defer HCV treatment until after transplantation.

• All HCV-infected patients who are candidates for kidney transplantation, they be considered for antiviral therapy, either before or after transplantation.

• HCV-infected kidney-transplant candidates with a living kidney donor, they can be considered for treatment before or after transplantation according to HCV genotype and anticipated timing of transplantation.

• After the assessment of liver fibrosis, potential HCV-positive living kidney donors who do not have cirrhosis should undergo HCV treatment before donation; they can be accepted for donation if they achieve SVR and remain otherwise eligible to be a donor

• All conventional current induction and maintenance immunosuppressive regimens can be considered for use in HCV-infected kidney transplant recipients.

• patients previously infected with HCV who achieved SVR before transplantation be tested by PCR 3 months after transplantation or if liver dysfunction occurs.

• Untreated HCV-positive kidney-transplant recipients should have the same liver disease follow-up as HCV-positive non-transplant patients.

• HCV infected kidney transplant recipients should be tested at least every 6 months for proteinuria.

• patients who develop new onset proteinuria (either urine protein/creatinine ratio > 1 or 24-hour urine protein > 1 g on two or more occasions) have an allograft biopsy with immunofluorescence and electron microscopy included in the analysis.

• Treatment with a DAA regimen in patients with post-transplant HCV-associated glomerulonephritis.

Proposed strategy in HCV infected kidney Proposed strategy in HCV infected kidney transplant candidatetransplant candidate

SummarySummary::

• Renal function, including an estimation of CrCl or GFR, Renal function, including an estimation of CrCl or GFR, must be assessed before initiating any hepatitis C must be assessed before initiating any hepatitis C treatmenttreatment..

• Specific recommendation for the treatment of pateeints Specific recommendation for the treatment of pateeints with severe renal disease, including those with end-stage with severe renal disease, including those with end-stage renal disease.renal disease.

• Patients with hepatitis C infection who require renal Patients with hepatitis C infection who require renal transplantation should be evaluated for hepatitis C transplantation should be evaluated for hepatitis C treatment; the treatment of hepatitis C prior to renal treatment; the treatment of hepatitis C prior to renal transplantation is strongly preferred over treatment of transplantation is strongly preferred over treatment of hepatitis C post renal transplantation.hepatitis C post renal transplantation.

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