Dr rania alshal hcv and ckd

2. HCV in CKD and renalHCV in CKD and renal
transplantationtransplantation
Dr. Rania El-shalDr. Rania El-shal
MNGHMNGH

3. • 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.

4. Detection and evaluation of
HCV in CKD:
Screening all patients forHCV infection at
the time of initial evaluation of CKD.
• HCV ant ibody
• PCR (pre dialysis)- limit s of det ect ion
(10 – 20 I U/ ml).
• HD pat ient s every 6 mont hs.
• HD pat ient s wit h resolved HCV –
PCR every 6 mont hs.
• ALT checked mont hly in PCR

5. Treatment of HCV infection in patients with CKD:

7. Treatment of HCV infection in patients with
CKD:
• All CKDpatients infected with HCV be
evaluated forantiviral therapy.
• interferon-free regimen.
• choice of specific regimen be based on
HCV genotype (and subtype), viral load,
drug-drug interactions, eGFRcategory,
stage of hepatic fibrosis, kidney and liver
transplant candidacy, and comorbidities.

8. • 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
orthe “2D” regimen (the combination of
ritonavir-boosted paritaprevir, ombitasvir
regimen) for12 weeks.
• All kidney transplant recipients infected with
HCV treated with a DAA-based regimen.

9. • Pre-treatment assessment fordrug-drug
interactions between the DAA-based
regimen and otherconcomitant
medications including immunosuppressive
drugs in kidney transplant recipients
• calcineurin inhibitorlevels be monitored
during and afterDAA treatment.

10. Recommendations for Patients WithRecommendations 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)

11. Patients With CKD Stagea 4 or 5 (eGFRPatients 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 elbasvirDaily 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 ofDaily 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.

13. 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

14. 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

15. • 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

16. • Distinctive features
• sub-endothelial deposits
• Hypercellularity
• The glomerular basement membrane
often shows double contours
• On electronic microscopy, large
subendothelial deposits are present

17. • kidney biopsy be performed in HCV-infected
patients with clinical evidence of glomerular
disease.
• patients with HCV-related glomerulardisease
showing stable kidney function and/ornon-
nephrotic proteinuria be treated initially with
DAA.
• Patients with cryoglobulinemic flare, nephrotic
syndrome, orprogressive kidney failure be
treated with both DAA and immunosuppressive
agents and/orplasma-exchange.

18. • Immunosuppressive therapy in patients
with histologically active HCV-associated
glomerulardisease 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)

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

20. Management of HCV-infected patients before and
afterkidney transplantation:
• HCV-infected kidney-transplant candidates be
evaluated forseverity of liverdisease and, if
indicated, portal hypertension priorto
acceptance foran isolated kidney orcombined
kidney-livertransplantation.
• HCV-infected patients with compensated
cirrhosis (without portal hypertension) undergo
isolated kidney transplantation.

21. • HCV-infected patients with
decompensated cirrhosis forcombined
liver-kidney transplantation and to defer
HCV treatment until aftertransplantation.
• All HCV-infected patients who are
candidates forkidney transplantation,
they be considered forantiviral therapy,
eitherbefore oraftertransplantation.

22. • HCV-infected kidney-transplant candidates with
a living kidney donor, they can be considered
fortreatment before oraftertransplantation
according to HCV genotype and anticipated
timing of transplantation.

23. • Afterthe assessment of liverfibrosis,
potential HCV-positive living kidney
donors who do not have cirrhosis should
undergo HCV treatment before donation;
they can be accepted fordonation if they
achieve SVRand remain otherwise
eligible to be a donor

24. • All conventional current induction and
maintenance immunosuppressive regimens can
be considered foruse in HCV-infected kidney
transplant recipients.
• patients previously infected with HCV
who achieved SVRbefore transplantation
be tested by PCR3 months after
transplantation orif liverdysfunction
occurs.

25. • Untreated HCV-positive kidney-transplant
recipients should have the same liverdisease
follow-up as HCV-positive non-transplant
patients.
• HCV infected kidney transplant recipients
should be tested at least every 6 months for
proteinuria.

26. • patients who develop new onset
proteinuria (eitherurine
protein/creatinine ratio > 1 or24-hour
urine protein > 1 g on two ormore
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.

27. Proposed strategy in HCV infected kidneyProposed strategy in HCV infected kidney
transplant candidatetransplant candidate

28. 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 Cmust be assessed before initiating any hepatitis C
treatmenttreatment..
• Specific recommendation for the treatment of pateeintsSpecific recommendation for the treatment of pateeints
with severe renal disease, including those with end-stagewith severe renal disease, including those with end-stage
renal disease.renal disease.
• Patients with hepatitis C infection who require renalPatients with hepatitis C infection who require renal
transplantation should be evaluated for hepatitis Ctransplantation should be evaluated for hepatitis C
treatment; the treatment of hepatitis C prior to renaltreatment; the treatment of hepatitis C prior to renal
transplantation is strongly preferred over treatment oftransplantation is strongly preferred over treatment of
hepatitis C post renal transplantation.hepatitis C post renal transplantation.

29. Thank youThank you