Download For patients with genotype 1b infection and CrCl below 30 mL/min

HCV&HBV
IN HEMODIALYSIS AND TRANSPLANT PATIENTS
Dr.L.Davoodi
Mazandaran University of Medical Sciences
‫معرفی یک بیمار‪:‬‬
‫بیمارآقای ‪ 43‬ساله که بعلت نارسایی کلیوی در زمینه هایپرتنشن و سنگ کلیوی که‬
‫بمدت چند سال دیالیز می شده است و کاندید پیوند کلیه می باشد از طرف نفرولوژیست‬
‫با آزمایش آنتی بادی هپاتیت سی مثبت ارجاع می شود‪.‬‬
‫آیا دراین بیمار درمان قبل از پیوند یا بعد از پیوند انجام شود؟با چه داروهایی؟ آیا‬
‫هپاتیت (با درجات مختلف درگیری کبدی) منع پیوند کلیه است ؟‬
chronic viral hepatitis, 400 million
Approximately 170 million HCV (2.35% of the total world
population ).
In dialysis patients, the prevalence of HCV infection
decreased dramatically over the last 10 years. In 2004 the
HCV antibody prevalence was14.7% but now estimated less
than 5%
HCV impacts general outcomes in chronic kidney
disease, dialysis or transplanted patients.
HCV-ASSOCIATED RENAL DISEASE POSTTRANSPLANTATION
 Posttransplant proteinuria
 Membranoproliferative glomerulonephritis
 A renal thrombotic microangiopathy (RTMA) , particularly
with anticardiolipin antibodies
 Acute transplant glomerulopathy
 Chronic transplant glomerulopathy
 Membranous nephropathy
 Mixed cryoglobulinemia vasculitis (CryoVas)
Proteinuria has been used as a marker of disease in the renal
allograft among anti-HCV positive transplant recipients.
baseline protein-to-creatinine ratios and urinalyses within the
first two weeks after transplantation. Subsequently, patients
should be tested at least every three to six months. patients
who develop new onset proteinuria (urine protein/creatinine
ratio >1 or 24-hour urine protein greater than 1 g on two or
more occasions) or microscopic hematuria without other
identifiable cause should undergo an allograft biopsy.
treatment with ACEI/ARB has been found to
reduce proteinuria and slow down the
progression of chronic kidney allograft disease
Immunocompromised patients , Patients on hemodialysis,
transplant recipients, and AIDS have a much higher rate of
false negative EIAs than immunocompetent patients . Thus,
HCV RNA testing should be performed in all patients who are
immunocompromised and EIA-2 negative if there is clinical
suspicion of infection. EIA-3 may be more sensitive than EIA-2
in hemodialysis patients.
In transplanted patients,
immunosuppression has been associated
with an increase of serum HCV-RNA levels
CKD always impacts the treatment of CHC negatively because
of the poorer drug tolerance, higher prevalence of side effects
and complexity of drug dosage adaptation. Hepatitis C
treatment has long been offered through peginterferon alpha
associated with ribavirin with very poor tolerance and a high
prevalence of anemia and depressive syndrome leading to
anticipated resuming of therapy.
New DAAs offer dramatically improved efficacy in the general
population.
IFNa has pleiotropic effects including antiproliferative and
immunomodulatory properties . IFNa also induces cytokine
gene expression, increased cell surface expression of HLA
antigens, and enhanced function of natural killer cells,
cytotoxic T cells, and monocytes.
These immunostimulant effects can result in enhanced
allograft rejection
At present, we do not use IFNa in transplant recipients with
HCV-associated renal disease.
By comparison, pretransplant IFNa treatment of HCV
infection in dialysis patients waiting for a kidney transplant
may modify the incidence of HCV-associated kidney
allograft disease in the posttransplant period. This also
seems to be a safer strategy since it would eliminate the
need of IFNa treatment of HCV infection after
TRANSPLANT.
clearance of ribavirin is impaired in patients with renal
dysfunction, and that ribavirin is not recommended for
patients with a creatinine clearance below 50 mL/min
RBV should only be given if the baseline hemoglobin
level is greater than 10 g/dl For patients with moderate
renal impairment (GFR <30) RBV dosing should be 200
mg/d.
HCV positive status alone should not be considered a
contraindication for renal transplantation
Liver damage as determined by histologic severity is a strong
predictor of liver failure and death after transplantation.
in HCV positive patients without evidence of liver disease, we
suggest that such patients should be allowed to make an
informed choice of staying on dialysis or undergoing
transplantation. However, transplant recipients can have
histological evidence of liver disease in the absence of elevated
serum ALT levels
A safer strategy might be to treat chronic
hepatitis C in dialysis patients, who are
considered transplant candidates, prior to
transplantation. IFNa therapy of HCV-infected
patients undergoing hemodialysis seems to have
a beneficial effect on the course of liver disease
following renal transplant, regardless of the
virological response.now DAAs can be the drug
of choice.
New strategies will now emerge with regard to HCV
treatment before or after renal transplantation depending
also on the availability of a living donor or not. In case of a
living donor, it has been proposed that DDA’s treatment
should occur before transplantation in order to obtain SVR12.
When there is no living donor available, some centers will
offer an HCV-positive graft to the patient and begin DAA
treatment after transplantation, therefore reducing waiting
times significantly.
EASL 2015 Hepatitis C guidelines in hemodialysis patients:
Simeprevir, daclatasvir and the combination of ritonavirboosted paritaprevir, ombitasvir and dasabuvir are cleared
by hepatic metabolism and can be used in patients with
severe renal disease
AASLD 2015:
For patients with mild to moderate renal impairment
(GFR>=30)
no dosage adjustment is required when using sofosbuvir,
simeprevir, a fixed-dose combination of ledipasvir (90
mg)/sofosbuvir (400 mg) or fixed-dose combination of
paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg)
plus twice-daily dosed dasabuvir (250 mg) to treat or
retreat HCV infection in patients with appropriate
genotypes
•For patients with genotype 1b infection and CrCl below 30 mL/min
for whom the urgency to treat is high and treatment has been
elected before kidney transplantation, daily fixed-dose combination
of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus
twice-daily dosed dasabuvir (250 mg) for 12 weeks is a
Recommended regimen.
•For patients with HCV genotype 2, 3, 5, or 6 infection and CrCl
below 30 mL/min for whom the urgency to treat is high and
treatment has been elected before kidney transplantation, PEG-IFN
and dose-adjusted ribavirin** (200 mg daily) is a Recommended
regimen.
Recommended Regimens for Patients with Severe
Renal Impairment, Including Severe Renal Impairment
(Creatinine Clearance [CrCl] <30 mL/min) or End-Stage
Renal Disease (ESRD)
•For patients with genotype 1a, or 1b, or 4 infection
and CrCl below 30 mL/min, for whom treatment has
been elected before kidney transplantation, daily fixeddose combination of elbasvir (50 mg)/grazoprevir
(100mg) for 12 weeks is a Recommended regimen.
Alternative Regimen for Genotype 1a-infected
Patients with CrCl Below 30 mL/min
•For HCV genotype 1a infection, daily fixed-dose
combination of paritaprevir (150 mg)/ritonavir (100
mg)/ombitasvir (25 mg) plus twice-daily dosed
dasabuvir (250 mg) and dose-adjusted ribavirin**
(200 mg daily) for 12 weeks is an Alternative regimen
HBV & CKD
 In general, dialysis patients with positive (HBsAg) who are
being considered for kidney transplantation should
undergo liver biopsy .
 A kidney transplant is generally contraindicated if cirrhosis
is noted .
 However, in patients with compensated cirrhosis may be
considered for kidney transplantation.
 If moderate to severe hepatitis and detectable replication
(positive HBeAg or HBV DNA) are found, antiviral therapy
prior to transplantation may be indicated
reactivation of HBV replication (increase or appearance of serum
HBV )may occur after kidney transplantation secondary to the
use of immunosuppressive therapy. Reactivation of HBV
replication is more likely to occur in patients who were HBeAg
positive or had detectable serum HBV DNA prior to transplant;
however, reactivation can also occur in patients who were HBeAg
negative or had undetectable serum HBV DNA prior to
transplant. Reactivation of HBV replication has also been
reported in those who were HBsAg-negative and anti-HBc
positive. With reactivation, an increase in serum HBV DNA levels
usually precedes an increase in ALT levels. In some patients,
reactivation may result in hepatitis flares and, rarely, hepatic
failure and death
Neither telaprevir nor boceprevir has been
adequately studied in organ transplant
recipients. Telaprevir has been shown to
significantly increase the concentrations of
both cyclosporine and tacrolimus . We
recommend NOT using telaprevir among
renal transplant recipients until studies
demonstrating its safety have been done.
•patients with detectable HBV DNA prior to kidney transplantation, we
suggest prophylactic antiviral therapy prior to or at the time of surgery. Our
preferred antiviral agent is entecavir , which has lower nephrotoxicity than
tenofovir
•those infected with HBV but without detectable HBV DNA just prior to
transplantation, we suggest a preemptive approach. This approach places an
emphasis on minimizing drug exposure and the risk of drug resistance. We
monitor serum HBV DNA every three months for the first year and every six
months thereafter. Antiviral therapy is initiated when serum HBV DNA
becomes persistently detectable or increases progressively.
• If frequent monitoring of serum HBV DNA levels is not feasible, we
recommend a prophylactic approach, at least for the first one to two years
post-transplantation
in patients who are anti-HBc positive and HBs antigen negative
are at lower risk of reactivation post-transplantation. Thus, most
clinicians check HBV DNA levels only if ALT levels are increased.
However, some clinicians would monitor HBV DNA levels
regardless of ALT and use a preemptive approach based upon
HBV DNA levels alone.
adefovir
Cl cr ≥50 mL/minute: No dosage adjustment necessary
(10 mg/d)
Cl cr 20-49 mL/minute: 10 mg every 48 hours
Cl cr 10-19 mL/minute: 10 mg every 72 hours
Hemodialysis: 10 mg every 7 days (following dialysis)
Lamivudin: 100 mg/d in GFR >50
Cl cr 30-49 mL/minute: Administer 100 mg first dose, then 50 mg
once daily.
Cl cr 15-29 mL/minute: Administer 100 mg first dose, then 25 mg
once daily.
Cl cr 5-14 mL/minute: Administer 35 mg first dose, then 15 mg once
daily.
Cl cr <5 mL/minute: Administer 35 mg first dose, then 10 mg once
daily.
tenofovir
Cl cr ≥50 mL/minute: No dosage adjustment necessary. 300mg/d
Cl cr 30-49 mL/minute: 300 mg every 48 hours
Cl cr 10-29 mL/minute: 300 mg every 72-96 hours
Cl cr <10 ml ?
Hemodialysis: 300 mg following dialysis every 7 days
entecavir
Nucleoside treatment naive: 0.5 mg once daily
Lamivudine-resistant or telbivudine-resistant mutations): 1 mg once
daily
Decompensated liver disease: 1 mg once daily
Cl cr ≥50 mL/minute: No dosage adjustment necessary.
Cl cr 30-49 mL/minute: Administer 50% of usual dose daily or administer
the normal dose every 48 hours
Cl cr 10-29 mL/minute: Administer 30% of usual dose daily or administer
the normal dose every 72 hours
Cl cr <10 mL/minute (including hemodialysis and CAPD): Administer 10%
of usual dose daily or administer the normal dose every 7 days;
administer after hemodialysis
telbivudine
Cl cr ≥50 mL/minute: No dosage adjustment :600mg/d
Cl cr 30-49 mL/minute: 600 mg every 48 hours
Cl cr <30 mL/minute (not requiring dialysis): 600 mg every 72
h
End-stage renal disease: 600 mg every 96 hours
Hemodialysis: Administer after dialysis session
References:
AASLD 2016
EASL 2015
WJG 2015
MANDEL 2015
UPTODATE 2016