Hepatitis C in kidney transplantation
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Transcript of Hepatitis C in kidney transplantation
Hepatitis C in Kidney Transplantation
Salwa Ibrahim, MD FRCP EdinCairo University
Cairo-Preston Renal ISN Transplant Workshop
5-6 September 2015
Main Issues of HCV in kidney transplantation
HCV Prevalence in Egypt
Patient and graft survival
Effect on the kidney
Effect on the liver
Antiviral treatment
HCV donor
HCV Prevalence in Egypt
• Egypt has the highest prevalence of hepatitis C virus (HCV) in the world, estimated nationally at 14.7%
• Among dialysis patients between 50-90%
Patient and graft survival
Gentil MA et al. Nephrol Dial Transplant. 1999;14:2455-2460.
Graft SurvivalPatient Survival
HCV infection is associated with lower graft and
recipient survival
Serum creatinine showed highermean values in HCV+ vs HCV− patients from the
second year
Mean values of eGFR were lower in HCV+ vs HCV− patients
from the second year post-transplant
Mean values of proteinuria were higher from the firstyear in HCV+ vs HCV− patients
New Onset Diabetes Mellitus (NODAT)
Survival is better compared to dialysis
Renal Transplant in HCV cases
• Renal transplantation is associated with a 68% reduction in long-term mortality compared to remaining on the waiting list
J Am Soc Nephrol 22: 1152–1160, 2011
Effect on the graft
Kidney diseases associated with HCV infection
• Membranoproliferative GN (Cryo+ve /-ve)
• Membranous GN• Mesangioproliferative GN
Thrombotic Microangiopathy
Effect on the liver
Hepatoma and cirrhosis in HBV, HCV infection or co-infection among renal transplantation patients
477 cases were followed-up from 1984 to 1999
HBV-/HCV-HBV-/HCV+
HBV+/HCV-HBV+/HCV+
Prevalence(N)
58.5%(279)9.9%(47)
28.5%(136)3.1%(15)
Hepatoma
1.4%4.4%6.4%6.7%
Cirrhosis
3.2%6.6%
21.3%20%
Lee WC, et al. Am J Nephrol. 2001,21:300-6
Antiviral therapy
• Remarkable strides have been made in treating chronic hepatitis C in the last few years
Pre vs. post transplant treatment
• HCV-associated liver damage may be accelerated by immunosuppression.
• For this reason, antiviral therapy should be considered for all haemodialysis patients who will be candidates for renal transplantation
EASL Recommendations on Treatment of Hepatitis C 2015
Pre-transplant treatment
Assessment of HCV disease activity
HCV RNA
• HCV RNA detection and quantification should be made by a sensitive assay (lower limit of detection of <15 IU/ml)
• The HCV genotype must be assessed prior to treatment initiation and will determine the choice of therapy
EASL Recommendations on Treatment of Hepatitis C 2015
Liver disease severity
• Liver disease severity should be assessed prior to therapy
• Identifying patients with cirrhosis is of particular
importance, as their prognosis is altered and their treatment regimen may be adapted
EASL Recommendations on Treatment of Hepatitis C 2015
Assessment of disease severity
• Assessment of the stage of fibrosis is not required in patients with clinical evidence of cirrhosis.
• Patients with cirrhosis need surveillance for HCC
EASL Recommendations on Treatment of Hepatitis C 2015
Fibro Test• FIBROSCAN (also known as transient elastography) poses
the greatest competition to biopsy • it is non-invasive, less expensive, and (arguably) equally
accurate in measuring degree of liver inflammation and fibrosis, particularly in the higher end of the Metavir scale (Stages 3 and 4)
Antiviral therapy
When to initiate treatment
• Immediate treatment for those patients with advanced fibrosis, those with compensated cirrhosis, and patients with severe extrahepatic hepatitis C
• HCV related glomerulonephritis as cause of ESRD
20142014
ESRD
• PEG-IFN (2a) 135 µg/wk or PEG-IFN (2b) 1 µg/kg/wk or standard IFN 3 mU 3x/wk
• RBV 200 mg/daily or thrice weekly
• Duration of therapy (24-48 )Weeks
• SVR ~ 55% -66%
2014 20082008
Direct acting antiviral(DAAs)
SOFOSBUVIR
• 80% of sofosbuvir is renally excreted
• Can not be used in GFR < 30 ml/min
ledipasvir
• Biliary excretion is the major route of excretion
Simeprevir
• Eliminated by biliary excretion
• No dose reduction in kidney disease
Daclatasvir
• Eliminated in faeces (90%)
• No dose reduction in kidney disease
Interferon free regimen for Genotype 4
• Sofosbuvir+ribavirin
• Sofosbuvir+Simeprevir (400mg+150 mg)
• Sofosbuvir+Simeprevir+ribavirin
• Sofosubvir+Ledipasvir (90 mg/400 mg (Harvoni)
• Sofosubvir+Daclatasvir
Viekira Pack+ ribavirin
• Viekira Pak is drug cocktail that includes a combination pill which contains the antiviral drugs ombitasvir, paritaprevir and ritonavir (12.5/75/50 mg) tablets, along with a tablet of dasabuvir (250 mg)
• No dosage adjustment of Viekira Pak is required in patients with mild, moderate or severe renal impairment
Post transplant care
• Monthly liver functions for 6 months then every 3 months
• Referral to hepatologist with worsening trends of liver enzymes (HCV RNA,US exam, Fibroscan, liver biopsy )
KDIGO 2008
Indications of urgent treatment post transplant : recurrent HCV glomerulopathy, severe cholestatic hepatitis, advanced histologic
stages of liver disease
Should we accept HCV positive donor?
NO
HCV positive donorAfter treatment
Can donate kidney after treatment provided:
• HCV RNA Negative for 24 weeks• Normal liver functions• Normal liver U/S
Hepatitis C in Kidney Transplantation
Salwa Ibrahim, MD FRCP EdinCairo University
Cairo-Preston Renal ISN Transplant Workshop
5-6 September 2015