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