Management of hcv_in_ckd

Management Of HCV In CKD Patient

Dr.Ayman Sabri Abd El Badie

Nephrology specialistNew Mansoura General Hospital

(NMGH)

ISN Ambassador Educational Program Meniet El Nasr Hospital Thursday, 19 January, 2017

Introduction

Hepatitis C virus (HCV) isa small single-strandedRNA virus with a lipidenvelope (E) containingglycoproteins (E1 andE2) and a core with agenome consisting of9600 nucleotides.

ISN Ambassador Educational Program Meniet El Nasr Hospital Thrsday, 19 January, 2017ary, 2017

ISN Ambassador Educational Program Meniet El Nasr Hospital Thursday, 19 January, 2017ary, 2017

The genetic sequence of HCV is characterized bya high rate of spontaneous mutations, withmajor implications for escape from the humanimmune system and the development of aneffective vaccine.


HCV isolates are classified into sixdistinct genotypes depending on

sequence homology.


EPIDEMIOLOGY

The WHO estimates that HCV infection affects 130 to 170 million people worldwide.

Egypt has the highest HCV prevalence rate in the world, estimated nationally about 15 % of the adult population.


Prevalence of HCV


HCV related renal disease

MPGNMembranous

PANOthers

- FSGS-IgA nephropathy-Postinfectious glomerulonephritis-Immunotactoid glomerulopathy- Fibrillary glomerulonephritis.

HCV related renal disease



Management

It is suggested that the decision to treat bebased on the potential benefits and risks oftherapy, including life expectancy, candidacyfor kidney transplantation, andcomorbidities.


Benefits of treatment

• Prevention of HCV complication as HCC , Lymphoma

• Reduced morbidity :- Liver disease.- Extra hepatic manifestation.- Lymph proliferative disease.- Cardiovascular complication.

• Improved survival on hemodialysis.• preparation for transplantation.• Elimination of disease dissemination.


INF ± Ribavirin





Direct acting Anti Viral Drugs


Direct acting Anti Viral Drugs

Trade name

GenericName

SovaldiSofosbuvir

HarvoniLedipasvir / sofosbuvir

OlysioSimeprevir

DaklinzaDaclatasvir

QuerevoParitaprevir /ritonavir / ombitasvir


Mechanism of action




The Monthly DNG Meeting Meynet El Nasr Hospital Friday, 22 April, 2016

eGFR

Native Kidney Transplanted Kidney

> 30 ml/min/1.73 m2

Querevo + Ribavirin 1000mg daily if < 75 kg & 1200mg if >75kg

Harvoni + Ribavirin 1000mg daily if < 75 kg & 1200mg if >75kg

Harvoni + Ribavirin 1000mg daily if < 75 kg & 1200mg if >75kg

Daklinza 60 mg + Sovaldi 400mg + Ribavirin daily fixed dose 600mg

Olysio 150mg + Sovaldi 400mg + Ribavirin if cirrhosis 1000mg daily if < 75 kg & 1200mg if >75kg

12 weeks

12 weeks OR24 weeks in presence of cirrhosis

24 weeks

Selected protocol

Alternative protocol 1


ttt duration with Riba.

ttt duration without Riba.

eGFR

On conservative ttt or dialysis Transplanted Kidney

< 30 ml/min/1.73 m2

No cirrhosis Compensate Decompensate No cirrhosis Compensate Decompensate

Selected protocol


ttt duration with Riba.

ttt duration without

Riba.

Querevo + Ribavirin200mg daily -200mg thrice/week-4h before dialysis

Daklinza 60 mg + Sovaldi 400mg + Ribavirin 200mg daily - 200mg thrice/week

Olysio 150mg + sovaldi 200mg

12 weeks 12 weeks

12 weeks 12 weeks24 weeks 24 weeks


Important Consideration

• eGFR by MDRD equation .



•Compensated cirrhosis …. >F3 by fibroscan or equivalent chemical model.

•Decompensate cirrhosis ….. child paugh score class B-7 or higher.

•Ribavirin dose …. withdrawal if not tolerated or Hb level drops by 2 gm/dl despite ESA.


• HBV co-infection

Patients should be treated with the sameprotocols as HCV mono-infected patients. IfHBV replicates at a significant rate,concurrent HBV nucleoside/nucleotideanalogue therapy is indicated.


• HIV co-infection

Patients co-infected with HCV and HIV have higherHCVRNA levels, higher rate of HCV persistence andfaster progression to cirrhosis and end stage liverdisease. The same IFN-free HCV treatmentrecommendations for HIV/HCV co-infected personsas for those with HCV-only infection.


• Drug drug interaction :

Don’t forget to modify doses of cyclosporin, tacrolimus, sirolimus & everlimus according to blood level in transplanted patients.

The interaction in between sofosbuvir and amiodaronewas the earliest life threatening complication, hallmarked by bradycardia and cardiac arrest.

Querevo protocol … restricted to transplanted patient. So, used only by transplant expert.


Risk of treatment



Failed treatment

Re-treatment of patients that do not achieve a SVR orrecur after treatment. The choice of retreatmentprotocol depends on the failed initial protocol asfollows:

- Those with failed Interferon + Ribavirin protocol should be treated according to the same recommendations for treatment-naive patients.


- Olysio based Protocol for failure with any of Harvonibased Protocol or Daklinza based protocol.

- Harvoni based Protocol or Daklinza based protocol forfailure with any Olysio based Protocol .

- Harvoni based Protocol or Daklinza based protocol orOlysio base for failure with any Qurevo basedProtocol .


Adjunctive therapy


RPGN Sever Neuropathywidespread cutaneous

vasculitis with ulceration

Sever active disease

Performed cryoglobulin B cell production Tissue injury

Anti viral

Plasma exchange Rituximab Steroid


Before or After Transplantation


While pre-transplant HCV eradication was highlydesirable in the interferon era, owing to the risk ofgraft loss if the dug was administered aftertransplantation, this policy became questionablewith the availability of safe DAAs. This providesconsiderable relief if transplantation becomes anurgent necessity, including that from deceaseddonors. However, when it can wait, we stronglyrecommend treating patients on the waiting list toavoid the HCV-associated many-fold increased risk ofthrombotic microangiopathy and acute transplantglomerulopathy in the early post-transplant period.



Date post:	25-Jan-2017
Category:	Education
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