hbv renal disease

8/10/2019 HBV Renal Disease

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Dr Kuleesha Kodisinghe


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Renal manifestations of HBV infection HBV infection in CKD patients

Renal transplantation in HBV infection


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Pathogenesis may be related to: glomerular deposition of immune complexes

direct cytopathic effect of the virus on cells of

the kidney virus induced immunological effector

mechanisms (lymphocytes, antibody)

indirect effects of virus induced cytokines


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Several types of glomerulonephritis havebeen associated with HBV: MGN - most common type

MCGN

MPGN

FSGS

IgA nephropathy

PAN

These may present as nephritic syndrome ornephrotic syndrome


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Renal disease in children usually has a benigncourse with spontaneous remission

The course in adults is not as favourable withprogression to chronic renal insufficiencyoccurring in one third


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Antiviral agents Immunosuppression

Plasma exchange


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Antiviral agents Treatment is mainly based on antiviral agents

Treatment is similar to standard clinical

practice guidelines for HBV infection PEG-IFN is the preferable treatment option

for young patients with HBV-associated renaldisease

Others can be treated with NAs Dosing of IFN or NAs should be adjusted to

the degree of kidney function


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Immunosuppression and plasma exchange Should be added to antiviral therapy in patients

with rapidly progressive glomerulonephritis andPAN

Immunosuppression with short course of

corticosteroids +/- cyclophosphamide orrituximab

In case of immunosuppressive administration, allHBsAg-positive patients who do not fulfill HBVtreatment indications, should receive preemptive

NA therapy. Preemptive therapy must ideally start2 weeks before and continue during and for atleast 12 months after the completion ofimmunosuppressive therapy


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The prevalence of HBV infection amongpatients on maintenance haemodialysis in thedeveloped world is currently low (0-10%) butremains higher (2-20%) in developing

countries

Transmission may occur from: Blood transfusions

Nosocomial contamination Transplantation of an infected renal graft from an

HBsAg-positive or anti-HBc positive donor


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Clinical implications Acute HBV infection often mild or

asymptomatic

Majority become chronically infected onceexposed to HBV

Liver disease progresses with modest hepaticinflammation and prominent fibrosis

Rarely, a fatal condition called fibrosingcholestatic hepatitis can occur


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Special factors to consider in patientsundergoing hemodialysis: often have no or moderate elevations of

serum aminotransferases owing to altered

inflammatory response often have lower serum HBV DNA levels due

to removal by hemodialysis higher risk of occult HBV infection

associated comorbidities such ascardiovascular disease, diabetes mellitus andanemia


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Indications for antiviral therapy: Similar to those in non-CKD HBV patients

All HBsAg-positive candidates for solid-organtransplantation to maintain undetectable HBVDNA by the time of transplantation


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Choice of antiviral agent:

PEG-IFN can be used but use is limited by thelower efficacy and frequent side effects,

compared to patients with normal renalfunctions

Lamivudine has the longest historical recordfor treatment in renal patients but has high

degree of resistance


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Nephrotoxic potential seem to be higher fornucleotide analogues adefovir and tenofovir,particularly adefovir

Entecavir is the most promising agent for NA-

naive patients with CKD, in view of its goodresistance profile and the lesser degree ofnephrotoxicity compared to nucleotide analogues

As long-term entecavir therapy is not so effective

in patients with lamivudine resistance, tenofovirmay be required in such cases


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Dose adjustment is needed for all antiviralagents:

Pegylated interferon -2a - 180 g/week ifeGFR 50; 135 g/week if eGFR 3049


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Regular eGFR monitoring should be performed: Nucleoside analogues - in patients at high

renal risk

Nucleotide analogues in all patients

In patients at low renal risk - 3 monthlyduring the first year and 6 monthly thereafter

In patients at high renal risk - monthly during

the first 3 months, 3 monthly until the end ofthe first year and 6 monthly thereafter


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Compared with renal transplant recipientswithout HBV infection, renal transplantation inHBV infected patients may result in: Shorter graft survival

More frequent and more rapid progression ofliver disease to cirrhosis and HCC

Possibility of fulminant hepatitis due tovariations in immune status which occur at

the time of induction or reduction ofimmunosuppression during the first monthsafter transplantation


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Type of transplantation HBsAg-positive patients can be candidates

for solitary renal transplantation only if theydo not have cirrhosis

HBsAg-positive patients with cirrhosis requiresimultaneous liver and kidney transplantation

Liver biopsy may be required for CKD patients

with HBV infection to assess the degree ofliver damage


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Pre-emptive antiviral therapy

All HBsAg positive patients should be givenpre-emptive therapy

The optimal timing for treatment initiation isoften individualized

Treatment should be continued for theduration of immunosuppression (lifelong)


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NA with high genetic barrier (entecavir ortenofovir) is currently recommended.Entecavir is often considered preferablebecause of the theoretical lower risk of

nephrotoxicity compared with tenofovir IFN- therapy is contraindicated in transplant

recipients owing to the increased risk ofacute rejection and low antiviral potency


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Patients who are HBsAg-negative but positivefor anti-HBc antibodies should be tested forHBV DNA Those with detectable HBV DNA should be treated

similarly to HBsAg positive patients Those with undetectable HBV DNA should be

followed up carefully (1-3 monthly) by means ofALT and HBV DNA testing, and treated with NAtherapy upon virological reactivation (before

biochemical reactivation occurs). If close monitoringof HBV DNA is not guaranteed, they may also betreated similarly


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Salvage NA therapy in post-renaltransplantation HBV exacerbation

This is a less effective compared withpreemptive NA therapy


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Monitoring for liver complications HBV DNA levels every 36 month

HCC screening with USS - every 3 months incirrhotic patients and every 612 months innon-cirrhotic patients

Evaluation of the impact of hepatitis on theliver by liver biopsy and non-invasive tests of

fibrosis every 3-5 years


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Several types of glomerulonephritis havebeen associated with HBV which may presentas nephritic syndrome or nephrotic syndrome

Treatment is mainly based on antiviral agents

Immunosuppression and plasma exchangeshould be added on in patients with rapidlyprogressive glomerulonephritis and PAN


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In CKD patients with HBV, indications forantiviral therapy are similar to non-CKD HBVpatients

All HBsAg-positive candidates for solid-organ

transplantation should receive antiviraltherapy to maintain undetectable HBV DNA bythe time of transplantation

Entecavir is the most promising agent for

NA-naive patients with CKD Dose adjustment and regular eGFR

monitoring is needed for all antiviral agents


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HBsAg-positive patients can be candidatesfor solitary renal transplantation only if theydo not have cirrhosisHBsAg-positive patients with cirrhosis require

simultaneous liver and kidney transplantation All HBsAg positive patients should be given

pre-emptive antiviral therapy NA with high genetic barrier (entecavir or

tenofovir) is recommended Regular monitoring for liver complications is

needed after transplantation


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Chrysoula L. Pipili, George V. Papatheodoridis,Evangelos C. Cholongitas. Treatment of hepatitis B inpatients with chronic kidney disease. KidneyInternational. 2013;84:880885

Elias C Chacko, Soondal Koomar Surrun, T P

Mubarack Sani, Joseph M Pappachan. Chronic viralhepatitis and chronic kidney disease. PostgraduateMedical Journal. 2010;86:486-492

Anais Vallet-Pichard, Hlne Fontaine, Vincent Mallet,Stanislas Pol. Viral hepatitis in solid organtransplantation other than liver. Journal ofHepatology 2011;55:474482

Patrice Cacoub, Benjamin Terrier. Hepatitis B-RelatedAutoimmune Manifestations. Rheumatic DiseaseClinics of North America. 2009;35:125137

AASLD and EASL guidelines on Hepatitis B


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hbv renal disease

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