8/10/2019 HBV Renal Disease
1/29
Dr Kuleesha Kodisinghe
8/10/2019 HBV Renal Disease
2/29
Renal manifestations of HBV infection HBV infection in CKD patients
Renal transplantation in HBV infection
8/10/2019 HBV Renal Disease
3/29
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
8/10/2019 HBV Renal Disease
4/29
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
8/10/2019 HBV Renal Disease
5/29
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
8/10/2019 HBV Renal Disease
6/29
Antiviral agents Immunosuppression
Plasma exchange
8/10/2019 HBV Renal Disease
7/29
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
8/10/2019 HBV Renal Disease
8/29
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
8/10/2019 HBV Renal Disease
9/29
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
8/10/2019 HBV Renal Disease
10/29
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
8/10/2019 HBV Renal Disease
11/29
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
8/10/2019 HBV Renal Disease
12/29
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
8/10/2019 HBV Renal Disease
13/29
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
8/10/2019 HBV Renal Disease
14/29
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
8/10/2019 HBV Renal Disease
15/29
Dose adjustment is needed for all antiviralagents:
Pegylated interferon -2a - 180 g/week ifeGFR 50; 135 g/week if eGFR 3049
8/10/2019 HBV Renal Disease
16/29
8/10/2019 HBV Renal Disease
17/29
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
8/10/2019 HBV Renal Disease
18/29
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
8/10/2019 HBV Renal Disease
19/29
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
8/10/2019 HBV Renal Disease
20/29
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)
8/10/2019 HBV Renal Disease
21/29
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
8/10/2019 HBV Renal Disease
22/29
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
8/10/2019 HBV Renal Disease
23/29
Salvage NA therapy in post-renaltransplantation HBV exacerbation
This is a less effective compared withpreemptive NA therapy
8/10/2019 HBV Renal Disease
24/29
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
8/10/2019 HBV Renal Disease
25/29
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
8/10/2019 HBV Renal Disease
26/29
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
8/10/2019 HBV Renal Disease
27/29
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
8/10/2019 HBV Renal Disease
28/29
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
8/10/2019 HBV Renal Disease
29/29
THANK YOU