Dr Kuleesha Kodisinghe

Renal manifestations of HBV infection

HBV infection in CKD patients
Renal transplantation in HBV infection

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

Several types of glomerulonephritis have

been associated with HBV:

MGN - most common type

MCGN
MPGN
FSGS
IgA nephropathy
PAN

These may present as nephritic syndrome or

nephrotic syndrome

Renal disease in children usually has a benign

course with spontaneous remission
The course in adults is not as favourable with
progression to chronic renal insufficiency
occurring in one third

Antiviral agents
Immunosuppression
Plasma exchange

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 renal
disease
Others can be treated with NAs
Dosing of IFN or NAs should be adjusted to
the degree of kidney function

Immunosuppression and plasma exchange

Should be added to antiviral therapy in patients
with rapidly progressive glomerulonephritis and
PAN
Immunosuppression with short course of
corticosteroids +/- cyclophosphamide or
rituximab
In case of immunosuppressive administration, all
HBsAg-positive patients who do not fulfill HBV
treatment indications, should receive preemptive
NA therapy. Preemptive therapy must ideally start
2 weeks before and continue during and for at
least 12 months after the completion of
immunosuppressive therapy

The prevalence of HBV infection among

patients on maintenance haemodialysis in the
developed world is currently low (0-10%) but
remains 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

Clinical implications
Acute HBV infection often mild or
asymptomatic
Majority become chronically infected once
exposed to HBV
Liver disease progresses with modest hepatic
inflammation and prominent fibrosis
Rarely, a fatal condition called fibrosing
cholestatic hepatitis can occur

Special factors to consider in patients

undergoing 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 as
cardiovascular disease, diabetes mellitus and
anemia

Indications for antiviral therapy:

Similar to those in non-CKD HBV patients
All HBsAg-positive candidates for solid-organ
transplantation to maintain undetectable HBV
DNA by the time of transplantation

Choice of antiviral agent:

PEG-IFN can be used but use is limited by the
lower efficacy and frequent side effects,
compared to patients with normal renal
functions
Lamivudine has the longest historical record
for treatment in renal patients but has high
degree of resistance

Nephrotoxic potential seem to be higher for

nucleotide analogues adefovir and tenofovir,
particularly adefovir
Entecavir is the most promising agent for NAnaive patients with CKD, in view of its good
resistance profile and the lesser degree of
nephrotoxicity compared to nucleotide analogues
As long-term entecavir therapy is not so effective
in patients with lamivudine resistance, tenofovir
may be required in such cases

Dose adjustment is needed for all antiviral

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

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 monthly
during the first year and 6 monthly thereafter
In patients at high renal risk - monthly during
the first 3 months, 3 monthly until the end of
the first year and 6 monthly thereafter

Compared with renal transplant recipients

without HBV infection, renal transplantation in
HBV infected patients may result in:
Shorter graft survival
More frequent and more rapid progression of
liver disease to cirrhosis and HCC
Possibility of fulminant hepatitis due to
variations in immune status which occur at
the time of induction or reduction of
immunosuppression during the first months
after transplantation

Type of transplantation
HBsAg-positive patients can be candidates
for solitary renal transplantation only if they
do not have cirrhosis
HBsAg-positive patients with cirrhosis require
simultaneous liver and kidney transplantation
Liver biopsy may be required for CKD patients
with HBV infection to assess the degree of
liver damage

Pre-emptive antiviral therapy

All HBsAg positive patients should be given
pre-emptive therapy
The optimal timing for treatment initiation is
often individualized
Treatment should be continued for the
duration of immunosuppression (lifelong)

NA with high genetic barrier (entecavir or

tenofovir) is currently recommended.
Entecavir is often considered preferable
because of the theoretical lower risk of
nephrotoxicity compared with tenofovir
IFN- therapy is contraindicated in transplant
recipients owing to the increased risk of
acute rejection and low antiviral potency

Patients who are HBsAg-negative but positive

for anti-HBc antibodies should be tested for
HBV 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 of
ALT and HBV DNA testing, and treated with NA
therapy upon virological reactivation (before
biochemical reactivation occurs). If close monitoring
of HBV DNA is not guaranteed, they may also be
treated similarly

Salvage NA therapy in post-renal

transplantation HBV exacerbation
This is a less effective compared with
preemptive NA therapy

Monitoring for liver complications

HBV DNA levels every 36 month
HCC screening with USS - every 3 months in
cirrhotic patients and every 612 months in
non-cirrhotic patients
Evaluation of the impact of hepatitis on the
liver by liver biopsy and non-invasive tests of
fibrosis every 3-5 years

Several types of glomerulonephritis have

been associated with HBV which may present
as nephritic syndrome or nephrotic syndrome
Treatment is mainly based on antiviral agents
Immunosuppression and plasma exchange
should be added on in patients with rapidly
progressive glomerulonephritis and PAN

In CKD patients with HBV, indications for

antiviral therapy are similar to non-CKD HBV
patients
All HBsAg-positive candidates for solid-organ
transplantation should receive antiviral
therapy to maintain undetectable HBV DNA by
the 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

HBsAg-positive patients can be candidates

for solitary renal transplantation only if they
do not have cirrhosis
HBsAg-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

Chrysoula L. Pipili, George V. Papatheodoridis,

Evangelos C. Cholongitas. Treatment of hepatitis B in
patients with chronic kidney disease. Kidney
International. 2013;84:880885
Elias C Chacko, Soondal Koomar Surrun, T P
Mubarack Sani, Joseph M Pappachan. Chronic viral
hepatitis and chronic kidney disease. Postgraduate
Medical Journal. 2010;86:486-492
Anais Vallet-Pichard, Hlne Fontaine, Vincent Mallet,
Stanislas Pol. Viral hepatitis in solid organ
transplantation other than liver. Journal of
Hepatology 2011;55:474482
Patrice Cacoub, Benjamin Terrier. Hepatitis B-Related
Autoimmune Manifestations. Rheumatic Disease
Clinics of North America. 2009;35:125137
AASLD and EASL guidelines on Hepatitis B

THANK YOU