BMT UNIT

Prevention and Treatment of Hepatitis for patients undergoing

HSCT

1-Initial investigations for patients and donors: HbsAg, anti

HBsAB, antiHBcAB, HBeAg, antiHBeAB, HCV RNA.
2-For hepatitis B

Any recipient/donor positive for HBsAg will be tested for

anti HDV
Recepient/donor HBsAg negative but HBe Ag positive
have to be tested molecularly for pre-core mutant if
positive they will be excluded either as recipient or
donor
Recepient /donor positive for HBsAg will undergo PCR
for HBV DNA
Recepient/donor HBsAg negative but antiHBcAb
positive and antiHBsAb positive , no further test need to
be done and proceed for transplant ( ie no need for HBV
DNA as subject is considered immune)
Recepient /donor HBsAg negative but antiHBcAB
positive but Anti HBsAB negative test for HBV DNA
In donor if positive for HBV DNA, he will receive
treatment with lamivudine for 4weeks then retested for
HBV DNA if undetectable proceed for stem cell
collection and In the mean time recepient should receive
active immunization with at least 2 doses at 4 weeks
interval if antiHBsAB<10IU/L and to receive HB IG prestem cell infusion and recipient will start lamivudine
100mg OD qd 1 week pre transplant to be continued for
1year after stopping immunosuppressive treatment.
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PS Recepients receiving sc infusion from a positive

donor whether hepatitis B or C , Test harvest product for
HBV DNA or HCV RNA to be recorded in patients file for
future re-assessment.
In recipient with HBsAg negative, antiHBcAB positive ,
antiHBsAB negative like wise check HBV DNA . If
negative proceed with vaccination if positive start
lamivudine therapy. Patient is not acceptable for
transplant unless the virus load< 105
Liver function tests should also be done. Recepient
positive for hepatitis B past infection with liver function
abnormality should undergo liver biopsy pretransplant
checking for fibrosis, cirrhosis and iron load

Table 1: Investigations based on HBV serostatus of recepient

HSCT recipient serostatus
HBsAg negative
antiHBcAB positive
antiHBsAB positive

Investigations
1-repeat profile
2-If antiHBsAB positive
proceed with SCT
3-If anti HBsAB negative check
HBV DNA
- If negative complete
vaccination schedule
- If positive quantify viral
load and proceed with
preeumptive therapy

HBsAg negative
antiHBcAB positive
antiHBsAB negative

check HBV DNA

- If negative complete
vaccination schedule

HBsAg positive

If positive quantify viral load

and proceed with preeumptive
therapy
Check viral load
Proceed with preeumptive
therapy

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Table 2:-Investigations for donor based on HBV serostaus of

donor and recepient:
Donor status
Recipient status
HBsAg negative
HBV naive
antiHBc positive
antiHBsAB negative

HBsAg negative
HBV naive
antiHBSAB positive
antiHBcAb positive

HBsAg negative
HBsAg positive
antiHBsAB positive
antiHBcAb positve

recommendations
Check for HBV DNA
-If negative check at
the time of harvest
Proceed without
intervention if
negative
If positive ttt donor
with lamivudine till
viral load
undetectable and
recipient should
receive preumptive
therapy ie
lamivudine 100mg
start 1wk pre-SCT
If antiHBsAB
positive proceed
without intervention
If antiHBsAB
negative check HBV
DNA and proceed
accordingly
Confirmed profile
Preferred donor
Receipient should
receive lamivudine

-Reduce harvest dose to minimal without compromising

planned CD34 cell dose.

3- HCV:

Management of Donor positive for HCV:

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Interferon 3million unit sc 3 times weekly + ribavirin

1000mg/day for donors<75Kg and 1200mg/d for donors>75Kg
for 1-3months till level is undetectable. Stop treatment 2
weeks before stem cell collection as it affect stem cell
Recepients positive for HCV, patient must undergo liver
biopsy pre-transplant . If patient has evidence of liver
cirrhosis, fibrosis or severe inflammation better to avoid
transplant. Patient should receive IFN + ribavirin till viral
load , 105 as very high viral load increase patient's
mortality and morbidity post transplant. HCV patients
should avoid CTX and high dose TBI, better to use
Fludarabine , low dose TBI

Selection of patients:
1.
2.
3.
4.
5.

Donor/recipient with hepatitis B pre-core mutant are

excluded
Recepients with co-infection ie HBV and HDV or HCV are
excluded
Patients with HCV whose liver biopsy show evidence of
cirrhosis, fibrosis or severe inflammation are excluded
Patients whose liver function show evidence of chronic
liver disease are excluded
Recepient should have viral load <105 before undergoing
transplant

Monitoring of Patients:

Categorise patients for HBV into low and high risk

patients
Low risk patients: HBsAg negative with negative all other
markers or antiHBcAB positive and antiHBsAB positive
with HBV DNA negative
High risk patient: HBsAg positive and or antiHBcAb
positive or HBsAg positive donor

Low risk patient needs no treatment , however if

recipient HBsAg negative but positive antiHBcAB and
antiHBsAB perform frequent HBV DNA assessment
( every 2 weeks) and start treatment if there is a 6 log

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rise in HBV DNA titer or change from negativity to

positivity.
High risk patient should receive preumptive therapy with
lamivudine 100mg PO qd , LFT should be carried weekly
for 6months then every 2weeks until stoppage of all
immunosuppressive therapy, HBV DNA should be done
monthly, immediately if there is threefold rise in liver
enzymes, anytime there is seroconversion, then every
2weeks for 3months after cessation of antiviral therapy.
HCV recipient- If normal or slightly abnormal ALT at
SCT , without any post-HSCT liver diseasenothing
needs to be done

Avoid rapid tapering of immunosuppressives in both

HBV and HCV as this is associated with with hepatitis

reactivation.ie, at day 180 CsA to be tapered 5% every 23weeks depending on liver function and clinical
assessment instead of weekly tapering
Reactivation management:
Definition: 6 log rise in HBV DNA titer or change from
negativity to positivity

On appearance of evidence of reactivation, assess viral

load . Initially rule out all DD; GVHD, drug toxicity, iron
overload, CMV, EBV. Even proceed to liver biopsy

HBV positive reactivation, proceed with lamivudine

therapy if patient was on observation only. If patient was
on preumptive therapy with lamivudine proceed second
line therapy entecavir 1mg POqd, or less effective
adefovir 10mg/day

HCV positive patients : If reactivation occur before 1year

after transplant patient is not to receive antiviral therapy
( IFN+ribavirin) but to receive only for steroid therapy.
For patient with reactivation more than one year after
transplant, test donor chimerism if full donor and patient
does not have low blood count start with IFN+ ribavirin
for 48 weeks( or until patient can tolerate)
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In case of iron overload patient should receive

phlebotomy or chelating agent before proceeding with
IFN

Patients with hepatitis flare( B or C) inspite of treatment

with antiviral therapy with risk of hepatic failure start
prednisolone 2mg/kg for 2weeks then slow tapering) or
60mg for 4days and until PT has stablised then decrease
10mg every 4days till you reach 30mg then daily
reduction of 2-5-5mg every 2weeks

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