The presentation describes Hepatitis B infection in Stem cell transplant patients and role of lamivudine prophylaxis in prevention. The presentation was made at annual meeting of Mumbai Hematology Group held at ACTREC, Mumbai in 2014.

1. Hepatitis B Related Serological Events In
Hematopoietic Stem Cell Transplant Patients
and Efficacy Of Lamivudine Prophylaxis
Against Reactivation
Alok Gupta, MD1*, Bhausaheb Bagal, MD, DM.1*, Jayant Gawande, MD,
DM1*, Sachin Punatar, MD1*, Bharat Chauhan, MD1*, Libin Mathew1*, Vivek
Bhat, MD2*, Sadhana Kannan, MSc3* and Navin Khattry, MD, DM.1*
1Bone Marrow Transplant Unit, ACTREC, Tata Memorial Centre, Mumbai,
India; 2Microbiology, ACTREC, Tata Memorial Centre, Mumbai,
India; 3Biostatistics, ACTREC, Tata Memorial Centre, Mumbai, India

2. Hepatitis B Infection
Remote Hepatitis B
Infection (RHBI)

4. Background
• Remote Hepatitis B infection (RHBI) is characterized by the
persistence of Hepatitis B virus (HBV) genome at very low levels of
replication in the hepatocytes and/or peripheral blood
mononuclear cells.
• Prevalence: 4-18 % in non-endemic areas to 55 % in endemic areas.
• HBsAg, HBeAg and HBV DNA in serum are negative while anti-HBs
and/or anti-HBcIgG are positive.
• Reactivation of RHBI is an important cause of morbidity in patients
undergoing hematopoietic cell transplant (HCT).

5. Aim
 To determine the prevalence of RHBI and HBV reactivation,
the role of lamivudine in preventing HBV reactivation and
pattern of change in serological markers at reactivation in
patients undergoing HCT.

6. Definitions
RHBI: Defined as positive anti-HBcIgG and/or anti-HBs
(without history of HBV vaccination) with negative HBsAg
and anti-HBcIgM and normal liver function.
HBV reactivation: Defined as increase in transaminases ≥ 3
times the ULN with HBV DNA and/or anti-HBs and/or anti-
HBcIgG and/or HBsAg positivity (anti-HBcIgM being
negative).

7. Study design
• Retrospective study
• Study Period: March 2010 to May 2013
• Study centre: Bone Marrow Transplant Unit, ACTREC, Tata
Memorial Centre, Mumbai, India
• Patients: 205 patients who underwent HCT (autologous- 103,
allogeneic- 102) were included.

8. Methods
• Virological testing
Pre-transplant: All patients were tested by ELISA for
HBsAg, anti-HBs, anti-HBcIgM and anti-HBcIgG within 1
month prior to transplant.
Post transplant: At the time of deranged liver function,
patients were tested for HBsAg, Anti-HBs, Anti-HBc IgM,
Anti-HBc IgG, Anti-HCV, Anti-HEV and Anti-HAV by ELISA.
HBV DNA and HCV RNA were tested by PCR.
All BMT donors were tested for HBsAg, anti-HBs, anti-
HBcIgM and anti-HBcIgG within 1 month prior to
transplant.

9. Methods
• Patients diagnosed with RHBI were divided into 2 groups
based on the use of lamivudine prophylaxis.
1. Prophylaxis Group: All but one patient with anti-HBcIgG
positivity (irrespective of anti-HBs status).
2. No Prophylaxis Group: Patients with only anti-HBs
positivity.

10. Results

11. RHBI
14% (n=28)
No RHBI 86%
(n=177)
Prevalence of Remote Hepatitis B
Infection (RHBI)
N=205

12. Distribution of patients
Total patients
n=205
Patients with
RHBI
n=28 (14%)
Prophylaxis
group
n=15
Reactivation
rate 0/15 (0%)
No prophylaxis
group
n=13
Reactivation
rate
12/13 (92.30%)
Patients
without RHBI
n=177 (86%)
All in no
prophylaxis
group
Reactivation
rate
9/177 (5.08%)

13. Clinical and virological characteristics of Remote Hepatitis B
Infection and outcome of lamivudine prophylaxis
Characteristic Prophylaxis Group
(n=15)
No-prophylaxis group
(n=13)
Total- RHBI
(n=28)
Median Age in years (range) 34 (10-55) 30 (5-49) 29 (5-55)
Gender M/F 12/3 7/6 19/9
Diagnosis
AML 3 7 10
ALL 1 2 3
CML 0 2 2
Lymphoma 4 1 5
Multiple myeloma 4 0 4
Aplastic anemia 3 1 4
Type of transplant
Autologous 8 1 9
Allogeneic 7 12 19
Pre-transplant HBV serology
HBsAg positive 0 0 0
anti-HBcIgG positive * 14 1 15
anti-HBs positive * 8 11 19
Developed HBV reactivation 0 12 P <0.001
* Pretransplant anti-HBcIgG and anti-HBs not available in one patient in No-prophylaxis group

14. Reactivation
10% (n=21)
No
reactivation
90% (n=184)
Incidence of HBV reactivation
N=205

15. Distribution of patients
Total patients
n=205
Patients with
RHBI
n=28 (14%)
Prophylaxis
group
n=15
Reactivation
rate 0/15 (0%)
No prophylaxis
group
n=13
Reactivation
rate
12/13 (92.30%)
Patients
without RHBI
n=177 (86%)
All in no
prophylaxis
group
Reactivation
rate
9/177 (5.08%)

16. Clinical and virological characteristics of HBV reactivation
Characteristic HBV reactivation
No. of Patients 21/205 (10%)
Median Age in years (range) 30 (5-49)
Gender M/F 12/9
Diagnosis
AML 12
ALL 5
CML 3
Lymphoma 1
Multiple myeloma 0
Aplastic anemia 0
Type of transplant
Autologous 1
Allogeneic 20
Serological profile Pre-transplant At reactivation
HBsAg positive 0 1
anti-HBcIgG positive 1 7
anti-HBs positive 11 7
HBV DNA positive 0 7
All markers negative 9 0

17. anti-HBcIgG *
positive
5% (n=1)
anti-HBs
positive
52% (n=11)
All markers
negative
43% (n=9)
Pre-transplant serological profile of patients
with HBV reactivation (N=21)
*All patients with anti HBcIgG positive received
lamivudine prophylaxis except 1

18. HBsAg positive
4% (n=1)
anti-HBcIgG
positive
32% (n=7)
anti-HBs
positive
32% (n=7)
HBV DNA
positive
32% (n=7)
Post-transplant serological profile of patients
with HBV reactivation (N=21)

19. Changes in serological profile at reactivation (N=21)
Pattern of change No. of patients (%)
Reverse seroconversion (HBsAg negative to
HBsAg positive)
1 (5%)
Loss of antibody 5 (24%)
anti-HBcIgG (positive to negative) 1
anti-HBs (positive to negative) 4
Gain of antibody 8 (39%)
anti-HBcIgG (negative to positive) 7
anti-HBs (negative to positive) 1
HBV viremia 7 (33%)
Patients responded to lamivudine therapy (%) 20 (95)
Median time to response 17 days
Lamivudine therapy at reactivation

20. Pre-transplant Serological profile of patients with
HBV viremia at reactivation (N=21)
Serological profile HBV viremia
(n=7)
No HBV viremia
(n=14)
HBsAg positive 0 0
anti-HBcIgG positive 1 0
anti-HBs positive 0 10 (p=0.023)
All markers negative 5 4

21. Conclusions
1. Incidence of RHBI in patients undergoing HCT is high in our
setting.
2. Lamivudine prophylaxis protects against HBV reactivation post
transplant.
3. We recommend lamivudine prophylaxis not only in patients with
anti-HBcIgG positivity but also in those with isolated anti-HBs
positivity given the high rate of HBV reactivation in these
patients.
4. HBV Serology does not identify all cases of RHBI.
5. Therefore, all serological markers for HBV should be repeated at
the time of deranged liver functions post transplant.

22. Thank You