bgffd

1. HBV and Immunosuppressive
therapy
Dr Khizar Abbas
Dr Osama Hassan

3. Our concerns
• Anti-HBc positivity siginifies previous exposure to virus .There is
persistence of highly stable cccDNA in liver which can lead to virus
reactivation.
• HBsAg positivity signifies chronic infection with very high risk of
reactivation.

4. Risk Factors
Risk of reactivation depends upon
1. HBsAg positivity status (pts. not candidate of HBV treatment).
2. Type of immunosuppressive therapy.

5. Our Approach
• Screen for HBV in every pt. prior to initiation of IS therapy and
prednisolone > 20mg for > 4 weeks.
• Screening should be done by
1. HBsAg
2. Anti-HBc
3. HBV DNA ( in anti-HBc positive pts.)

6. HBsAg +ve
Refer to specialist for selecting candidates to be treated.
Anti HBc +ve
These pts. need to be stratified for risk of reactivation of HBV.

7. Classification
According to AASLD recommendations pts. are classified into following
groups.
1. very high risk (>20 percent)
2. high risk (10-20 percent)
3. moderate risk (1-10 percent)
4. low risk (<1 percent)
5. very low risk

8. Rituximab
HBsAg +ve HBsAg -ve
very high risk moderate risk

9. Corticosteroids (>20mg for >4weeks )
HBsAg +ve HBsAg -ve
high risk low risk

10. TNF alpha-inhibitors:
HBsAg +ve HBsAg -ve
moderate risk very low risk

11. DMARDS
HBsAg +ve HBsAg -ve
low risk very low risk

12. Low & very low risk
Prophylactic therapy is not recommended.
Frequent monitoring is recommended every 3 months for viral
reactivation by measuring:
1. DNA titers
2. HBs-Ag
3. LFTs

13. Identification of reactivation:
1. A detectable DNA previously undetectable.
2. 10 to 100 folds increase in HBV DNA.
3. Reappearance of HBsAg in previously negative pts.
For pts with evidance of reactivation, antiviral therapy should be
started as soon as possible.

14. Moderate to very high risk
These pts. are candidates of receiving prophylactic antiviral therapy
Preferred agents: entecavir (0.5mg/day)
tenofovir (300mg/day)
Initiation: should be started before I.S therapy especially if hbv dna > 2000
IU/ml.
If <2000 or undetectable, start concurrently with I.S therapy.
Duration: Generally, therapy should be continued for 6 months after I.S therapy
cessation.
For rituximab, antiviral therapy should be continued for 12 to 18 months after
cessation of therapy. And HBV serology should be followed for another 12
months.

15. Vaccination
• Before starting I.S, every patient without evidence of HBV infection
should be vaccinated.
• Ideally vaccination should be done before initiation of therapy as
vaccine may not be effective in immunosuppresed patients.

16. Scenario 1
• A 35-year-old female was diagnosed with rheumatoid arthritis and
was put on Methotrexate requiring screening for HBV exposure. The
patient was positive for Anti-HBc and negative for HBsAg & HBV DNA.
LFTs were normal.
What is risk of virus reactivation in this patient?
• Her RA was not controlled and she was to be transtioned to
Rituximab.Repeat serology yeilded same results.
What is risk of viral reactivation now?

17. Scenario 2
Pt. is recently dignosed with IBD. He is known case of chronic HBV
infection. HBV serology revealed HBsAg positive, Anti-HBc positive and
HBV DNA undetectable. After specialist review, pt. was labelled not a
candidate for treatment.
Sulfasalazine therapy was started.
What is risk of reactivation of virus in this pt.?
Due to progression of her disease, it was decided to start adalimumab.
How should she be re-evaluated and managed?