Blood, 15 October 2002, Vol. 100, No. 8, pp. 3054-3054
CORRESPONDENCE
To the editor:
Prophylactic lamivudine therapy for hepatitis B patients
undergoing immunosuppressive therapy
We read Shibolet et al's recent article1 with
great interest. In an endemic area for chronic hepatitis B infection,
exacerbation of this virus is indeed a serious cause of morbidity and
mortality in patients undergoing cytotoxic or immunosuppressive
therapy.2 Careful prospective serologic testing has shown
that liver damage due to hepatitis B virus (HBV) exacerbation is a
2-stage process. The initial stage occurs during intense cytotoxic or
immunosuppressive therapy and is characterized by enhanced viral
replication, as reflected by increases in serum levels of HBV DNA,
hepatitis B e antigen (HBeAg), and HBV DNA polymerase, which presumably
results in widespread infection of hepatocytes. The second stage is
related to restoration of immune function following withdrawal of
cytotoxic or immunosuppressive therapy, which causes rapid
immune-mediated destruction of infected hepatocytes. Clinically, this
may lead to hepatitis, hepatic failure, and even
death.2
The data presented by Shibolet et al provided a possible new solution
to the problem: to administer lamivudine in a prophylactic manner for hepatitis B patients treated with chemotherapy. This approach is indeed more logical than deferring treatment with lamivudine until hepatitis due to HBV reactivation has occurred. In
keeping with this, both lamivudine3 and
famciclovir4 have been used to treat hepatitis due to HBV
exacerbation. Despite the use of these antiviral agents, some
patients positive for hepatitis B surface antigen
(HBsAg) still developed hepatic failure and died.3 This is
probably related to the late institution of the nucleoside analogues
when the immune-mediated liver damage has already been established.
Although the data provided by Shibolet is promising, we feel that it is
still inconclusive on the use of prophylactic lamivudine in
HBsAg-positive patients undergoing immunosuppressive therapy. First,
the study is retrospective and the diagnosis of HBV reactivation is
based on serology such as the presence of new anti-HBc (hepatitis B
core) IgM and/or sign of viral replication with a
seroconversion from anti-HBe-positive to HBeAg-positive. But
HBsAg-positive patients could suffer from reactivation even if they
remain HBeAg-negative and previous sequence analysis of the HBV
isolated from these patients had demonstrated the presence of point
mutation in the precore region that inhibited the synthesis of
HBeAg.5 On the other hand, serum IgM antibody to hepatitis
B core antigen (anti-HBc) is not specific enough to diagnose HBV
reactivation in patients with chronic HBV infection.6
Therefore, it would be better to demonstrate the presence of HBV
reactivation by showing an increase of serum HBV DNA by quantitation.
Another shortcoming of the study is the differences in the chemotherapy
regimen that was involved in the control and treatment arm. This could
be of relevance; in particular, the use of steroids could
greatly enhance HBV viral replication by stimulating the HBV
glucocorticoid-responsive element.7 Lastly, HBV virologic
factors, such as prechemotherapy serum HBV DNA, has been shown
to affect postchemotherapy HBV reactivation.8 Hence, we
feel that further prospective controlled studies, with all these
factors taken into consideration, are urgently needed before we can
establish the role of prophylactic use of lamivudine in HBsAg-positive
patients undergoing chemotherapy or immunosuppressive therapy.
George K. K. Lau, Albert Lie, and Raymond Liang
Correspondence: George K. K. Lau, University Department of
Medicine, Queen Mary Hospital,102 Pokfulum Rd, Hong Kong, SAR, China;
e-mail: gkklau{at}netvigator.com
References
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Shibolet O, Ilan Y, Gillis S, Hubert A, Shouval D, Safadi R.
Lamivudine therapy for prevention of immunosuppressive-induced hepatitis B virus reactivation in hepatitis B surface antigen carriers.
Blood.
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2.
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3.
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Lau GK, Leung YH, Fong DY, et al.
High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation.
Blood.
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