Complexities in the Management of Hepatitis B in Children
Chronic hepatitis
B virus (HBV) infection by definition is
persistence of hepatitis
B surface antigen (HBsAg) in the serum for
>/=6 months. The risk of developing chronic
HBV infection ranges from 90% in neonates
to <5% in immunocompetent adults.
HBV
acquired by perinatal
infection has a prolonged immune-tolerant
phase, characterized by the presence of hepatitis
Be antigen (HBeAg), high HBV-DNA
and normal alanine aminotransferase (ALT)
levels.
Efficient
and multi-specific helper and cytotoxic T-cell response
is essential for controlling HBV infection. Chronic HBV
infection is characterized by a state of HBV-specific T-cell
hyporesponsiveness.
The
goal of therapy in chronic HBV infection is to eliminate
or significantly suppress HBV replication and prevent the
progression of liver disease to cirrhosis
with the potential development of liver failure or hepatocellular
carcinoma (HCC).
In
adults, drugs currently licensed for treatment of HBV infection:
are standard
and peginterferon-alfa (IFN-alfa), lamivudine
(LMV), adefovir
dipivoxil (ADV), [and entecavir
(Baraclude)]. The first two are also licensed
to use in children.
IFN-alfa
has the advantage of having a more durable response, fixed
duration of treatment and lack of resistant mutants. The
disadvantages of IFN-alfa include need for thrice-weekly
injections, higher cost and more side-effects compared with
the nucleoside analogues.
Nucleoside
analogues can be given orally and used in decompensated
cirrhosis and transplant recipients. ADV and tenofovir can
successfully treat mutants produced after prolonged LMV
therapy.
Current
protocols exclude children with immunotolerant HBV.
Periodic
screening with liver ultrasound scan and alpfa-fetoprotein
(AFP) in all children with chronic HBV infection is recommended.
Five
to ten percent of all liver
transplants are because of HBV. The severe
shortage of cadaveric donor organs has led to the use of
marginal (including anti-HBc-positive) cadaveric donor livers
in selected transplant candidates with high medical urgency.
In
conclusion, the authors write, “Using hepatitis B immunoglobulin
(HBIG) and nucleoside analogues has made the outcome following
liver transplantation for hepatitis B comparable with, if
not slightly better, than that in patients with other diagnoses.”
“Future
treatments should be based on the restoration of HBV-specific
T-cell responses to levels similar to that seen in subjects
controlling HBV.”
09/28/05
Reference
N
Kerkar and others. Hepatitis B in Children: Complexities
of Management. Pediatric Transplantation 9(5): 685-691.
October 2005.
