D.
Lorne
Tyrrell
Faculty
of
Medicine
and
Dentistry
University
of
Alberta
Edmonton,
Alberta,
Canada
Hepatitis
B
virus
(HBV)
infects
approximately
300
to
350
million
people
worldwide.
Chronic
infection
with
HBV
can
lead
to
cirrhosis
and
hepatocellular
carcinoma.
Lamivudine
is
the
first
oral
medication
that
is
well
absorbed,
well
tolerated,
and
effectively
suppresses
HBV-DNA
levels.
The
goals
of
therapy
with
an
antiviral
agent
include
eliminating
the
virus
and
decreasing
the
rate
of
disease
progression.
Lamivudine
has
been
shown
to
very
effectively
suppress
HBV
replication
in
numerous
clinical
trials.
The
suppression
of
HBV
has
been
correlated
with
significantly
improved
histological
responses,
increased
normalization
of
serum
alanine
aminotransferase,
and
decreased
likelihood
of
hepatitic
fibrosis.
In
addition,
patients
receiving
lamivudine
are
more
likely
to
lose
HBeAg
and
develop
HBsAb.
Seroconversion
of
HBeAg
to
HBeAb,
when
it
is
achieved,
is
likely
to
persist
and
is
often
accompanied
by
long-term
loss
of
serum
HBV-DNA.
The
treatment
of
chronic
HBV
infection
with
lamivudine
is
associated
with
a
significant
risk
of
developing
lamivudine-resistant
HBV
mutants.
This
occurs
in
approximately
15
to
35
per
cent
of
patients
on
lamivudine
for
one
year.
Patients
with
lamivudine-resistant
virus
usually
have
lower
levels
of
HBV-DNA
and
lower
levels
of
alanine
aminotransferase
compared
to
pretreatment
levels.
This
reflects
the
fact
that
YMDD
mutants
are
often
less
replication
competent
than
wild
virus.
The
long-term
benefit
of
continuing
therapy
in
patients
developing
lamivudine-resistant
virus
remains
unclear.
With
the
availability
of
an
effective
and
safe
oral
antiviral
for
HBV
infection,
selection
of
the
appropriate
patients
for
therapy
is
important.
Patients
that
are
HBsAg
positive,
HBeAg
positive,
HBV-DNA
positive
and
have
elevated
serum
alanine
aminotransferase
levels
are
the
best
candidates.
In
these
patients,
therapy
can
be
continued
until
HBeAg
seroconversion
occurs
or
lamivudine
resistant
virus
develops.
Patients
with
HBsAg,
HBeAg,
HBV-DNA
but
normal
serum
alanine
aminotransferase
levels
will
show
a
response
by
decreased
levels
of
HBV-DNA
but
are
less
likely
to
show
HBeAg
seroconversion
or
sustained
response
to
lamivudine.
More
studies
are
required
in
these
patients.
Precore
mutant
patients
will
show
a
virological
and
serum
alanine
aminotransferase
response;
however,
the
endpoint
monitoring
of
therapy
is
more
difficult
without
HBeAg
seroconversion
to
monitor.
Interferon
has
been
reported
to
be
more
effective
in
western
populations
than
in
Asian
populations.
In
contrast,
the
response
to
lamivudine
is
similar
in
Western
and
Asian
populations.
In
summary,
lamivudine
is
a
very
useful
addition
to
the
therapy
of
chronic
HBV
infection.
It
has
several
advantages
over
interferon
for
therapy
of
chronic
HBV
infections,
including
fewer
side
effects,
less
expensive,
and
easier
to
administer
than
interferon.
However,
the
development
of
resistant-mutants
with
lamivudine
is
common.
This
is
not
surprising
as
monotherapy
of
chronic
viral
illnesses
is
frequently
accompanied
by
antiviral
resistance.
Combination
chemotherapy
may
overcome
this
problem.