proportion of people receiving oral antiviral treatment for hepatitis B virus
(HBV) may be able to achieve durable virological remission after the withdrawal
of therapy, investigators report in Hepatology.
Researchers conducted a systematic review of studies examining rates and
predictors of virological control after the withdrawal of oral antiviral
therapy for chronic HBV infection. Overall, 51% were in virological remission
twelve months after discontinuation of therapy, with hepatitis B e antigen
(HBeAg)-positive people more likely to achieve this outcome than HBeAg-negative people. Longer duration of therapy was associated with increased chances of
virological remission for HBeAg-negative people.
overall rate of durable VR [virological remission] was approximately 46%, with
most of the relapses occurring within the first or second year after NA [nucleoside/nucleotide
analogue] discontinuation,” comment the authors. “Additional studies are
required to identify predictors of durable VR.”
therapy can have major health benefits for people with chronic HBV. However,
it is currently unclear if virological control of HBV can be maintained after
the withdrawal of this treatment.
Partial recovery from an illness, an alternative word for regression.
team of investigators therefore conducted a meta-analysis and systematic review
of virological and biomedical outcomes in people with chronic HBV who discontinued
oral nucleoside/nucleotide therapy. Participants were required to have received at least
twelve months of treatment and to have been followed for a minimum of twelve
months after stopping treatment. Viral control was defined as HBV levels
below 20,000 IU/ml.
identified 25 studies conducted between 2002 and 2014; all but one were cohort
studies, the remaining study being a randomised control trial. One study was
evaluated as high quality, 14 as acceptable and ten as low quality. A total of
1726 people discontinued oral antiviral therapy and post-therapy follow-up
data were available for 1716 of these individuals. Of these, 43% were
HBeAg-positive and 56% were HBeAg-negative – HBeAg status was unclear in the
remaining 1% of participants. Cirrhosis was present in 18% of participants with
reported histological data at the time treatment was stopped.
virological remission was reported in 46% of participants. The rate was higher in people who were HBeAg-positive than in people who were HBeAg-negative (50 vs
38%, p < 0.001).
Overall rates of remission
at 6, 12, 24 and 36 months were 68, 51, 39 and 38%, respectively.
Rates of remission at all follow-up points were higher among HbeAg-positive
people than HBeAg-negative people.
remission – good liver function – was observed in 65% of participants overall. The
rate was higher – but not statistically so – among HBeAg-positive people
compared to HBeAg-negative people (76 vs 57%).
HBsAg loss was
observed in 2% of patients, with no difference in the rate of this outcome
between initially HBeAg-positive and HBeAg-negative people (1 vs 1.7%).
therapy was not associated with virological remission rates overall. However, for
HBeAg-negative people, the twelve-month remission rate was 35% for people
who received less than 24 months of treatment, compared to a remission rate of
75% for people who received over 24 months of oral antiviral treatment.
with virological remission in individual studies included lower baseline ALT,
lower baseline HBV DNA, younger age, female gender and absence of cirrhosis.
The researchers call for more studies to identify factors associated with
A deterioration in
liver function post-treatment discontinuation was reported in 39% of patients
with cirrhosis. Liver decompensation occurred in 1% of patients and 2.5%
developed jaundice. Retreatment was effective in all but one person who died
because of liver failure.
of long-term NA therapy may be attempted if close follow-up can be guaranteed
in patients without advanced liver disease,” conclude the authors. “NA
discontinuation may be considered not only in HBeAg-positive patients without
cirrhosis who achieve stable HBeAg seroconversion for at least 12 months but
also in HBeAg-negative patients without cirrhosis who remain in biological
remission and virological remission under NAs for a few years.”