The main endpoint of hepatitis B treatment is HBV DNA
suppression, which is readily achievable with nucleoside/nucleotide analogues.
HBeAg loss and seroconversion may reflect partial immune control, and HBsAg
loss is the optimal endpoint – often regarded as a functional cure – but both
seldom occur with current therapies.
The guidelines recommend treatment for everyone with
HBV DNA above 2000 IU/ml, elevated ALT, and at least moderate liver
necroinflammation or fibrosis. In addition, people with cirrhosis should start
treatment regardless of viral load (if detectable) or ALT level, while those
with high HBV DNA (>200,000 IU/ml) and elevated ALT should start regardless
of fibrosis stage.
The guidelines state that the treatment of choice is a
potent nucleoside/nucleotide analogue with a high barrier to resistance. These
include entecavir (Baraclude),
tenofovir disoproxil fumarate (TDF or Viread)
and tenofovir alafenamide (TAF or Vemlidy).
TAF has been added to recommended treatment due to its
good efficacy and improved bone and kidney safety compared to TDF.
panel member Maria Buti from Vall d'Hebron
University Hospital in
that TAF “clearly represents an advantage” for people who may be at risk for
bone or kidney problems, including those with altered kidney function, older
people, and those with comorbidities.
of waiting for patients to get renal disease or bone disease, we should be more
pre-emptive in trying to minimise these comorbidities,” argued Kosh Agarwal of
King’s College Hospital in London. “We should be thinking about the prevention of comorbidities for what
is still a long-term therapy for a majority of patients.”
other nucleoside analogues – lamivudine (Epivir),
adefovir (HepSera) and telbivudine (Sebivo or Tyzeka) – are coming off the list of recommended options, as they
are not as potent and are more prone to resistance.
therapy with nucleoside/nucleotide analogues and pegylated interferon is generally
not recommended, according to the guidelines.
remains some controversy about when to discontinue nucleoside/nucleotide
analogue therapy. This should be done after confirmed HBsAg loss, but this
outcome is rare. Discontinuation in patients without cirrhosis who have
achieved HBeAg seroconversion and those with long-term HBV DNA suppression is
left to the discretion of providers.