Chronic infection with Hepatitis B Virus (HBV) is a public health problem,
since more than 240 million people are infected worldwide. Not all of them require
antiviral treatment, but only those with chronic hepatitis, either HBeAg positive or
HBeAg negative.
Complete cure of HBV infection is impossible due to the persistence of covalently
closed circular DNA (cccDNA) integrated into the hosts’ liver cells. An ideal end-point
is the functional cure: HBsAg loss with or without HBs seroconversion, which is also
rather hard to achieve, especially after nucleos(t)ide analogs (NA) treatment. Thus, the
main endpoint of all current treatment strategies is long-term suppression of HBV
DNA levels. All NA therapies have a potent inhibition effect on HBV replication. The
problem is that after NA cessation the viral replication restarts.
The only firm indication to stop NA therapy is HBsAg loss, preferably with
seroconversion to anti-HBsAb. In HBeAg positive non-cirrhotic patients, NA therapy
can be stopped if HBeAg seroconversion and HBV DNA undetectability are achieved,
but only after 12 months of consolidation therapy. In HBeAg negative chronic
hepatitis, life-long NA long-term treatment is recommended. However, published data
showed that viral relapse following NA cessation in these patients can trigger an
immune response that would lead to a durable remission. In HBeAg-negative patients,
treatment discontinuation can be considered after more than 3 years of on-treatment
undetectable HBV DNA and only if close monitoring is possible.
NA treatment should be continued indefinitely in cirrhotic patients.
Keywords: HBeAg seroconversion, HBsAg loss, Hepatitis B virus, Nucleos(t)ide
analogs, Stop treatment, Virologic response.
