Can we Stop Nucleos(t)ide Analogs in HBV Chronic Hepatitis?

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.