Controversies in treatment of chronic hepatitis B

Although oral antiviral agents can provide an effective viral suppression to reduce risk of HCC and improve patient survival, there are still a few controversies in the treatment of chronic hepatitis B nowadays

Immune tolerance patients - treat or observe?
Patients with immune tolerance have high HBV DNA, which has been shown to associate with higher HCC risk. There are also clinical data suggesting higher HCC risk among immune tolerance patients if left untreated. However, the current antiviral agents are no good enough to treat this difficult-to-treat patient group.

Inactive carriers - do they exist?
Traditionally, negative HBeAg, low HBV DNA and normal ALT are used to define inactive carriers. Patients with advanced liver fibrosis and HCC are still seen among these patients. Nowadays, non-invasive assessment of liver fibrosis and quantitative HBsAg will be required to define a true inactive carrier state.

Stopping NA before HBsAg loss - is it feasible?
Regional guidelines have recommended stopping NA after HBeAg seroconversion in HBeAg-positive patients and undetectable HBV DNA for 2-3 years in HBeAg-negative patients. Significant relapse has been observed after stopping NA according to these criteria. In European patients, HBsAg loss has been seen after post-treatment flare. HBsAg level may be able to select patients with a higher chance of post-treatment remission.

Functional cure - is it needed?
Functional cure as defined by HBsAg loss is the next immediate goal of new anti-HBV agents. Although long-term NA has been shown to associate with reduced HCC risk, there are good data suggesting a further reduced HCC risk among NA users if HBsAg loss is achieved.