When can patients with chronic hepatitis B cease taking their antiviral medication, such as entecavir (Entecavir) or tenofovir (Tenofovir)?

From the Guidelines

Patients with chronic hepatitis B should cease taking antiviral medication after serum HBsAg loss, or in HBeAg-positive patients, at least 12 months after HBV DNA is undetectable and serum HBeAg loss or seroconversion has been achieved. This recommendation is based on the most recent and highest quality study, which provides guidelines for the management of chronic hepatitis B 1. The study suggests that cessation of nucleos(t)ide analog (NA) therapy is recommended after serum HBsAg loss in CHB patients, and in HBeAg-positive CHB patients, cessation of NA therapy could be considered at least 12 months after HBV DNA is undetectable and serum HBeAg loss or seroconversion has been achieved.

Key Considerations

• For HBeAg-positive patients, treatment may be stopped after achieving HBeAg seroconversion plus undetectable HBV DNA for at least 12 months of consolidated therapy.
• For HBeAg-negative patients, treatment discontinuation requires much longer periods of viral suppression, typically at least 3 years of undetectable HBV DNA with regular monitoring.
• Patients with cirrhosis or advanced fibrosis generally require lifelong therapy regardless of serological response due to the high risk of decompensation with viral reactivation.
• The decision to stop treatment should always be individualized and made after careful discussion between the patient and hepatologist, weighing the benefits of medication cessation against the risks of viral reactivation.

Monitoring After Treatment Cessation

• Liver function testing and serum HBV DNA measurement at 1- to 6-month intervals and HBeAg/anti-HBe testing at 3- to 6-month intervals are recommended during the first year after cessation of antiviral treatment 1.
• If virological response is maintained after cessation of NA therapy, follow-up HBsAg/anti-HBs testing should be performed to confirm HBsAg loss, maintenance, or reversion 1.

Comparison with Other Guidelines

• The Korean Association for the Study of the Liver (KASL) guidelines recommend cessation of NA therapy after serum HBsAg loss or HBeAg loss/seroconversion with 12 months consolidation plus undetectable HBV DNA 1.
• The American Association for the Study of Liver Diseases (AASLD) guidelines recommend treatment until HBsAg is lost or HBeAg seroconversion with 12 months consolidation plus undetectable HBV DNA 1.
• The European Association for the Study of the Liver (EASL) guidelines recommend treatment until HBsAg loss with or without anti-HB seroconversion 1.

From the FDA Drug Label

Your hepatitis B virus (HBV) infection may get worse if you stop taking entecavir tablets. This usually happens within 6 months after stopping entecavir tablets. Do not stop entecavir tablets without talking to your healthcare provider Your healthcare provider should monitor your health and do regular blood tests to check your liver if you stop taking entecavir tablets.

The decision to cease taking antiviral medication such as entecavir should be made under the guidance of a healthcare provider. Patients should not stop taking entecavir tablets without consulting their healthcare provider. The provider will monitor the patient's health and perform regular blood tests to check the liver if the medication is stopped 2.

From the Research

Ceasing Antiviral Medication for Chronic Hepatitis B

• The decision to cease taking antiviral medication, such as entecavir or tenofovir, for patients with chronic hepatitis B is complex and depends on various factors, including the patient's clinical features, antiviral efficacy, and risk of developing resistance 3.
• Currently, there is no clear consensus on when to stop antiviral therapy, as the optimal duration of treatment is unknown 4.
• Some studies suggest that a feasible stopping rule with off-therapy monitoring plan has been developed, but the criteria for stopping treatment are not well established 4.
• The goal of antiviral therapy is to prevent cirrhosis and hepatocellular carcinoma by suppressing HBV replication, and treatment should be individualized based on patient characteristics, such as HBV DNA levels, ALT levels, and liver histology 5.
• New therapeutic strategies in clinical development aim to achieve a functional cure, where the HBV envelope protein HBsAg is no longer detectable in the serum, but it is unclear when discontinuation of long-term therapy with entecavir or tenofovir is feasible 6.
• Combination therapy with pegylated interferon-α and nucleoside/nucleotide analogs, such as entecavir or tenofovir, may be an attractive approach for treating chronic HBV infection, but large studies are needed to assess the safety and efficacy of combination therapies to increase the rates of HBsAg seroclearance over the long term 7.

Factors Influencing Treatment Duration

• Patient characteristics, such as HBV DNA levels, ALT levels, and liver histology, play a crucial role in determining treatment duration 5.
• The risk of developing resistance and the long-term safety profile of antiviral medications should also be considered when deciding on treatment duration 3.
• The development of new drugs and new strategies is the highest priority in further improving the outcomes of treatment, and future studies may provide more guidance on when to cease antiviral medication 4.