Hepatitis B virus treatment beyond the guidelines: special populations and consideration of treatment withdrawal

Area of Science:

• Hepatology
• Virology
• Internal Medicine

Background:

• Chronic hepatitis B (CHB) is a major cause of liver cirrhosis and hepatocellular carcinoma, leading to over a million deaths annually.
• Effective CHB treatment aims to prevent disease progression by achieving sustained reduction of hepatitis B virus (HBV) DNA to undetectable levels, promoting liver fibrosis regression and potentially reversing cirrhosis.
• Long-term therapy is often necessary, even after HBsAg loss, for patients with advanced liver disease or those unable to maintain off-treatment virological suppression.

Purpose of the Study:

• To clarify current clinical practice guidelines for managing chronic hepatitis B (CHB).
• To define optimal treatment strategies, patient selection criteria, and criteria for discontinuing antiviral therapy for CHB.
• To provide evidence-based recommendations for the use of interferon and nucleos(t)ide analogues in CHB management.

Main Methods:

• Review of recently updated European Association of the Study of the Liver (EASL) clinical practical guidelines for HBV.
• Analysis of treatment recommendations for first-line monotherapies, including interferon, entecavir, and tenofovir disoproxil fumarate.
• Evaluation of criteria for initiating and discontinuing antiviral therapies based on patient HBeAg status, viral load, liver disease severity, and serological markers.

Main Results:

• EASL guidelines recommend interferon or potent oral nucleos(t)ide analogues (entecavir, tenofovir disoproxil fumarate) as first-line CHB monotherapies.
• Treatment is indicated for CHB patients with significant liver disease, those on immunosuppressive therapy, HBV/HIV coinfections, and HBsAg(+) mothers with high viral load to prevent vertical transmission.
• Discontinuation criteria for nucleos(t)ide analogues are clearer for anti-HBe seroconversion, HBsAg loss, or anti-HBs seroconversion with undetectable HBV DNA, though sustained undetectable DNA in anti-HBe(+) patients without significant fibrosis is also considered.

Conclusions:

• Updated EASL guidelines provide clear recommendations on how, who, and when to treat CHB.
• While pegylated interferon treatment cessation is straightforward, decisions for nucleos(t)ide analogues require careful consideration of virological and serological markers.
• Achieving sustained virological suppression is key to preventing CHB progression and improving patient survival.