What is the treatment approach for a patient with chronic hepatitis B (HBV) infection who has achieved HBsAg seroclearance while on antiviral medications such as entecavir (generic name) or tenofovir (generic name)?

Treatment Approach After HBsAg Seroclearance on Antiviral Therapy

Antiviral therapy with entecavir or tenofovir should be discontinued once HBsAg seroclearance is confirmed, as this represents achievement of the ideal treatment endpoint and functional cure of chronic hepatitis B. 1, 2

Rationale for Treatment Discontinuation

HBsAg seroclearance (with or without anti-HBs seroconversion) represents the ultimate goal of chronic hepatitis B therapy across all major international guidelines. 3 This endpoint signifies:

• Functional cure of HBV infection with sustained suppression of viral replication 1
• Reduced risk of disease progression to cirrhosis, hepatocellular carcinoma, and liver-related mortality 3
• Elimination of the need for continued antiviral therapy, even in patients who previously required indefinite treatment 1, 2

The achievement of HBsAg loss occurs infrequently during nucleos(t)ide analogue therapy (approximately 1-5% after many years of treatment), making it a rare but definitive stopping point. 3

Confirmation of HBsAg Seroclearance

Before discontinuing therapy, confirm HBsAg seroclearance by:

• Repeat HBsAg testing on at least two separate occasions, 3-6 months apart, to ensure sustained seroclearance 3
• Document anti-HBs status, though seroconversion to anti-HBs is not required for treatment discontinuation 3, 1
• Verify undetectable HBV DNA by sensitive PCR assay 3, 1

Post-Treatment Monitoring Strategy

After discontinuing antiviral therapy following HBsAg seroclearance, implement the following monitoring schedule:

• HBsAg and ALT testing every 3-6 months for the first year after discontinuation 3
• Annual HBsAg and ALT monitoring thereafter for at least 2-3 years 3
• HBV DNA testing if HBsAg reappears or ALT becomes elevated 3

This monitoring is critical because HBsAg seroreversion (reappearance of HBsAg after seroclearance) can occur, though it is uncommon. 3

Special Considerations

Cirrhotic Patients

Even patients with compensated or decompensated cirrhosis who achieve HBsAg seroclearance can discontinue antiviral therapy, though they require:

• More intensive monitoring with 3-month intervals for HBsAg and ALT during the first year 3
• Continued hepatocellular carcinoma surveillance every 6 months, as the risk of HCC persists even after HBsAg loss, particularly in those with established cirrhosis 3, 1

Duration of Treatment Before HBsAg Loss

The timing of HBsAg seroclearance varies widely:

• Most patients require many years of continuous nucleos(t)ide analogue therapy before achieving HBsAg loss 3
• Prolonged viral suppression (maintaining undetectable HBV DNA) increases the likelihood of eventual HBsAg seroclearance 3, 1
• Tenofovir demonstrates 3.4-4.9% HBsAg loss rates after 10 years of treatment 3

Common Pitfalls to Avoid

• Do not continue antiviral therapy indefinitely after confirmed HBsAg seroclearance, as this provides no additional benefit and represents unnecessary treatment 1, 2
• Do not confuse HBeAg seroconversion with HBsAg seroclearance—these are distinct endpoints with different treatment implications 3, 1
• Do not discontinue monitoring after stopping treatment, as seroreversion and late relapse can occur 3
• Do not stop HCC surveillance in cirrhotic patients who achieve HBsAg loss, as cancer risk remains elevated 3, 1

Quality of Life and Long-Term Outcomes

Achieving HBsAg seroclearance is associated with:

• Improved survival and reduced liver-related mortality 3
• Decreased risk of hepatic decompensation and need for liver transplantation 3
• Reduced stigma and improved quality of life from being functionally cured 3
• Elimination of transmission risk to others 3