Long-term kinetics of quantitative HBsAg levels during successful oral antiviral therapy of chronic hepatitis B

The ultimate goal of antiviral therapy in chronic hepatitis B virus infection is HBsAg seroconversion. Required treatment durations using nucleos(t)ide analogues to achieving this goal are undefined. HBV persistence despite suppression of HBV-DNA is determined by the amount of intrahepatic cccDNA which is reflected by serum HBsAg levels.

We studied 31 patients (mean age 49±11 years) who showed long-term suppression of viral replication during antiviral therapy (HBV-DNA <100 IU/ml) for up to 108 months after start of antiviral treatment (mean follow-up 29±21 months). HBsAg was determined using the Abbott Architect assay. Patients were treated with lamivudine (n=18), adefovir (n=5), entecavir (n=3), tenofovir (n=2) or lamivudine/adefovir combination therapy (n=3).

Median time to complete virological response (HBV-DNA <100 IU/ml or negative qualitative nested PCR) was 6 months. Mean HBsAg levels were 14513±15690 IU/ml at start of therapy and 8810±10516 IU/ml when patients had a complete virological response. During follow up, 14 individuals (45%) had at least a two-fold decline in serum HBsAg levels (“HBsAg responder“) with 16% and 10% showing a >10 or >100 fold HBsAg reduction, respectively. HBsAg responder patients were older (median 55 years vs. 45 years; p=0.02) and had a significantly greater reduction of HBsAg levels already early during therapy before patients became HBV-DNA negative as compared to HBsAg nonresponder (p=0.003). HBV genotype-A was found in all patients experiencing a more than 2xlog10 HBsAg decline. Individual HBsAg kinetics showed rather different courses:

a) constant HBsAg levels despite complete HBV-DNA suppression for up to 4 years,

b) biphasic patterns (constant levels for 2–3 years followed by significant declines thereafter),

c) linear declines starting from the begin of antiviral therapy. One patient became HBsAg negative after 9 years of lamivudine treatment.

Conclusion: More than half of hepatitis B patients do not show significant reductions of HBsAg levels despite virological response for the first 2–4 years of therapy. However, prolonged antiviral therapy may lead to HBsAg clearance in some patients which can be identified by quantitative of HBsAg.