Adding peg-interferon to a fully suppressive nucleos(t)ide regimen leads to rapid decrease of quantitative HBsAg in some hepatitis B patients

Objective: Suppression of HBV-DNA by nucleos(t)ide therapy effectively avoids disease progression but requires long-term medication. Therefore, it would desirable to achieve immunological control which is hampered by immunotolerance due to high antigen levels. HBsAg levels can be reduced by long-term nucleos(t)ide treatment, but interferon is known to be much more effective. It is of interest whether the addition of peg-interferon to a fully suppressive nucleos(t)ide treatment may induce immunological control.

Methods: We observed HBsAg levels of twelve patients who had decided to receive additional peg-interferon-alpha2a as an individualized therapy. Current treatment comprised lamivudine (one pt.), lamivudine plus adefovir (two pts.), entecavir (seven pts.), or entecavir plus tenofovir (two pts.). Mean baseline HBs-Ag was 4,695 (range 16–15,120) IU/ml.

Results: In two patients HBsAg continuously declined by -2,6log10 and -3,25 log10 to week 28 and 32 as compared to baseline, respectively. The slope started in week 8 and 16, resp. The first patient was HBe-Ag negative, was infected with genotype D, had a very low initial HBsAg level, and HBV had already been suppressed by entecavir for 27 months. The second patient was HBe-positive, had infection with genotype A, and HBV was fully suppressed for ten months with entecavir plus tenofovir. She had an HBe-antigen seroconversion at week 24 and even developed anti-Hbs at week 32. In all other patients quantitative HBsAg only decreased by 0.07 log10 (range 0.01–0.25 log10) over 8–24 weeks of combination therapy (mean 16 weeks), and therefore, interferon was stopped. Side effects were comparable to interferon-monotherapy.

Discussion: This combination therapy induced a significant decrease in HBsAg in two patients and may lead to long-term immunological control. However, factors predicting success still have to be elucidated which requires further clinical trials and immunological surveys.

immunological control - nucleos(t)ide-interferon combination - quantitative HBs-Ag