Serum Hepatitis B Virus-DNA Levels Correlate With Long-term Adverse Outcomes in Spontaneous Hepatitis B e Antigen Seroconverters

Abstract

(See the editorial commentary by Lau and Wang, on pages 7–9.)

Background. Hepatitis B e antigen (HBeAg) status and serum hepatitis B virus (HBV) DNA levels are major factors affecting the prognosis of adult HBV carriers; however, the impact of viral load on long-term outcomes after spontaneous HBeAg seroconversion remains unclear.

Methods. A total of 390 spontaneous HBeAg seroconverters with a long-term follow-up were enrolled. Serum HBV-DNA levels at 1 year after HBeAg seroconversion were determined, and their correlation with long-term adverse outcomes was explored.

Results. In a mean follow-up of 6.8 years, the average annual incidence rates were 4.4% and 1.9% for HBeAg-negative hepatitis and hepatitis flare, respectively. Compared with patients with HBV-DNA levels <200 IU/mL, the adjusted hazard ratios of HBeAg-negative hepatitis were 2.4 (95% confidence interval, 1.3–4.4), 3.6 (1.8–7.2), and 5.3 (2.8–10.0), respectively, for serum HBV-DNA level of 2000 −2 × 10⁴, 2 × 10⁴ −2 × 10⁵, and ≥2 × 10⁵ IU/mL. In addition, serum HBV-DNA levels were independently associated with HBeAg-negative hepatitis flare, which confirmed their impact on the immune active hepatitis after HBeAg seroconversion.

Conclusions. HBeAg seroconversion may not always confer favorable outcomes. Serum HBV-DNA levels ≥2000 IU/mL at 1 year post HBeAg seroconversion correlate with increased risk of HBeAg-negative hepatitis and hepatitis flare.