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Hepatitis B Patients with HBeAg Seroconversion on Treatment May Not Have Durable Response


People with chronic hepatitis B virus (HBV) who achieve hepatitis B "e" antigen (HBeAg) seroconversion when treated with nucleoside/nucleotide analogs are more likely to experience HBeAg seroreversion and HBV reactivation than those with natural clearance, according to a study described in the November 15, 2012, Journal of Infectious Diseases.

About 10% of people infected with HBV as adults and 90% of those infected at birth develop chronic hepatitis B, while the remainder experience spontaneous viral clearance without treatment. During natural clearance, loss of HBeAg in the blood and development of anti-HBe antibodies -- known as HBeAg seroconversion -- indicates resolution of active disease.

Several nucleoside and nucleotide analogs -- including lamivudine (Epivir-HBV), adefovir (Hepsera), entecavir (Baraclude), and tenofovir (Viread) -- are effective against HBV. Treatment response includes reduction of HBV DNA levels and in some people, HBeAg loss and seroconversion. It is not clear, however, if HBeAg seroconversion due to nucleoside/nucleotide therapy has a prognosis similar to that of spontaneous HBeAg seroconversion.

Tai-Chung Tseng from Buddhist Tzu Chi General Hospital in Taipei and colleagues looked at disease progression in 148 hepatitis B patients with nucleoside/nucleotide analog-induced HBeAg seroconversion (465 total person-years of follow-up), comparing them against a historical control group of 407 people with spontaneous HBeAg seroconversion (1653 total person-years of follow-up). None of the participants had liver cirrhosis.

Because spontaneous seroconverters were younger at the time of HBeAg seroconversion than those with nucleoside/nucleotide-induced seroconversion, the researchers compared the 2 cohorts according to their age at seroconversion.


  • Among people who achieved HBeAg seroconversion before age 30, those with nucleoside/nucleotide-induced seroconversion were significantly more likely to experience HBV seroreversion (reappearance of HBeAg) by year 2, with rates of 12% vs 3%, respectively.
  • People with drug-induced seroconversion were also more likely to experience HBV reactivation, with a hazard ratio of 4.6, or nearly 5-fold higher risk.
  • In a multivariate analysis, nucleoside/nucleotide-induced HBeAg seroconversion remained a risk factor for both endpoints in young seroconverters after controlling for other factors.

"[Nucleoside/nucleotide]-induced HBeAg seroconverters may not have durable response after stopping therapy," the study authors concluded. "For patients achieving HBeAg seroconversion before 30 years of age, the risk of HBeAg seroreversion and HBV reactivation is higher in [nucleoside/nucleotide]-induced seroconverters than spontaneous HBeAg seroconverters."



T-C Tseng, C-J Liu, T-H Su, J-H Kao, et al. Young Chronic Hepatitis B Patients With Nucleos(t)ide Analogue-induced Hepatitis B e Antigen Seroconversion Have a Higher Risk of HBV Reactivation. Journal of Infectious Diseases 206(10):1521-1531. November 15, 2012.