Low incidence of hepatitis B e antigen seroconversion in patients treated with oral nucleos(t)ides in routine practice

Background and Aim Treatment end-point of therapy for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) includes HBeAg seroconversion, which ranges from 15% to 22% after 1 year of oral nucleos(t)ides according to clinical trials. Our goal was to determine the incidence and predictors of HBeAg seroconversion in such patients in routine clinical practice because they may differ than reported rates. Methods We conducted a retrospective cohort study of 333 consecutive treatment-naive HBeAg-positive patients who were treated for CHB between 1/2000 and 6/2010 at three gastroenterology and liver clinics in the USA. Primary study end-point was HBeAg seroconversionloss of HBeAg and antibody to HBeAg (anti-HBe) development. Results The majority of patients were Asian (96%). Median treatment duration prior to HBeAg seroconversion was 50 (range 2652) weeks. Of the 333 study patients, 25% received lamivudine, 16% adefovir, 51% entecavir, and 8% tenofovir. HBeAg seroconversion at month 12 was 8.2%. On multivariate analysis inclusive of age, gender, and antiviral agents, independent predictors for HBeAg seroconversion at month 12 were hepatitis B virus DNA <7.5 log10IU/mL (hazard ratio [HR]=2.59 [1.046.44]), P=0.041) and alanine transaminase (ALT) >1.5xupper normal limit (HR=2.86 [1.057.81], P=0.040), but not the choice of nucleos(t)ides. Conclusions The HBeAg seroconversion rate seen in clinical settings for oral nucleos(t)ides appears much lower than those reported in pivotal trials, especially in patients with lower ALT and higher HBV DNA levels. HBeAg-positive patients should be counseled about the high possibility of the long treatment duration required to achieve recommended treatment end-points.