Loss of HBsAg in nucleoside-naive HBeAg(+) chronic hepatitis B patients following treatment with entecavir or lamivudine: evaluation of HBV genotypes

Abstract

BACKGROUND: Spontaneous HBsAg seroclearance has beenestimated to occur at a rate of 0.5 to 1.7% per year. In thephase III study ETV-022, 5.1% of nucleoside-naïve HBeAg(+)chronic hepatitis B (CHB) patients treated with entecavir (ETV)had confirmed HBsAg loss by week 120. In this analysis weevaluated the distribution of confirmed HBsAg loss according tothe hepatitis B virus (HBV) genotype in patients treated with ETVor lamivudine (LVD) in study ETV-022. METHODS: HBeAg(+) nucleoside-naïve adults with CHB, elevated serum alanineaminotransferase (ALT), and compensated liver disease wererandomized to double-blind treatment for up to 96 weeks withETV 0.5 mg/day or LVD 100 mg/day, with up to 24 weeks ofoff-treatment follow-up. HBsAg was measured at regular inter-vals during on- and off-treatment follow-up. For this analysis,confirmed HBsAg loss was defined as HBsAg loss documentedon two consecutive measurements or at last observation,regardless of treatment period. RESULTS: A total of 18 of 354(5.1%) ETV-treated patients and 10/355 (2.8%) LVD-treatedpatients had confirmed HBsAg loss by week 120. Of the 18ETV patients with HBsAg loss, 8 were genotype A, 2 genotypeB, 1 genotype C, 5 genotype D, and 2 genotype F. A higherproportion of patients infected with HBV genotype A or geno-type D lost HBsAg (8.4% and 13.5% respectively) comparedwith patients infected with genotype B or C (2.9% and 0.9%respectively). Similar patterns were observed among the 10LVD-treated patients. Combining both ETV- and LVD-treatedpatients, those infected with HBV genotype A or D were morelikely to lose HBsAg (7.7% and 8.1% respectively) comparedwith patients infected with genotype B or C (2.1% and 0.5%respectively). CONCLUSIONS: Among all patients treated withETV or LVD in study ETV-022, patients infected with HBV geno-type A or D had a higher rate of HBsAg loss than patients withgenotype B or C infection in both treatment arms. Overall,patients treated with ETV had a higher rate of HBsAg lossacross most HBV genotypes compared with LVD-treatedpatients.