Serum Hepatitis B surface antigen levels during five years Entecavir Therapy In Asian Chronic Hepatitis B patients

Poster Session - 07C. Viral Hepatitis B & D: Clinical (Therapy, New Compounds, Resistance)Background: Change in hepatitis B surface antigen (HBsAg) levels during long-term nucleoside analogue therapy in chronic hepatitis B (CHB) has not been well investigated. Aim: To determine the serologic, biochemical, virologic responses and resistance profile of continuous entecavir up to 5 years. Methods: 222 (70.7% male, median age 45 years) CHB patients started on entecavir between July 2005 and November 2007 were recruited. The rates of HBV DNA detectability, hepatitis B e antigen (HBeAg) seroconversion, alanine aminotransferase (ALT) normalization, and entecavir signature mutations up to year 5 were determined. Serum HBV DNA and HBsAg levels were measured by Cobas Taqman and Elecsys II assay respectively. Resistance profile was determined by a line probe assay (LiPA) for patients with detectable HBV DNA. Results: 222, 188, 173, 170 and 156 patients were followed up for 1, 2, 3, 4 and 5 years respectively. The rates of HBV DNA undetectability, HBeAg seroconversion for HBeAg-positive patients and ALT normalization (for patients with elevated baseline ALT) at year 5 were 97.4%, 55.7% and 91.4% respectively. 1 patient developed HBsAg seroclearance at year 2. 2 patients developed entecavir signature mutations at years 3 and 5 (rt180M, rt204V, rt184S/C/G/A and rt180M, rt204V, rt184I/L/F/M, rt202G, rt250V respectively), resulting in a cumulative resistance of 1.2% up to year 5. Among patients with 5 years of follow-up (n = 156), the median annual HBsAg decline was 0.116 (range −0.176 to 0.980) log IU/mL/year with HBeAg-positive patients having a greater median HBsAg decline when compared to HBeAg-negative patients (0.141 and 0.097 log IU/mL/year respectively, p = 0.021). Patients with significant HBsAg decline, defined as >0.25 log IU/mL/year (n = 31), when compared to patients without significant HBsAg decline, was associated with younger median age (43.5 and 49.3 years respectively, p = 0.014), HBeAg-positivity (54.8% and 34.7% respectively, p = 0.039), and higher median baseline HBV DNA levels (7.99 and 6.22 log IU/mL respectively, p