Figure S1. The clinical courses of patients included in this study. The longitudinal data of 5 ETV- (A) and 2 TDF- (B) treated CHB patients are plotted. Black horizontal bar to the top, time-periods when HBeAg was positive; black triangles, time-points when serum samples were obtained before NAs; grey triangles, time-points when serum samples were obtained at relapse after NA withdrawal; black arrows, time-points when patients started to receive NAs; grey arrows, time-points when NAs were withdrawn; black circles, HBV-DNA levels; grey squares, ALT levels. Figure S2. The HBV genetic heterogeneity in the surface gene analyzed by deep-sequencing. (A) The distribution of well-defined functional domains within the surface gene. I, transmembrane domain I (TMD I: s8-22); cytosolic loop (CL: s22-80); II, transmembrane domain II (TMD II: s80-100); major hydrophilic region (MHR: s99-169); antigenic determinant (a determinant) region (located within MHR: s124-147); III, transmembrane domain III (TMD III: s170-192); IV, transmembrane domain IV (TMD IV: s202-224); hydrophobic C-terminus region (HCR: s170-226, includes TMD III-IV and the loop between them). The surface gene variants identified from ETV-treated patients are listed in (B) while those identified from TDF-treated patients are listed in (C). Baseline, samples obtained from patients before antiviral treatments; Relapse, samples obtained from patients with virological reactivation after NA withdrawal. Figure S3. The viral genetic variations in the reverse transcriptase domain of the polymerase gene analyzed by deep-sequencing. (A) The functional motifs in the reverse transcriptase domain. G, box G or box I; F, F box or box II: rt37-47; A, box A: rt75-90; B, box B: rt159-182; C, box C: rt201-210; D, box D: rt230-241; E, box E: rt247-257. The variants in the reverse transcriptase domain identified from ETV-treated patients are listed in (B) while those identified from TDF-treated patients are listed in (C). Baseline, samples derived from patients before antiviral treatment; Relapse, samples derived from patients with virological relapses after NA withdrawal.