BACKGROUND AND AIMS: HBsAg loss is a desired, but rare, treatment-induced clinical endpoint in chronic hepatitis B (CHB). Few studies have evaluated viral factors contributing to HBsAg loss. METHODS: This study evaluated baseline interpatient sequence diversity across the HBV genome in tenofovir disoproxil fumarate-treated patients who lost HBsAg and compared it to that of control patients with high HBsAg levels throughout therapy. Twenty-one HBeAg+ patients (14 genotype (GT) A and 7 GT D) who achieved HBsAg loss and 27 controls (17 GT A and 10 GT D), were analyzed. Population sequencing was performed on baseline samples and pairwise genetic distances were calculated for 17 overlapping regions across the HBV genome as a measure of interpatient viral diversity. RESULTS:Overall, viral diversity was up to 10-fold higher across GT D patients compared to GT A patients throughout the HBV genome. Within the pol/RT and HBs genes, interpatient viral diversity was significantly lower among HBsAg loss patients for both GT A and D, with the difference driven largely by a reduction in diversity in the small S gene. Conversely, interpatient viral diversity was generally higher in HBsAg loss patients across the HBx gene regulatory elements and precore region. CONCLUSION: In HBsAg loss patients, less interpatient viral diversity was observed within structural-coding regions while specific regions across the HBx and precore genes encoding nonstructural regulatory elements generally displayed higher interpatient viral diversity. These distinct patterns may reflect different responses to adaptive pressure for HBV genomic structural and nonstructural elements.
RCT Entities:
BACKGROUND AND AIMS: HBsAg loss is a desired, but rare, treatment-induced clinical endpoint in chronic hepatitis B (CHB). Few studies have evaluated viral factors contributing to HBsAg loss. METHODS: This study evaluated baseline interpatient sequence diversity across the HBV genome in tenofovir disoproxil fumarate-treated patients who lost HBsAg and compared it to that of control patients with high HBsAg levels throughout therapy. Twenty-one HBeAg+ patients (14 genotype (GT) A and 7 GT D) who achieved HBsAg loss and 27 controls (17 GT A and 10 GT D), were analyzed. Population sequencing was performed on baseline samples and pairwise genetic distances were calculated for 17 overlapping regions across the HBV genome as a measure of interpatient viral diversity. RESULTS: Overall, viral diversity was up to 10-fold higher across GT D patients compared to GT A patients throughout the HBV genome. Within the pol/RT and HBs genes, interpatient viral diversity was significantly lower among HBsAg loss patients for both GT A and D, with the difference driven largely by a reduction in diversity in the small S gene. Conversely, interpatient viral diversity was generally higher in HBsAg loss patients across the HBx gene regulatory elements and precore region. CONCLUSION: In HBsAg loss patients, less interpatient viral diversity was observed within structural-coding regions while specific regions across the HBx and precore genes encoding nonstructural regulatory elements generally displayed higher interpatient viral diversity. These distinct patterns may reflect different responses to adaptive pressure for HBV genomic structural and nonstructural elements.
Authors: Peter A Revill; Thomas Tu; Hans J Netter; Lilly K W Yuen; Stephen A Locarnini; Margaret Littlejohn Journal: Nat Rev Gastroenterol Hepatol Date: 2020-05-28 Impact factor: 46.802
Authors: Luna Colagrossi; Lucas E Hermans; Romina Salpini; Domenico Di Carlo; Suzan D Pas; Marta Alvarez; Ziv Ben-Ari; Greet Boland; Bianca Bruzzone; Nicola Coppola; Carole Seguin-Devaux; Tomasz Dyda; Federico Garcia; Rolf Kaiser; Sukran Köse; Henrik Krarup; Ivana Lazarevic; Maja M Lunar; Sarah Maylin; Valeria Micheli; Orna Mor; Simona Paraschiv; Dimitros Paraskevis; Mario Poljak; Elisabeth Puchhammer-Stöckl; François Simon; Maja Stanojevic; Kathrine Stene-Johansen; Nijaz Tihic; Pascale Trimoulet; Jens Verheyen; Adriana Vince; Snjezana Zidovec Lepej; Nina Weis; Tülay Yalcinkaya; Charles A B Boucher; Annemarie M J Wensing; Carlo F Perno; Valentina Svicher Journal: BMC Infect Dis Date: 2018-06-01 Impact factor: 3.090