OBJECTIVE: To examine viral evolutionary changes and their relationship to hepatitis B e antigen (HBeAg) seroconversion. DESIGN: A matched case-control study of HBeAg seroconverters (n = 8) and non-seroconverters (n = 7) with adequate stored sera before seroconversion was performed. Nested PCR, cloning and sequencing of hepatitis B virus (HBV) precore/core gene was performed. Sequences were aligned using Clustal X2.0, followed by construction of phylogenetic trees using Pebble 1.0. Viral diversity, evolutionary rates and positive selection were then analysed. RESULTS: Baseline HBV quasispecies viral diversity was identical in seroconverters and non-seroconverters 10 years before seroconversion but started to increase approximately 3 years later. Concurrently, precore stop codon (PSC) mutations appeared. Some 2 years later, HBV-DNA declined, together with a dramatic reduction in HBeAg titres. Just before HBeAg seroconversion, seroconverters had HBV-DNA levels 2 log lower (p = 0.008), HBeAg titres 310-fold smaller (p = 0.02), PSC mutations > 25% (p < 0.001), viral evolution 8.1-fold higher (p = 0.01) and viral diversity 2.9-fold higher (p < 0.001), compared to non-seroconverters, with a 9.3-fold higher viral diversity than baseline (p = 0.011). Phylogenetic trees in seroconverters showed clustering of separate time points and longer branch lengths than non-seroconverters (p = 0.01). Positive selection was detected in five of eight seroconverters but none in non-seroconverters (p = 0.026). There was significant negative correlation between viral diversity (rs = -0.60, p < 0.001) and HBV-DNA or HBeAg (rs = -0.58, p = 0.006) levels; and positive correlation with PSC mutations (rs = 0.38, p = 0.009). Over time, the significant positive correlation was viral diversity (rs = 0.65, p < 0.001), while negative correlation was HBV-DNA (rs = -0.627, p < 0.001) and HBeAg levels (rs = -0.512, p =0.015). CONCLUSIONS: Cumulative viral evolutionary changes that precede HBeAg seroconversion provide insights into this event that may have implications for therapy.
OBJECTIVE: To examine viral evolutionary changes and their relationship to hepatitis B e antigen (HBeAg) seroconversion. DESIGN: A matched case-control study of HBeAg seroconverters (n = 8) and non-seroconverters (n = 7) with adequate stored sera before seroconversion was performed. Nested PCR, cloning and sequencing of hepatitis B virus (HBV) precore/core gene was performed. Sequences were aligned using Clustal X2.0, followed by construction of phylogenetic trees using Pebble 1.0. Viral diversity, evolutionary rates and positive selection were then analysed. RESULTS: Baseline HBV quasispecies viral diversity was identical in seroconverters and non-seroconverters 10 years before seroconversion but started to increase approximately 3 years later. Concurrently, precore stop codon (PSC) mutations appeared. Some 2 years later, HBV-DNA declined, together with a dramatic reduction in HBeAg titres. Just before HBeAg seroconversion, seroconverters had HBV-DNA levels 2 log lower (p = 0.008), HBeAg titres 310-fold smaller (p = 0.02), PSC mutations > 25% (p < 0.001), viral evolution 8.1-fold higher (p = 0.01) and viral diversity 2.9-fold higher (p < 0.001), compared to non-seroconverters, with a 9.3-fold higher viral diversity than baseline (p = 0.011). Phylogenetic trees in seroconverters showed clustering of separate time points and longer branch lengths than non-seroconverters (p = 0.01). Positive selection was detected in five of eight seroconverters but none in non-seroconverters (p = 0.026). There was significant negative correlation between viral diversity (rs = -0.60, p < 0.001) and HBV-DNA or HBeAg (rs = -0.58, p = 0.006) levels; and positive correlation with PSC mutations (rs = 0.38, p = 0.009). Over time, the significant positive correlation was viral diversity (rs = 0.65, p < 0.001), while negative correlation was HBV-DNA (rs = -0.627, p < 0.001) and HBeAg levels (rs = -0.512, p =0.015). CONCLUSIONS: Cumulative viral evolutionary changes that precede HBeAg seroconversion provide insights into this event that may have implications for therapy.
Authors: Maria Homs; Andrea Caballero; Josep Gregori; David Tabernero; Josep Quer; Leonardo Nieto; Rafael Esteban; Maria Buti; Francisco Rodriguez-Frias Journal: PLoS One Date: 2014-11-13 Impact factor: 3.240
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
Authors: Maria Homs; Francisco Rodriguez-Frias; Josep Gregori; Alicia Ruiz; Pilar Reimundo; Rosario Casillas; David Tabernero; Cristina Godoy; Salma Barakat; Josep Quer; Mar Riveiro-Barciela; Michael Roggendorf; Rafael Esteban; Maria Buti Journal: PLoS One Date: 2016-06-30 Impact factor: 3.240
Authors: Yuan O Zhu; Pauline P K Aw; Paola Florez de Sessions; Shuzhen Hong; Lee Xian See; Lewis Z Hong; Andreas Wilm; Chen Hao Li; Stephane Hue; Seng Gee Lim; Niranjan Nagarajan; William F Burkholder; Martin Hibberd Journal: BMC Genomics Date: 2017-10-27 Impact factor: 3.969
Authors: Magdalena Świderska; Małgorzata Pawłowska; Włodzimierz Mazur; Krzysztof Tomasiewicz; Krzysztof Simon; Anna Piekarska; Marta Wawrzynowicz-Syczewska; Jerzy Jaroszewicz; Paweł Rajewski; Ewelina Zasik; Elżbieta Murias-Bryłowska; Anna Pniewska; Waldemar Halota; Robert Flisiak Journal: Clin Exp Hepatol Date: 2015-04-30