BACKGROUND: HBV DNA and quantitative (q)HBsAg levels as prognostic markers for HBV-related disease are mostly validated in Asia and their significance in Western populations is uncertain. AIM: To analyse the impact of the HBV genotype and frequent mutations in precore (PC), basal core promoter (BCP) and preS on HBV DNA and qHBsAg levels. METHODS: HBV DNA and qHBsAg serum levels of 465 patients with HBeAg-negative chronic HBV infection were correlated with the HBV genotype and mutations in PC, BCP and preS. For a detailed analysis of the molecular virology, genotype A2 genomes harbouring these mutations were analysed for replication efficacy and HBsAg release in cell culture. RESULTS: While no impact of the HBV genotype on HBV DNA levels was observed, qHBsAg levels differed up to 1.4 log among the genotypes (P < 0.001), reflected by large differences regarding the 1000 IU/mL HBsAg cut-off. While PC mutations were associated with higher (P < 0.001), BCP mutations were associated with lower HBV DNA levels (P < 0.001). Higher qHBsAg levels were associated with preS and lower levels with PC mutations (P < 0.001 and P = 0.001, respectively). The cell culture experiments revealed a higher HBsAg release and shorter filaments in case of a HBV genome harbouring a preS deletion. In contrast, a perinuclear HBsAg accumulation was detected for the PC and BCP-variants, reflecting an impaired HBsAg release. CONCLUSIONS: qHBsAg serum levels depend on the HBV genotype and together with HBV DNA levels on frequent mutations in PC, BCP and preS in HBeAg-negative patients. qHBsAg cut-offs when used as prognostic markers require genotype-dependent validation.
BACKGROUND: HBV DNA and quantitative (q)HBsAg levels as prognostic markers for HBV-related disease are mostly validated in Asia and their significance in Western populations is uncertain. AIM: To analyse the impact of the HBV genotype and frequent mutations in precore (PC), basal core promoter (BCP) and preS on HBV DNA and qHBsAg levels. METHODS: HBV DNA and qHBsAg serum levels of 465 patients with HBeAg-negative chronic HBV infection were correlated with the HBV genotype and mutations in PC, BCP and preS. For a detailed analysis of the molecular virology, genotype A2 genomes harbouring these mutations were analysed for replication efficacy and HBsAg release in cell culture. RESULTS: While no impact of the HBV genotype on HBV DNA levels was observed, qHBsAg levels differed up to 1.4 log among the genotypes (P < 0.001), reflected by large differences regarding the 1000 IU/mL HBsAg cut-off. While PC mutations were associated with higher (P < 0.001), BCP mutations were associated with lower HBV DNA levels (P < 0.001). Higher qHBsAg levels were associated with preS and lower levels with PC mutations (P < 0.001 and P = 0.001, respectively). The cell culture experiments revealed a higher HBsAg release and shorter filaments in case of a HBV genome harbouring a preS deletion. In contrast, a perinuclear HBsAg accumulation was detected for the PC and BCP-variants, reflecting an impaired HBsAg release. CONCLUSIONS:qHBsAg serum levels depend on the HBV genotype and together with HBV DNA levels on frequent mutations in PC, BCP and preS in HBeAg-negative patients. qHBsAg cut-offs when used as prognostic markers require genotype-dependent validation.
Authors: Lucio Boglione; Ilaria De Benedetto; Tommaso Lupia; Jessica Cusato; Giuseppe Cariti; Giovanni Di Perri Journal: Arch Virol Date: 2021-02-12 Impact factor: 2.574
Authors: Pierre Gantner; Laurent Cotte; Clotilde Allavena; Firouzé Bani-Sadr; Thomas Huleux; Claudine Duvivier; Marc-Antoine Valantin; Christine Jacomet; Véronique Joly; Antoine Chéret; Pascal Pugliese; Pierre Delobel; André Cabié; David Rey Journal: PLoS One Date: 2019-04-18 Impact factor: 3.240
Authors: Ana Isabel Gil-García; Antonio Madejón; Irene Francisco-Recuero; Ana López-López; Emiliana Villafranca; Miriam Romero; Araceli García; Antonio Olveira; Rocío Mena; Juan Ramón Larrubia; Javier García-Samaniego Journal: World J Gastroenterol Date: 2019-10-14 Impact factor: 5.742
Authors: Kai-Henrik Peiffer; Catrina Spengler; Michael Basic; Bingfu Jiang; Lisa Kuhnhenn; Wiebke Obermann; Tobias Zahn; Mirco Glitscher; Alessandro Loglio; Floriana Facchetti; Gert Carra; Alica Kubesch; Johannes Vermehren; Viola Knop; Christiana Graf; Julia Dietz; Fabian Finkelmeier; Eva Herrmann; Jonel Trebicka; Arnold Grünweller; Stefan Zeuzem; Christoph Sarrazin; Pietro Lampertico; Eberhard Hildt Journal: JCI Insight Date: 2020-11-19
Authors: María B Pisano; Cecilia G Giadans; Diego M Flichman; Viviana E Ré; María V Preciado; Pamela Valva Journal: World J Gastroenterol Date: 2021-07-14 Impact factor: 5.742