- Email: [email protected]
P0613 : Hepatitis B core related antigen may be a marker for immune control in HBeAg negative chronic hepatitis B infection
POSTERS HBsAg level strongly predict sustained virologic response. NonGG genotype of IP-10 gene promoter polymorphism was linked to low HBsAg level at end-of-therapy. Further study on immunopathophysiology is needed to elucidate this association.
increased in 4 patients (Figure 1). Week 72 HBcrAg was missing in 1 patient. In all 4 patients with HBcrAg increase, viral relapse occurred at week 96. In contrast, viral relapse was observed in only 1/10 patients with HBcrAg decline. In 20 patients who continued ETV between week 72 and 96, HBcrAg declined in 12 patients and increased in 8 patients. No viral relapse occurred in this group. One patient of the PEG-IFN add-on arm who had HBcrAg decline (−0.65 log U/mL) cleared HBsAg at week 96. Overall, mean HBcrAg decline was stronger in patients who previously received PEG-IFN add-on therapy than in patients of the ETV monotherapy arm (−0.29 vs. +0.14 U/mL, p = 0.033). Conclusions: Serum HBcrAg levels declined in the majority of patients with PEG-IFN add-on induced HBeAg loss. HBcrAg increase was predominantly seen during ongoing ETV treatment of patients with ETV-induced HBeAg loss. Viral relapse after ETV cessation only occurred in patients who had HBcrAg increase or minor decrease. HBcrAg may therefore be useful as a marker for immune control in HBeAg negative CHB, but further analysis in larger patient groups is required.
Figure 1.
P0613 HEPATITIS B CORE RELATED ANTIGEN MAY BE A MARKER FOR IMMUNE CONTROL IN HBeAg NEGATIVE CHRONIC HEPATITIS B INFECTION M.J. Van Campenhout1 , W.P. Brouwer1 , H.L. Janssen1,2 , Q. Xie3 , Q. Zhang4 , F. Tabak5 , A. Streinu-Cercel6 , J. Wang7 , G. van Oord1 , R.J. de Knegt1 , A. Boonstra1 , B.E. Hansen1,8 . 1 Gastroenterology and Hepatology, Erasmus MC, University Medical Hospital Rotterdam, Rotterdam, Netherlands; 2 Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, Canada; 3 Infectious Diseases, Ruijin Hospital, Jiaotong University, 4 Gastroenterology and Hepatology, Shanghai Public Health Center, Fu Dan University, Shanghai, China; 5 Cerrahpasa Medical Faculty, Istanbul, Turkey; 6 Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, ¸ Bucharest, Romania; 7 Gastroenterology and Hepatology, Zhong Shan Hospital, Fu Dan University, Shanghai, China; 8 Public Health, Erasmus MC, University Medical Hospital Rotterdam, Rotterdam, Netherlands E-mail: [email protected] Background and Aims: Hepatitis B core related antigen (HBcrAg) is a new serum marker comprised of 3 viral proteins coded by the precore/core region of the covalently closed circular DNA (cccDNA): HBeAg, HBcAg and p22cr. Our aims were to describe HBcrAg kinetics in HBeAg negative chronic hepatitis B (CHB), and to assess if HBcrAg can be used as a marker for immune control in this group. Methods: We measured serum HBcrAg in patients who participated in an international multicenter RCT (ARES study). In this study, 175 HBeAg positive patients all received entecavir (ETV) treatment for 24 weeks, and were then allocated to either continuation of ETV monotherapy or addition of 24 weeks of peginterferon alpha2a (PEG-IFN add-on). Only when combined response (CR; HBeAg loss and HBV DNA <200 IU/mL) was achieved at week 48, patients stopped treatment at week 72. For this post-hoc analysis, we focused on HBcrAg decline between week 72 and 96 in patients who were HBeAg negative in this time interval. Also, viral relapse (HBV DNA >200 IU/mL) was assessed. HBcrAg levels were measured using the Lumipulse® G HBcrAg assay (Fujirebio Europe, Belgium). Results: HBeAg was negative at both week 72 and 96 in 36 patients. In 16/36 patients ETV was stopped at week 72. In this group, HBcrAg levels declined in 10 patients, remained stable in 1 patient and
Figure 1. HBcrAg decline between week 72 and week 96. Bars represent individual log HBcrAg declines grouped by previous therapy. All patients were HBeAg negative between week 72 and 96 and had HBV DNA <200 IU/mL at week 72. Patients in the left panel stopped ETV at week 72, patients in the right panel continued ETV. *Viral relapse at week 96. † HBsAg loss at week 96.
P0614 KEY HBsAg MUTATIONS SIGNIFICANTLY CORRELATE WITH HCC, HAMPER HBsAg SECRETION AND PROMOTE CELL PROLIFERATION IN VITRO M. Surdo1 , R. Salpini1 , N. Warner2 , M.F. Cortese1 , C. Mirabelli1,3 , D. Colledge2 , S. Soppe2 , M. Pollicita1 , R. Longo4 , S. Romano4 , G. Cappiello4 , A. Spano` 4 , P. Trimoulet5 , H. Fleury5 , J. Vecchiet6 , N. Iapadre7 , A. Barlattani8 , A. Bertoli1 , T. Mari9 , C. Pasquazzi10 , G. Missale11 , C. Sarrecchia12 , E. Orecchini13 , A. Michienzi13 , M. Andreoni12 , S. Francioso14 , M. Angelico14 , F. CeccheriniSilberstein1 , S. Locarnini2 , C.-F. Perno1 , V. Svicher1 . 1 Experimental Medicine and Surgery, University of Rome Tor Vergata, Roma, Italy; 2 Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia; 3 Unit´e de Biologie des virus ent´eriques, Institut Pasteur, Paris, France; 4 S. Pertini Hospital, Roma, Italy; 5 Hˆ opital Pellegrin Tripode, Bordeaux, France; 6 “SS Annunziata” Hospital, Chieti, 7 “S Salvatore” Hospital, L’Aquila, 8 “S Giacomo” Hospital, 9 “Regina Margherita” Hospital, 10 “S Andrea” Hospital, Roma, 11 Hospital of Parma, Parma, 12 Infectious Diseases Unit, Tor Vergata University Hospital, 13 Department of Biomedicine And Prevention, University of Rome Tor Vergata, 14 Hepatology Unit, Tor Vergata University Hospital, Roma, Italy E-mail: [email protected] Background and Aims: To investigate HBsAg genetic determinants correlated with HBV-induced hepatocellular carcinoma (HCC) and their impact on cell proliferation. Methods: This study includes 153 HBV chronically infected patients: 15 with HCC (60% D; 33% A, 7% E HBV genotype), and 138 asymptomatic patients as control (58% D, 31% A, 11% E). Mutations were defined according to the reference sequence of each specific HBV genotype. Association of HBsAg mutations with HCC was assessed by Fisher test.
Journal of Hepatology 2015 vol. 62 | S263–S864
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increased in 4 patients (Figure 1). Week 72 HBcrAg was missing in 1 patient. In all 4 patients with HBcrAg increase, viral relapse occurred at week 96. In contrast, viral relapse was observed in only 1/10 patients with HBcrAg decline. In 20 patients who continued ETV between week 72 and 96, HBcrAg declined in 12 patients and increased in 8 patients. No viral relapse occurred in this group. One patient of the PEG-IFN add-on arm who had HBcrAg decline (−0.65 log U/mL) cleared HBsAg at week 96. Overall, mean HBcrAg decline was stronger in patients who previously received PEG-IFN add-on therapy than in patients of the ETV monotherapy arm (−0.29 vs. +0.14 U/mL, p = 0.033). Conclusions: Serum HBcrAg levels declined in the majority of patients with PEG-IFN add-on induced HBeAg loss. HBcrAg increase was predominantly seen during ongoing ETV treatment of patients with ETV-induced HBeAg loss. Viral relapse after ETV cessation only occurred in patients who had HBcrAg increase or minor decrease. HBcrAg may therefore be useful as a marker for immune control in HBeAg negative CHB, but further analysis in larger patient groups is required.
Figure 1.
P0613 HEPATITIS B CORE RELATED ANTIGEN MAY BE A MARKER FOR IMMUNE CONTROL IN HBeAg NEGATIVE CHRONIC HEPATITIS B INFECTION M.J. Van Campenhout1 , W.P. Brouwer1 , H.L. Janssen1,2 , Q. Xie3 , Q. Zhang4 , F. Tabak5 , A. Streinu-Cercel6 , J. Wang7 , G. van Oord1 , R.J. de Knegt1 , A. Boonstra1 , B.E. Hansen1,8 . 1 Gastroenterology and Hepatology, Erasmus MC, University Medical Hospital Rotterdam, Rotterdam, Netherlands; 2 Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, Canada; 3 Infectious Diseases, Ruijin Hospital, Jiaotong University, 4 Gastroenterology and Hepatology, Shanghai Public Health Center, Fu Dan University, Shanghai, China; 5 Cerrahpasa Medical Faculty, Istanbul, Turkey; 6 Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, ¸ Bucharest, Romania; 7 Gastroenterology and Hepatology, Zhong Shan Hospital, Fu Dan University, Shanghai, China; 8 Public Health, Erasmus MC, University Medical Hospital Rotterdam, Rotterdam, Netherlands E-mail: [email protected] Background and Aims: Hepatitis B core related antigen (HBcrAg) is a new serum marker comprised of 3 viral proteins coded by the precore/core region of the covalently closed circular DNA (cccDNA): HBeAg, HBcAg and p22cr. Our aims were to describe HBcrAg kinetics in HBeAg negative chronic hepatitis B (CHB), and to assess if HBcrAg can be used as a marker for immune control in this group. Methods: We measured serum HBcrAg in patients who participated in an international multicenter RCT (ARES study). In this study, 175 HBeAg positive patients all received entecavir (ETV) treatment for 24 weeks, and were then allocated to either continuation of ETV monotherapy or addition of 24 weeks of peginterferon alpha2a (PEG-IFN add-on). Only when combined response (CR; HBeAg loss and HBV DNA <200 IU/mL) was achieved at week 48, patients stopped treatment at week 72. For this post-hoc analysis, we focused on HBcrAg decline between week 72 and 96 in patients who were HBeAg negative in this time interval. Also, viral relapse (HBV DNA >200 IU/mL) was assessed. HBcrAg levels were measured using the Lumipulse® G HBcrAg assay (Fujirebio Europe, Belgium). Results: HBeAg was negative at both week 72 and 96 in 36 patients. In 16/36 patients ETV was stopped at week 72. In this group, HBcrAg levels declined in 10 patients, remained stable in 1 patient and
Figure 1. HBcrAg decline between week 72 and week 96. Bars represent individual log HBcrAg declines grouped by previous therapy. All patients were HBeAg negative between week 72 and 96 and had HBV DNA <200 IU/mL at week 72. Patients in the left panel stopped ETV at week 72, patients in the right panel continued ETV. *Viral relapse at week 96. † HBsAg loss at week 96.
P0614 KEY HBsAg MUTATIONS SIGNIFICANTLY CORRELATE WITH HCC, HAMPER HBsAg SECRETION AND PROMOTE CELL PROLIFERATION IN VITRO M. Surdo1 , R. Salpini1 , N. Warner2 , M.F. Cortese1 , C. Mirabelli1,3 , D. Colledge2 , S. Soppe2 , M. Pollicita1 , R. Longo4 , S. Romano4 , G. Cappiello4 , A. Spano` 4 , P. Trimoulet5 , H. Fleury5 , J. Vecchiet6 , N. Iapadre7 , A. Barlattani8 , A. Bertoli1 , T. Mari9 , C. Pasquazzi10 , G. Missale11 , C. Sarrecchia12 , E. Orecchini13 , A. Michienzi13 , M. Andreoni12 , S. Francioso14 , M. Angelico14 , F. CeccheriniSilberstein1 , S. Locarnini2 , C.-F. Perno1 , V. Svicher1 . 1 Experimental Medicine and Surgery, University of Rome Tor Vergata, Roma, Italy; 2 Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia; 3 Unit´e de Biologie des virus ent´eriques, Institut Pasteur, Paris, France; 4 S. Pertini Hospital, Roma, Italy; 5 Hˆ opital Pellegrin Tripode, Bordeaux, France; 6 “SS Annunziata” Hospital, Chieti, 7 “S Salvatore” Hospital, L’Aquila, 8 “S Giacomo” Hospital, 9 “Regina Margherita” Hospital, 10 “S Andrea” Hospital, Roma, 11 Hospital of Parma, Parma, 12 Infectious Diseases Unit, Tor Vergata University Hospital, 13 Department of Biomedicine And Prevention, University of Rome Tor Vergata, 14 Hepatology Unit, Tor Vergata University Hospital, Roma, Italy E-mail: [email protected] Background and Aims: To investigate HBsAg genetic determinants correlated with HBV-induced hepatocellular carcinoma (HCC) and their impact on cell proliferation. Methods: This study includes 153 HBV chronically infected patients: 15 with HCC (60% D; 33% A, 7% E HBV genotype), and 138 asymptomatic patients as control (58% D, 31% A, 11% E). Mutations were defined according to the reference sequence of each specific HBV genotype. Association of HBsAg mutations with HCC was assessed by Fisher test.
Journal of Hepatology 2015 vol. 62 | S263–S864
S547