48 weeks outcome after cessation of nucleos(t)ide analogue therapy in chronic hepatitis B patients
ANNALS OF HEPATOLOGY
Authors: Gao, Li; Hu, Yue; Shi, Xiaofeng; Li, Xin; Zhang, Dazhi; Ren, Hong
Abstract
Introduction and objective: The aim of the present study was to investigate the significance of serum HBsAg levels in treatment cessation of nucleoside analogues (NAs) in patients with chronic hepatitis B (CHB) infection. Methods: In 158 CHB patients with long-term NAs treatment, 74 patients were in HBeAg negative and had a HBsAg level <1500 IU/mL, 36 of whom were informed and consented to cease NAs. HBsAg, HBV DNA and liver function were examined in the 1st, 3rd, 6th, 9th and 12th month after treatment cessation. Results: The sustained response rate was 88.89% (32/36) within one year after NAs cessation. Sub-group analysis was based on HBsAg levels of patients with NAs cessation, there was no relapse case in 11 patients whose HBsAg <50 IU/mL, and the negative predictive value (NPV) was 100%. Seroconversion of HBsAg occurred in 3 patients. 2 patients from 21 cases whose HBsAg was between 50 IU/mL and 1000 IU/mL relapsed. 2 of 4 patients whose in HBsAg >1000 IU/mL relapsed. HBsAg of patients with a sustained response decreased slowly. In contrast, HBsAg levels increased gradually in relapsed patients, and the increase of HBsAg was precedent to relapses of HBV DNA and ALT. Multivariate analysis suggested that only HBsAg level showed a close correlation with HBV DNA relapses. ROC curve analysis suggested that the increase of HBsAg level in the 3rd and 6th month after NAs cessation had a great predictive value for relapses. Conclusion: Monitoring of base line HBsAg level can predict outcomes of NAs cessation in HBeAg-negative chronic hepatitis B. HBsAg <50 IU/mL has higher predictive values of better sustained responses in HBeAg-negative CHB patients. (c) 2019 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Checkpoint Inhibitors and Therapeutic Vaccines for the Treatment of Chronic HBV Infection
FRONTIERS IN IMMUNOLOGY
Authors: Hoogeveen, Ruben C.; Boonstra, Andre
Abstract
Treatment of chronic hepatitis B virus (HBV) infection is highly effective in suppressing viral replication, but complete cure is rarely achieved. In recent years, substantial progress has been made in the development of immunotherapy to treat cancer. Applying these therapies to improve the management of chronic HBV infection is now being attempted, and has become an area of active research. Immunotherapy with vaccines and checkpoint inhibitors can boost T cell functions in vitro, and therefore may be used to reinvigorate the impaired HBV-specific T cell response. However, whether these approaches will suffice and restore antiviral T cell immunity to induce long-term HBV control remains an open question. Recent efforts have begun to describe the phenotype and function of HBV-specific T cells on the single epitope level. An improved understanding of differing T cell specificities and their contribution to HBV control will be instrumental for advancement of the field. In this review, we outline correlates of successful versus inadequate T cell responses to HBV, and discuss the rationale behind therapeutic vaccines and checkpoint inhibitors for the treatment of chronic HBV infection.