BACKGROUND. The clinical management of chronic hepatitis B virus (HBV) patients is based exclusively on virological parameters that cannot independently determine in which patients nucleos(t)ide-analogue (NUC) therapy can be safely discontinued. NUCs efficiently suppress viral replication, but do not eliminate HBV. Thus, therapy discontinuation can be associated with virological and biochemical relapse and, consequently, therapy in the majority is life-long. METHODS. Since antiviral immunity is pivotal for HBV control, we investigated potential biomarkers for the safe discontinuation of NUCs within immune profiles of chronic HBV patients by utilizing traditional immunological assays (ELISPOT, flow cytometry) in conjunction with analyses of global non–antigen-specific immune populations (NanoString and CyTOF). Two distinct cohorts of 19 and 27 chronic HBV patients, respectively, were analyzed longitudinally prior to and after discontinuation of 2 different NUC therapy strategies. RESULTS. Absence of hepatic flares following discontinuation of NUC treatment correlated with the presence, during NUC viral suppression, of HBV core and polymerase-specific T cells that were contained within the ex vivo PD-1⁺ population. CONCLUSIONS. This study identifies the presence of functional HBV-specific T cells as a candidate immunological biomarker for safe therapy discontinuation in chronic HBV patients. Furthermore, the persistent and functional antiviral activity of PD-1⁺ HBV–specific T cells highlights the potential beneficial role of the expression of T cell exhaustion markers during human chronic viral infection. FUNDING. This work was funded by a Singapore Translational Research Investigator Award (NMRC/STaR/013/2012), the Eradication of HBV TCR Program (NMRC/TCR/014-NUHS/2015), the Singapore Immunology Network, the Wellcome Trust (107389/Z/15/Z), and a Barts and The London Charity (723/1795) grant.

The relationship between stages of chronic hepatitis B liver disease and health-related quality of life (HRQoL) is an important aspect of the overall management of hepatitis B virus (HBV) infection, yet is not well characterized. Consequently we sought to examine HRQoL in HBV patients, stratified by disease severity, compared with normal controls and hypertensive patients, using the Short Form 36 Health Survey (SF-36) and the EQ-5D self-report questionnaire. Univariate and multivariate analyses were then performed. A total of 432 HBV (156 asymptomatic carriers, 142 chronic hepatitis B, 66 compensated cirrhosis, 24 decompensated cirrhosis, 22 hepatocellular carcinoma, and 22 post–liver transplant) patients, 93 hypertensive patients, and 108 normal controls participated in the study. Multivariate analysis showed that normal controls and asymptomatic carriers had similar SF-36 scores, which were better than those for hypertensive patients, but with development of chronic hepatitis B and compensated cirrhosis, showed a significant decrease in general health and the mental dimension, whereas those with advanced liver disease (decompensated cirrhosis and hepatocellular carcinoma) had significantly lower scores in all components (P < 0.05), indicating that the physical component deteriorates only with advanced liver disease. Similar results were obtained with EQ5D. Post–liver transplant patients had similar HRQoL to patients with decompensated cirrhosis and hepatocellular carcinoma, although there was a trend toward improvement. Conclusion: Our results showed that HRQoL in asymptomatic carriers is comparable to those of normal controls and better than hypertensive patients, but deteriorates with disease progression, initially in general health and mental dimensions, but with advanced disease all dimensions are affected. (HEPATOLOGY 2008.)

Introduction: HEPLISAV-B is a hepatitis B vaccine composed of rHBsAg mixed with a synthetic oligonucleotide containing CpG motifs that stimulate innate immunity through TLR9. This vaccine was recently approved by the FDA in view of its superior efficacy. Areas covered: Published literature on HEPLISAV-B was critically reviewed. Four randomized controlled trials among 7,056 subjects receiving 2 doses of HEPLISAV-B and 3,214 subjects receiving 3 doses of Engerix-B showed superior seroprotection rate (SPR) (anti-HBs ≥10 mIU/mL) of 90 - 100%, compared with 71 - 90% in those receiving Engerix-B. Furthermore, the seroprotection rate was also significantly higher in HEPLISAV-B compared with Engerix-B recipients in persons with traditionally poor vaccine response such as older adults, diabetics and those with chronic kidney disease. The safety profiles among 9,871 subjects were similar between HEPLISAV-B and Engerix-B . Expert opinion: HEPLISAV-B, a CpG adjuvant mixed with HBsAg, is more efficacious and produced earlier seroprotection compared to existing vaccines, with a favourable safety profile. The shorter, two-dose regimen, earlier seroprotection, higher adherence and a higher seroprotection rate, especially in populations with traditionally poor vaccine response, makes this an important therapeutic option in hepatitis B vaccination.