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Quest for immunological biomarkers in the management of CHB patients
  1. Antonio Bertoletti,
  2. Nina Le Bert
  1. Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
  1. Correspondence to Professor Antonio Bertoletti, Duke-NUS Medical School, Singapore, Singapore; antonio{at}

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Control of hepatitis B virus (HBV) infection requires functional virus-specific T cells, yet clinical management of patients with chronic HBV infection (CHB) relies exclusively on the assessment of virological (HBV-DNA, HBsAg) and biochemical (alanine transaminase (ALT)) biomarkers. There is, however, a growing recognition of the necessity to categorise CHB patients based on their profile of HBV-specific immunity. Such immunological biomarkers might guide when to start or stop nucleos(t)ide analogue (NA) therapy, and/or identify patients who would benefit from novel therapeutic strategies designed to modify host–virus interaction by restoring HBV-specific immunity, either directly (therapeutic vaccines or check point inhibitors) or indirectly (antisense nucleotides, siRNA) (figure 1).

Figure 1

Immune biomarker for selection of CHB patients: virological (HBV-DNA, HBsAg) and biochemical (ALT) biomarkers have been used to categorise CHB patients. The analysis of immune parameters, like the exhaustion score (ES) proposed by Rossi et al,1 can guide the selection of CHB patients more responsive to novel immunotherapies. ALT, alanine transaminase; CHB, chronic hepatitis B virus infection.

In Gut, Ferrari and Boni’s group present findings which could potentially help address this unmet clinical need.1 Their study in treatment naïve CHB patients shows that simple phenotypic analysis of total circulating CD8T cells can predict HBV-specific CD8 T cell response to immunomodulatory compounds.

For three decades, we have known that HBV-specific T cell immunity differs between patients with acute and CHB (reviewed in Chisari and Ferrari 2). More recent works have shown that HBV-specific T cells recover, even though often only partially,3 4 after functional cure.5 6 Such data support the idea that restoration of functional HBV-specific T cell immunity can achieve HBV control but fails to take into account a key characteristic of HBV-specific T cells in CHB patients: their extreme heterogeneity.3 7–9

Although extremely low levels of HBsAg …

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  • Contributors Both authors equally contributed to the manuscript.

  • Funding This publication was supported by the Singapore Ministry of Health’s National Medical Research Council MOH-000019 (MOH-StaR17Nov-0001).

  • Competing interests AB and NLB reported a patent for a method to monitor SARS-CoV-2-specific T cells in biological samples pending and are the co-founders of T Cell Diagnostic (TCD).

  • Provenance and peer review Commissioned; internally peer reviewed.

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