Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies

Table 1 Mechanisms of immune cell response in hepatitis B virus reactivation

Immune cells	Mechanism of impairment	Outcomes	Ref.
Innate immune cell responses
Natural killer cells	Downregulation of activating receptors (NKp30, NKp46, and CD56dim), inhibitory cytokine production (IFN- and TNF-)	Reduced viral clearance, increased reactivation risk	[62,64]
Dendritic cells	Reduced antigen presentation (CD8+ CTLs), impaired cytokine (IL-12 and IL-18) production	Impaired antiviral response, increased viral persistence	[40,65]
Macrophages	Dysregulated cytokine secretion (IL-1β, IL-6, and TNF-α)	Altered immune balance, increased inflammation	[49]
Neutrophils	Impaired chemotaxis, reduced phagocytosis	Ineffective pathogen clearance, prolonged viremia	[55]
Adaptive immune cell responses
CD8+ T cells	Exhaustion (CD8+ T cells), reduced cytotoxic activity	Inadequate viral control, viral persistence	[66]
CD4+ T cells	Decreased help for B and CD8+ T cells	Impaired adaptive immune response	[67]
B cells	Altered antibody production	Reduced neutralizing antibodies, prolonged viremia	[68]
Regulatory T cells	Dysfunction, reduced suppression	Dysregulated immune response, increased inflammation	[69]

IL: Interleukin; CTL: CD8+ cytotoxic T lymphocyte; TNF-α: Tumor necrosis factor-alpha; IFN: Interferons.

Table 2 Strategies for the management of hepatitis B virus reactivation

Therapy	Model	Mechanism	Efficacy	Success rate, %	Resistance	Ref.
Anti-viral therapy
Nucleos(t)ide	Lamivudine	Inhibits viral DNA synthesis	High	80%	Low	[30]
	Entecavir	Potent viral DNA polymerase	High	90%	Rare	[120]
	Adefovir	Inhibits viral DNA polymerase	Moderate	70%-80%	Occasional	[128]
	Tenofovir	Inhibits viral DNA synthesis	High	90%	Rare	[124]
Monoclonal antibodies	Anti-HBV antibodies	Viral neutralization	Moderate	70%	Occasional	[137]
Combination therapy	Tenofovir + emtricitabine	Inhibits viral DNA synthesis	High	95%	Low	[138]
Immune-modulating therapy
	Toll-like receptor agonists	Immune activation	Moderate	70%	Variable	[139]
	Interferon	Antiviral and immune activation	High	80%	Occasional	[140]
Personalized treatment approaches
	Tailored	Targeted antiviral therapy based on genomic profile	Variable	75%-90%	Variable	[141]
	Treatment
Combination therapy	Nucleos(t)ide + immune-modulating therapy	Antiviral + immunomodulation	High	90%-95%	Low	[142]
Monoclonal antibodies	Individualized treatment	Targeted viral neutralization based on antibody profiling	Varies	60%-80%	Occasional	[143]