Revised: July 31, 2026
Accepted: August 14, 2026
Published online: September 27, 2026
Processing time: 83 Days and 23.3 Hours
Pegylated interferon (PEG-IFN) alpha, an important agent for chronic hepatitis B (CHB), exerts antiviral and immunomodulatory activities and serves as a core therapy to pursue functional cure. However, there are significant individual diffe
Core Tip: Currently, patient selection for pegylated interferon (PEG-IFN) therapy predominantly relies on virological markers, which fail to fully recapitulate host immune competence. This review highlights that hepatitis B virus-specific T cells constitute core immune biomarkers predictive of treatment response and functional cure. Synthesizing available evidence concerning T cell exhaustion, regenerative potential, effector function and comprehensive immune profiling, we propose that future patient selection algorithms should transition from virology-only criteria toward immune stratification strategies. This conceptual framework underpins the development of precision PEG-IFN therapy for chronic hepatitis B.
- Citation: Tian B, Tian C, Shen CL, Zhang Q. From virological selection to immune stratification: Hepatitis B virus-specific T cells for precision pegylated interferon therapy in chronic hepatitis B. World J Hepatol 2026; 18(9): 124884
- URL: https://www.wjgnet.com/1948-5182/full/v18/i9/124884.htm
- DOI: https://dx.doi.org/10.4254/wjh.124884
As of 2022, approximately 254 million people worldwide had suffered from chronic hepatitis B virus (HBV) infection, with a prevalence of about 3.2%[1-3]. The HBV remains the leading cause of cirrhosis and hepatocellular carcinoma (HCC), with more than half of HCC cases caused by hepatitis B, and 66% of deaths related to chronic viral hepatitis attributed to hepatitis B infection[4,5]. The dynamic interplay between HBV and the host immune system shapes the progression of chronic hepatitis B (CHB). This interplay determines the phases of the natural history of CHB, treatment efficacy, and long-term prognosis[5-7]. Although nucleos(t)ide analogues can strongly inhibit HBV replication, they are difficult to induce the body to generate sustained antiviral immune control. Clinical data show that patients’ serum hepatitis B surface antigen (HBsAg) clearance levels remain relatively low whether nucleos(t)ide analogue therapy is continued as a standard treatment (with a 10-year HBsAg clearance rate of only 3%-5%), or during the follow-up period after drug withdrawal (an overall HBsAg clearance rate of 8%-13%)[8,9]. Unlike nucleos(t)ide analogues, pegylated interferon α (PEG-IFN-α) possesses both antiviral and immunomodulatory effects, allowing some patients to achieve sustained immune responses[10]. However, the overall efficacy of this drug is limited, and there are adverse reactions. Moreover, existing clinical indicators (such as HBV DNA and quantitative HBsAg) only reflect the level of viral replication activity. They cannot accurately assess the state of the body’s immune response.
HBV-specific T cells are immune cells that recognize HBV antigens and play a central role in viral clearance and disease pathogenesis. HBV-specific CD8 T cells can eliminate infected hepatocytes through cytolytic and non-cytolytic mechanisms, the latter of which includes the secretion of cytokines such as interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). In contrast, HBV-specific CD4 T cells are primarily responsible for initiating and maintaining an effective CD8 T cell response and for mediating the production of specific antibodies. Current studies have confirmed that HBV-specific T cells in the peripheral blood of patients with CHB generally exhibit functional exhaustion; restoring their immune function is a core therapeutic strategy for achieving functional cure of CHB[6,11]. Therefore, dynamic monitoring of HBV-specific T cell responses has been increasingly used in disease evaluation and treatment stratification. Several platforms can be applied to quantify HBV-specific T cell responses, including enzyme-linked immunospot (ELISpot) assays, intracellular cytokine staining (ICS), activation-induced marker assays, peptide-HLA multimer staining, and recently developed standardized peptide pool technologies. Each method exhibits its unique strengths and limitations[12-14]. In this context, our research group has established a scalable ELISpot platform based on optimized HBV peptide pools, enabling routine assessment of HBV-specific T cell responses in patients with CHB[15].
The functional restoration of HBV-specific T cells is observed only in certain patient populations. Existing evidence indicates that host age, duration of antigen exposure, and the level of viral control collectively influence the differentiation and distribution of HBV-specific exhausted T cell subsets. Younger patients or those with lower antigen loads are more likely to retain an exhausted subset with stem-like features. In contrast, T cells exposed to high antigen levels for extended periods tend to become terminally exhausted and respond poorly to interventions[7,16-18]. Therefore, accurately identifying patients with the potential for HBV-specific T cell recovery before PEG-IFN treatment has become a key issue for the precise delivery of PEG-IFN therapy. This article explores the predictive potential of CHB-specific T cells for PEG-IFN treatment, providing ideas for improving the management model of PEG-IFN therapy (Figure 1).
To synthesize evidence for this narrative review, a PubMed search of English publications up to May 2026 was conducted with keywords: “chronic hepatitis B”, “HBV-specific T cells”, “pegylated interferon”, “functional cure”, “ELISpot”, and “immune biomarkers”. We included original studies, translational research and high-quality reviews on HBV-specific T-cell biology and PEG-IFN therapy, and excluded conference abstracts, duplicate articles and manuscripts lacking adequate methodological information. Reference lists were manually screened for additional eligible studies.
Most CHB patients still have detectable HBV-specific CD8 T cells in peripheral blood, but their frequencies and functional capacities are substantially impaired. Existing evidence suggests that this impaired response is due not only to insufficient generation but also to the combined effects of high HBV antigen load, intrahepatic retention, and apoptotic clearance[16,19,20]. Hepatocytes, as non-professional antigen-presenting cells, present antigens to HBV-specific CD8 T cells with relatively low efficiency due to inadequate expression of major histocompatibility complex class I and co-stimulatory molecules, resulting in insufficient or abnormal stimulation of CD8 T cells and eventually leading to HBV-specific T cell exhaustion. Non-parenchymal liver cells further establish a multi-layered immunosuppressive network: The immunosuppressive effect of Kupffer cells; natural killer cell-mediated apoptosis of HBV-specific T cells; and the immunomodulatory function of liver sinusoidal endothelial cells. These mechanisms work synergistically, severely limiting the proliferation, functional differentiation, and reactivation capacity of HBV-specific T cells, which is the core mechanism of immune evasion in chronic HBV infection. In addition, microcirculatory structural changes induced by liver fibrosis can also attenuate the migratory efficiency of HBV-specific T cells[11,21-24]. Therefore, the fundamental reason for the reduced number of HBV-specific T cells in patients with CHB is cellular redistribution and functional depletion due to persistent antigen stimulation, rather than an absolute deficiency.
The core immunological feature of persistent CHB infection is the functional exhaustion of HBV-specific T cells, which is characterized by sustained high expression of inhibitory receptors such as PD-1, TIM-3, LAG-3, and CD160, along with reduced secretion of IFN-γ, TNF-α, and interleukin (IL)-2, decreased proliferative capacity of HBV-specific T cells, and weakened cytotoxicity[25,26]. It is noteworthy that HBV-specific exhausted T cells undergo a differentiation progression from progenitor-like exhausted T (Tpex) cells with self-renewal capacity to terminally exhausted T cells (Terminal Tex). The former still retain a certain degree of functional plasticity and constitute a key cellular basis for immune restoration and therapeutic response in the body; the latter, however, are in a fixed exhausted state with minimal potential for functional recovery[16,27,28]. More importantly, there is significant heterogeneity in T cell exhaustion status among patients, a feature that can serve as an important predictor of the efficacy of PEG-IFN-α therapy[29].
In addition to immunosuppressive signals, HBV-specific T cells undergo functional exhaustion accompanied by signifi
Persistent stimulation by HBV antigens can induce HBV-specific T cells to enter an exhaustion program, a process accom
PEG-IFN-α can not only inhibit HBV replication but also significantly remodel patients’ adaptive immune responses. Studies have shown that PEG-IFN-α treatment can promote the expansion of Th1- and Th17-oriented HBV-specific CD4 and CD8 T cells, partially reversing T-cell unresponsiveness to viral antigen stimulation in chronic HBV infection. In the early phase of treatment (the first 8 weeks), HBV surface (S) and core antigen-specific CD4 T cell responses can be significantly enhanced, suggesting that PEG-IFN-α can rapidly initiate virus-specific immune recovery[36,37].
As treatment continues, HBV-specific T cells not only increase in number but also significantly improve their functional status. Research has found that patients undergoing PEG-IFN-α combination therapy can maintain enhanced multispecific and polyfunctional T cell responses 24 weeks after treatment cessation, with this improvement being particularly notable in patients with a larger decline in HBsAg levels and lower baseline hepatitis B core-related antigen (HBcrAg) levels. For patients who ultimately achieve HBsAg clearance, their peripheral blood HBV-specific T cells can be effectively expanded in vitro and exhibit broad, strong antiviral effector functions, further suggesting that T-cell immune restoration is a key foundation for achieving functional cure[38].
Recent single-cell transcriptome studies have further elucidated the mechanism of PEG-IFN-α-induced immune remodeling. During treatment, the proportion of long-lived naïve/memory T cell subsets increases, the cytotoxicity of effector T cells is enhanced, and the overall immune cell transcriptional profile shifts from a TNF signal-dominated inflammatory state to an IFN-α signal-dominated antiviral state, indicating that PEG-IFN-α can reconstruct an immune microenvironment more conducive to virus clearance[39].
Notably, patients achieving functional cure display distinct dynamic changes in T cell exhaustion compared with treatment non-responders. At week 24 of therapy, the frequencies of PD-1+CD8 T cells and CD160+CD8 T cells in cured individuals remain nearly equivalent to baseline values (0.97-fold and 0.95-fold of baseline, respectively). In contrast, these exhausted T cell subsets are markedly elevated in non-responders. Collectively, these observations indicate that partially reversible T cell exhaustion constitutes a critical immune hallmark linked to favorable interferon therapeutic outcomes[40]. Additionally, patients achieving functional cure show enrichment of the CD300A CD8 T cell population in vivo. This subset highly expresses cytotoxic molecules such as GZMB, PRF1, and GNLY and exhibits stronger effector functions, potentially representing a key antiviral effector cell population closely associated with HBsAg clearance[29].
Recent studies have found that even patients with similar virological characteristics exhibit significant differences in the composition of HBV-specific T cells[16,41,42]. These differences may determine the extent of benefit from PEG-IFN treatment. Patients dominated by terminally exhausted subsets are unlikely to establish sustained immune control, even when receiving a standard course of PEG-IFN treatment. This suggests that the functional status of T cells may more accurately reflect the patient’s true therapeutic potential than conventional virological indicators.
With the development of single-cell sequencing, multiparameter flow cytometry, and immunomics, HBV-specific T cell-related biomarkers can generally be categorized into exhaustion-phenotype markers, restoration-potential markers, functional markers, and multiparameter comprehensive immune scoring/immune typing[16,19,42-44]. The application of these biomarkers in predicting PEG-IFN efficacy is receiving increasing attention (Table 1). Table 1 assesses the predictive value and clinical feasibility of each biomarker via a five-star qualitative rating scale (1 to 5), with one star representing the lowest level and five stars the highest. Ratings were determined comprehensively according to the consistency of available evidence, biological rationale and current clinical applicability. This grading scheme serves only as an evidence summary and does not represent a standardized, validated scoring system.
| Biomarker category | Representative markers | Biological significance | Predictive value score (1-5) | Clinical feasibility score (1-5) |
| Virological markers | HBsAg, HBcrAg | Antigen burden | 4 | 5 |
| Exhaustion markers | PD-1, TOX, CD160 | Degree of T cell exhaustion | 3 | 2 |
| Recovery-potential markers | TCF-1, CD127, Bcl-2 | Tpex cell reservoir reserve | 5 | 2 |
| Functional markers | IFN-γ, TNF-α | Actual effector functionality | 4 | 1 |
| Composite score | Exhaustion index | Comprehensive immune status | 5 | 3 |
Exhaustion markers: During chronic HBV infection, sustained antigen stimulation gradually drives HBV-specific T cells into an exhausted state. Therefore, the expression levels of exhaustion-related molecules are considered to reflect the degree of immunosuppression in patients. The most widely studied indicators currently include PD-1, TOX, CD160, TIM-3, and LAG-3[16,19,25,45]. Among them, PD-1 is the classic exhaustion marker, continuously and highly expressed in HBV-specific CD8 T cells from patients with CHB. It is closely associated with decreased IFN-γ production and impaired proliferative function[46,47]. TOX is considered a key regulator of the exhaustion transcriptional program, and its high expression typically indicates a more stable, difficult-to-reverse state of exhaustion[19,48]. Recent studies have found that the predictive value of a single exhaustion molecule is limited, whereas the combined assessment of multiple exhaustion molecules better reflects the true immune status[16,49]. Therefore, exhaustion-related markers are more suitable as important indicators for evaluating the degree of immunosuppression and the upper limit of treatment benefit in patients, rather than being used alone to inform PEG-IFN treatment decisions.
Recovery-potential markers: Unlike exhaustion markers, recovery-potential markers are mainly used to identify HBV-specific T cell populations that still retain functional plasticity. Recent studies have shown that Tpex are the most important functional reservoir cells in chronic viral infections. These cells typically express molecules such as TCF-1, CD127, and Bcl-2, retaining the ability for self-renewal and the potential to further differentiate into effector cells. Compared with Terminal Tex, Tpex cells are more sensitive to decreased antigen load and immune-modulatory treatment. They are therefore considered an important cellular basis determining therapeutic response[16,50-53]. Among these, TCF-1 is regarded as the most representative marker of recovery potential. Studies have found that the higher the proportion of TCF-1+ HBV-specific CD8 T cells, the stronger their in vitro proliferative capacity and cytokine production, and the more likely they are to regain function during treatment[50,52,53]. CD127 and Bcl-2 can be used to assess the long-term survival capacity and memory differentiation potential of cells[53]. Therefore, identifying whether patients retain a sufficient pool of Tpex cells in vivo provides a more accurate reflection of their true potential benefit from PEG-IFN therapy than merely evaluating the exhaustion level of HBV-specific T cells.
Functional markers: Evaluating HBV-specific T-cell function involves multiparameter assessment of activation phenotype, antiviral effector function, exhaustion/differentiation state, transcriptional regulation, and metabolic fitness. Commonly studied features include CD69 and CD38 expression, cytokine production, such as IFN-γ and TNF-α, transcription factors, including Eomes, TOX, T-bet, and TCF1, and metabolic abnormalities, such as nicotinamide adenine dinucleotide (NAD) depletion, mitochondrial dysfunction, and altered cAMP-PKA signaling[16,27,34,47,54]. Cytokine production capacity is a core feature of functional T cells. For CD8 T cells, IFN-γ and TNF-α are the main antiviral cytokines, produced at high levels during acute, self-limiting infections but at impaired levels during chronic infections. Multifunctional T cells (producing IFN-γ, TNF-α, and IL-2 simultaneously) are considered markers of a more effective antiviral immune response[14,25,54]. In CD4 T cells, the IFN-γ- producing subset is associated with viral clearance and functional cure. In contrast, the TNF-α-producing type is predominant in patients with chronic infection. It is associated with liver damage, and its frequency is positively correlated with alanine aminotransferase and total bilirubin levels[55,56]. Regarding transcription factors, T-bet is highly expressed in functional T cells. At the same time, Eomes expression is elevated in functionally impaired polymerase-specific CD8 T cells, promoting co-expression of inhibitory receptors by enhancing the transcription factors NFATc1, Blimp1, and FoxO1[25,28]. CD127 (IL-7Rα), as a memory T cell marker, is downregulated in functionally impaired T cells, while KLRG1, a terminal differentiation marker, is upregulated[16,28]. Metabolic dysfunction is an important feature of T cell dysfunction, including increased reactive oxygen species levels, NAD depletion, telomere shortening, protein oxidation, and DNA damage; these metabolic defects are interconnected, forming a vicious cycle that sustains CD8 T cell dysfunction[34]. It is noteworthy that T cells targeting different HBV antigens exhibit significant heterogeneity. Core-specific CD8 T cells tend to retain relatively better functionality. In contrast, polymerase-specific CD8 T cells show more pronounced functional impairment, characterized by high expression of CD38, KLRG1, and Eomes, and low expression of T-bet and CD127. These functional markers can be used to assess patients’ immune status, predict therapeutic responses, and guide the development of personalized immunotherapy strategies[42].
Comprehensive immune scoring: Currently, many studies have identified candidate biomarkers associated with the functional status of HBV-specific T cells, but no single indicator has clear utility for clinical prediction. The fundamental reason is that HBV-specific T cell dysfunction results from the interplay of four factors: Persistent antigen stimulation, the establishment of exhaustion programs, retention of functional reserves, and the immune microenvironment, which exhibit high heterogeneity and multidimensional characteristics. Although high PD-1 expression is an important marker of T cell exhaustion, a growing number of studies indicate that the functional impairment of PD-1-positive HBV-specific T cells is not entirely irreversible. Some cells still retain proliferative capacity and potential for functional recovery, especially after antigen load is reduced or following immunomodulatory treatment. The exhausted T cell subset with progenitor-like characteristics still has the opportunity to regain antiviral function. Therefore, relying solely on PD-1 expression levels makes it difficult to accurately assess patients’ true immune status[16,47,57]. Similarly, TCF-1, a marker of restorative potential, is highly expressed, indicating that HBV-specific T cells retain the ability to self-renew and differentiate. However, patients may not necessarily achieve a clinical response. If the patient simultaneously experiences persistent high-level viral antigen exposure, a severely immunosuppressive microenvironment, or significant functional defects, even a relatively high proportion of TCF-1-positive cells may not ensure a complete immune recovery process[50,51,58].
Traditional virological indicators also face similar problems. Lower levels of HBsAg or HBcrAg are usually associated with milder antigen stimulation and better treatment response. Yet, in clinical practice, some patients with low HBsAg levels fail to achieve HBsAg clearance, whereas others with relatively higher antigen levels can achieve functional cure following PEG-IFN treatment[38,59-62]. This result indicates that virological indicators reflect only antigen load and cannot directly determine whether the host’s immune function can be restored. Therefore, when evaluating HBV-specific T cells, a multidimensional comprehensive assessment system should be established. Subsequent studies should synchronously integrate multiple detection indicators: Viral load indicators include HBsAg and HBcrAg; immune exhaustion markers include PD-1, TOX, CD160, etc.; indicators of immune restoration potential include TCF-1, CD127, Bcl-2; at the same time, the levels of cytokine secretion, such as IFN-γ, TNF-α, and IL-2, should be combined to evaluate cellular immune function. A multi-indicator combination can objectively restore the true phenotype of virus-specific T cells in patients. Based on this approach, a comprehensive immune-scoring model can overcome the shortcomings of relying on a single predictive indicator, identify the favorable population for PEG-IFN treatment, and achieve more precise immune stratification and more accurate efficacy predictions. For example, existing studies have developed an exhaustion index (EI) based on phenotypic markers such as PD-1, TOX, CD127, and Bcl-2 to assess the functional recovery potential of HBV-specific CD8 T cells[16].
Currently, a standardized HBV-specific T cell detection system is not available owing to high heterogeneity and poor comparability of test results, which limit clinical application. First, T cell functional assays, such as ELISpot and ICS, are difficult to standardize. Experimental parameters, including cell incubation time, cell seeding density, antigen concentration and type, and the fresh/cryopreserved status of peripheral blood mononuclear cells, vary significantly across different laboratories, making it difficult to compare results across different studies[63,64]. Second, most current studies lack standard operating procedures, comprehensive quality control systems, and standardized operator training, thereby failing to meet quality control requirements for sample preservation, transportation, storage, manual operations, and experimental systems. Third, the HBV-specific T cell assay lacks a minimal core parameter set for immune monitoring and a modular expansion framework. While such a framework has been widely applied in CAR-T technology, where scalable, standardized monitoring protocols were established via the Delphi method, its absence here makes it difficult to ensure the consistency of HBV-specific T cell assays across different centers[65]. Fourth, even if a standardized HBV-specific T cell assay system is established, challenges remain, such as strict technical requirements, substantial personnel training costs, and expensive equipment.
Due to the presence of immune compartments, HBV-specific T cell responses differ significantly between the liver and peripheral blood. Consequently, peripheral blood assay results cannot accurately represent the intrahepatic immune status. HBV-specific T cells are significantly enriched in the liver compared to peripheral blood, and the liver harbors multiple unique T cell subsets that are poorly represented in peripheral blood, including IL-2-producing tissue-resident CD8 T cells and cytotoxic CD4 T cells. Although the phenotypes of HBV-specific T cells in the peripheral blood and the liver share certain mirroring characteristics, the unique intrahepatic immune microenvironment can reshape T cell function through various regulatory factors, such as PD-L1 and myeloid-derived suppressor cells, resulting in significant differences in T cell function between the liver and peripheral blood[24]. Nevertheless, detecting peripheral blood T cells remains clinically valuable. In various immunotherapy scenarios, the characteristics of circulating specific T cells can effectively predict clinical outcomes. However, the discrepancy between the peripheral blood and the intrahepatic immune environment must be fully considered in clinical settings.
Several HBV-specific T cell-associated biomarkers have been preliminarily investigated, but high-quality evidence supporting their generalizability and clinical feasibility remains lacking. The EI and simplified phenotypic scores, constructed based on T cell exhaustion-associated molecules (such as PD-1, TOX, CD127, and Bcl-2), can effectively predict the functional recovery capacity of HBV-specific CD8 T cells in response to immunomodulatory agents in vitro.
However, as most studies are cross-sectional analyses or in vitro functional assays, prospective clinical studies are required to determine whether T cell functional recovery correlates with therapeutic responses to PEG-IFN or functional cure. Consequently, applying HBV-specific T cell-associated biomarkers to develop reproducible, quantifiable, and generalizable clinical decision-making tools remains a significant challenge.
Among the currently available approaches for measuring HBV-specific T-cell responses, ELISpot represents one of the most widely adopted functional assays due to its relatively high sensitivity and operational simplicity[66,67]. Different research groups have established peptide libraries or assay workflows with varying antigen compositions and analytical strategies[68-71]. Our group recently reported one such ELISpot platform based on optimized HBV peptide libraries for routine detection of HBV-specific T-cell responses[15,72]. We conducted a baseline assessment of HBV-specific T cell function in 200 patients with CHB receiving PEG-IFN-α therapy. Preliminary analysis showed that patients with stronger baseline HBV-specific T cell responses tended to achieve higher treatment response rates and greater HBsAg clearance. This association was particularly pronounced in individuals with lower baseline HBsAg levels, suggesting a potential synergistic effect between viral antigen load and host immune capacity that jointly influences PEG-IFN treatment outcomes. Although the above results have not yet been formally published and still require further validation in large-scale, multicenter prospective studies, these real-world observations provide preliminary clinical evidence for HBV-specific T cells as immune-stratification and efficacy-prediction biomarkers, and further support the concept of incorporating host immune status into PEG-IFN precision treatment decision-making.
In the future, research on HBV-specific T cells will gradually shift from mechanistic exploration to clinical translation and precision application. On the one hand, based on standardized test platforms, research protocols, and evaluation criteria, international multicenter prospective clinical studies will be conducted to validate the stability, reproducibility, and clinical predictive value of HBV-specific T cell-associated parameters, thereby providing high-quality clinical evidence. On the other hand, immunomics technologies such as single-cell sequencing, spatial transcriptomics, and T-cell receptor clonal analysis will be used to analyze the dynamic changes in the phenotype, clonal expansion, and spatial tissue distribution characteristics of HBV-specific T cells during PEG-IFN therapy, further elucidating the immune reconstitution mechanism and identifying novel predictive biomarkers. Furthermore, as artificial intelligence and machine learning technologies advance, multimodal data integration and analysis will further enable the development of precise predictive models. Ultimately, we hope to establish a comprehensive HBV-specific T-cell immune-scoring system. By integrating virological, immunological, transcriptomic, and clinical characteristics, this scoring system will enable the quantitative assessment of patients’ immune status and therapeutic potential. Consequently, it will help identify patients who benefit from PEG-IFN therapy, providing more precise and intelligent support for individualized treatment strategies aimed at the functional cure of CHB.
The core issue in PEG-IFN therapy is not “whether to choose interferon”, but rather “whether the patient retains a reactivatable pool of HBV-specific T cells”. Driven by advancements in single-cell sequencing, multiparameter flow cytometry, and other immunomics techniques, the phenotypic, functional, and transcriptomic profiles of HBV-specific T cells are gradually emerging as novel biomarkers with the potential for clinical translation.
In the future, a comprehensive immune scoring system that integrates virological parameters with HBV-specific T cell-associated biomarkers will enable immune stratification of patients with chronic HBV. This will facilitate the precise screening of populations suitable for PEG-IFN therapy and improve functional cure rates. Ultimately, the future direction of precision treatment for CHB will shift from an experience-based decision-making model guided by virological markers to a personalized treatment model driven by immune status assessment.
Furthermore, more research on the functional cure of HBV is focusing on host immunity rather than the virus itself. In the future, the value of PEG-IFN, beyond its antiviral effects, will also lie in its role as an immune-remodeling tool that helps identify and activate HBV-specific T cells. With advances in immune surveillance technology, artificial intelligence prediction models, and novel immunotherapy strategies, precision treatment systems based on HBV-specific T cell status are expected to become an important foundational framework for the era of functional cure.
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