The Declaration of Helsinki Principles was followed, and all participants gave written consent for participation in this study. The studies in animals were conducted in accordance with European Union

guidelines (86/609/CEE) and French National Chart guidelines, and protocols were approved by the local Ethics Committee for Animal Experimentation of Grenoble (ComEth). Ninety-four HLA-A*0201+ chronic HBV-infected patients and one resolved control were studied. HBV patients (Table 1) were classified as inactive carriers (HBeAg-negative, HBV-DNA <2,000 IU/mL, and consistently normal alanine aminotransferase [ALT] for at least 1 year), HBeAg-negative hepatitis, and HBeAg-positive hepatitis. Forty-eight patients were treated

(entecavir/tenofovir), and HBV-DNA was undetectable in 83% of these patients. Exclusion criteria included selleck chemicals llc human immunodeficiency virus/hepatitis C virus/hepatitis D virus coinfection, other liver diseases, and treatment with IFN-α or immunosuppressive agents. Serum HBs antigen was quantified using the Abbott Architect HBsAg QT assay http://www.selleckchem.com/products/VX-770.html (Abbott Diagnostics). Samples were also obtained from HLA-A*0201+ healthy donors. PBMCs were purified via Ficoll-Hypaque density-gradient centrifugation (Eurobio). Liver tissues, obtained from six HLA-A*0201+ HBV patients (Table 1), were processed to prepare liver-infiltrating lymphocytes (LILs). From all liver biopsies, we obtained 0.45 × 106 to 2.6 × 106 cells, among which 14.2%-58.2% were CD3+ T cells and 8.3%-43.3% were CD8+ T cells. The GEN2.2 pDC line was cultured as described.26 The HLA-A*0201+ hepatocyte line HepG2 was cultured in Dulbecco’s modified Eagle’s medium, 10% selleck fetal bovine serum, 50UI/ml penicillin/streptomycin (Invitrogen), 1 mM sodium pyruvate (Sigma). HepG22.15 (HepG2 transfected with HBV-DNA) was cultured in William’s E, 10% fetal

bovine serum, 50 IU/mL penicillin/streptomycin, 2 mM Glutamine (Invitrogen), 5 μg/mL insulin (Sigma) and 5.10−5 hydrocortisone hemisuccinate (Roche). All other cultures were performed in RPMI1640-Glutamax, 1% nonessential amino acids, 100 μg/mL gentamycin, 10% fetal bovine serum (Invitrogen), and 1 mM sodium pyruvate (Sigma). T2 and K562 lines were purchased from American Type Culture Collection (LGC Standards). We used the following HLA-A*0201-restricted peptides (NeoMPS) and corresponding HLA-A*0201 tetramers (Beckman): HBc18-27 (FLPSDFFPSV; core), HBs335-343 (WLSLLVPFV; surface), pol575-583 (FLLSLGIHL; polymerase), and FluM158-66 (GILGFVFTL; influenza matrix). The pDC line was loaded with peptides as described.26 PBMCs or LILs were cocultured with peptide-loaded pDCs at a 1:10 ratio and restimulated weekly in presence of 200 IU/mL IL-2 (Proleukine, Chiron). In some experiments, PBMCs were directly stimulated with the peptide (1-10 μM final) for 10 days.

[184-186] In cases where the HBV DNA levels during lamivudine therapy remained <2.6 log copies/mL, HBV DNA continued negative after switching to entecavir, and entecavir-resistant virus was not detected. On the other hand, when the HBV DNA levels is ≥2.6 log copies/mL at the time of switching, entecavir-resistant HBV may appear irrespective of whether lamivudine-resistant virus

was already present. Concerning problems with safety, almost no adverse reactions of clinical importance XAV-939 nmr were reported. Points to keep in mind are that entecavir is not suitable for long term continuous therapy for women desiring to bear children due to the risk of teratogenesis, GSK126 and the safety of long term administration has not been established. Recommendations Favourable results are obtained with entecavir in patients naïve to NAs, with

a low incidence of resistant virus, currently making entecavir the first-choice NA. Switching to entecavir is recommended in patients in whom the HBV DNA negative conversion occurs with lamivudine therapy. It has been reported that if lamivudine-resistant HBV appears and the viral load increases, onset of hepatitis is likely; furthermore, in some cases the hepatitis may become severe.[157, 187] Accordingly, treatment with an antiviral agent is required if lamivudine-resistant HBV appears. IFN, adefovir selleck screening library and entecavir have been confirmed effective against lamivudine-resistant HBV, and are currently approved for Japanese medical insurance. Although IFN can be used to a certain extent to treat hepatitis associated with lamivudine-resistant HBV, there are problems with adverse reactions and a limited treatment duration.[188,

189] On the other hand, adefovir has good long term efficacy against lamivudine-resistant HBV, with mild adverse reactions and suitable for long term therapy, so currently adefovir is recommended. Rather than switch from lamivudine to adefovir, lamivudine and adefovir in combination provides a stronger antiviral effect.[190] The long term effect of lamivudine+adefovir combination therapy against lamivudine-resistant HBV has been reported as an HBV DNA negative conversion rate (<2.6 log copies/mL) using the Amplicor testing of 56–82% at 1 year, 74–84% at 2 years, 81–86% at 3 years, 80–92% at 4 years, and 85–86% at 5 years.[158, 159, 161, 164, 165, 167] Reported factors relating to the antiviral effect of lamivudine+adefovir combination therapy include DNA load (low value), albumin level (low), ALT level (high), HBeAg (negative), and HBV DNA negative conversion during lamivudine therapy.[159, 165, 166, 168] Reported ALT normalization rates were 67–81% at 1 year, 75–83% at 2 years, 80–92% at 3 years, 82–90% at 4 years, and 85% at 5 years.

The survival rate is relatively favorable at 53% with medical therapy of acute infections, but only 16% in cases of acute exacerbation of the carrier state.[285] The prognosis is particularly poor in cases of fulminant hepatitis B occurring in patients with HBV reactivation.[288] Differentiation between acute infection and acute on chronic infection can be difficult,

even selleck chemicals llc using HBV markers from before and after the onset of infection. For the etiological diagnosis of fulminant hepatitis B, we measure HBsAg, anti-HBs antibody, anti-IgM-HBc antibody, anti-HBc antibody, and HBV DNA levels. We can differentiate between acute infection and acute exacerbation of the carrier state through the presence of HBsAg prior to disease onset, and positive conversion of anti-HBs antibody during the disease course. If these markers are indeterminate, the anti-IgM-HBc antibody and anti-HBc antibody titers at the time of disease onset may be considered. In general, in acute infections anti-IgM-HBc antibody are positive with a high titer, whereas HBc antibody have a low titer. In carriers, the anti-IgM-HBc antibody titer is low, and the anti-HBc antibody titer is high. At present, anti-IgM-HBc antibody

titers are usually measured using the CLIA (chemiluminescent immunoassay) method, with a cut-off titer of 10.0 for differentiation between acute infection and acute on chronic infection.[289] Determination of anti-HBc antibody titers using the CLIA method is becoming more common, although this

has actually made differentiation between acute www.selleckchem.com/products/chir-99021-ct99021-hcl.html infection and acute on chronic infection more difficult in comparison with the earlier RIA (radioimmunoassay) and EIA (enzyme immunoassay) 1:200 dilution methods. HBV reactivation should be suspected in patients on immunosuppressive therapy or chemotherapy before or at the time of disease onset. A variety of HBV variants have been reported in association with fulminant hepatitis B, and preferably the HBV genotype, and the presence of precore and core promoter mutations should be determined. The B1/Bj genotype is common in fulminant hepatitis associated with acute infections,[5] and high incidences of core check details promoter (A1762T/G1764A) and precore (G1896A/G1899A) mutations have also been reported.[5, 60, 290-293] An association has also been reported between preS2 variants, S antigen variants, and fulminant hepatitis B.[294-296] On the other hand, no specific variants have been identified in HBV carriers developing acute exacerbation. Recommendation HBsAg, anti-HBs antibody, anti-IgM-HBc antibody, anti-HBc antibody, and HBV DNA levels should be determined in patients with fulminant hepatitis B to make the etiological diagnosis. Determination of HBV genotype and the presence of precore and core promoter mutations is also desirable. In general, acute hepatitis B is a condition that resolves naturally, with no need for treatment.

The survival rate is relatively favorable at 53% with medical therapy of acute infections, but only 16% in cases of acute exacerbation of the carrier state.[285] The prognosis is particularly poor in cases of fulminant hepatitis B occurring in patients with HBV reactivation.[288] Differentiation between acute infection and acute on chronic infection can be difficult,

even Sirolimus using HBV markers from before and after the onset of infection. For the etiological diagnosis of fulminant hepatitis B, we measure HBsAg, anti-HBs antibody, anti-IgM-HBc antibody, anti-HBc antibody, and HBV DNA levels. We can differentiate between acute infection and acute exacerbation of the carrier state through the presence of HBsAg prior to disease onset, and positive conversion of anti-HBs antibody during the disease course. If these markers are indeterminate, the anti-IgM-HBc antibody and anti-HBc antibody titers at the time of disease onset may be considered. In general, in acute infections anti-IgM-HBc antibody are positive with a high titer, whereas HBc antibody have a low titer. In carriers, the anti-IgM-HBc antibody titer is low, and the anti-HBc antibody titer is high. At present, anti-IgM-HBc antibody

titers are usually measured using the CLIA (chemiluminescent immunoassay) method, with a cut-off titer of 10.0 for differentiation between acute infection and acute on chronic infection.[289] Determination of anti-HBc antibody titers using the CLIA method is becoming more common, although this

has actually made differentiation between acute Daporinad chemical structure infection and acute on chronic infection more difficult in comparison with the earlier RIA (radioimmunoassay) and EIA (enzyme immunoassay) 1:200 dilution methods. HBV reactivation should be suspected in patients on immunosuppressive therapy or chemotherapy before or at the time of disease onset. A variety of HBV variants have been reported in association with fulminant hepatitis B, and preferably the HBV genotype, and the presence of precore and core promoter mutations should be determined. The B1/Bj genotype is common in fulminant hepatitis associated with acute infections,[5] and high incidences of core click here promoter (A1762T/G1764A) and precore (G1896A/G1899A) mutations have also been reported.[5, 60, 290-293] An association has also been reported between preS2 variants, S antigen variants, and fulminant hepatitis B.[294-296] On the other hand, no specific variants have been identified in HBV carriers developing acute exacerbation. Recommendation HBsAg, anti-HBs antibody, anti-IgM-HBc antibody, anti-HBc antibody, and HBV DNA levels should be determined in patients with fulminant hepatitis B to make the etiological diagnosis. Determination of HBV genotype and the presence of precore and core promoter mutations is also desirable. In general, acute hepatitis B is a condition that resolves naturally, with no need for treatment.

The design and power of this study is a much needed quantum leap in the quality of research that evaluates interventions in BE: it is sufficiently powered to allow use of the robust primary outcome measure of development of high-grade dysplasia or EA. The first major data from the AspECT study will be available in 2012. Already, safety monitoring indicates that aspirin therapy combined with PPI has a low rate of serious adverse events (Prof J Jankowski, personal communication). If the chemopreventive effect of low-dose aspirin predicted by

epidemiologic studies79,80 is confirmed, this is likely to become a widely recommended therapy for reduction of the cancer risk in BE patients (Fig. 2). Low-dose aspirin and NSAIDs are not the only plausible candidates for chemoprevention of EA. Evidence of a chemopreventive this website effect of statins, suggested by cell biology studies,80 has also been found by a recent epidemiologic study.81 Several other options HIF inhibitor have also been proposed as worthy of investigation.80 Observational studies will need to give a consistently promising signal on the possible chemopreventive properties of a novel option before a definitive prospective, randomized intervention study is considered, because of the huge effort involved. It is most unlikely that positive results from chemopreventive studies will alter recommendations for endoscopic surveillance in the

near future, but in due course, such therapy might allow increases of intervals between surveillance endoscopies and so positively influence cost-effectiveness. A meta-analysis has found that the risk for EA was 1.63 per 1000 patients-years in 6847 patients treated selleck products in uncontrolled studies with a range of mucosa-ablative therapies.84 This contrasts with

an estimated risk of 5.98 per 1000 patient-years, determined in other studies of BE patients free of dysplasia who did not have ablative therapy.84 This impressive apparent risk reduction is potentially influenced by several confounders, but makes biological sense. The pros and cons of taking this aggressive approach in patients free of dysplasia are well reviewed by Sharma and colleagues85 who emphasize the need to weigh the risks and not insignificant cost of this intervention against the relatively low risk for EA in BE patients free of dysplasia.14 The number needed to treat to prevent one cancer, let alone one death from cancer is high, so the potential to harm is also high. In expert hands, the risks of ablation are relatively small. If mucosal ablation came to be widely practiced outside expert centers, its risks are likely to be greater in that setting. More randomized comparisons are needed on the long-term efficacy of the several options for ablation of metaplastic mucosa. Currently, mucosal ablation in patients with non-dysplastic BE should only be done within well-designed clinical trials.

The design and power of this study is a much needed quantum leap in the quality of research that evaluates interventions in BE: it is sufficiently powered to allow use of the robust primary outcome measure of development of high-grade dysplasia or EA. The first major data from the AspECT study will be available in 2012. Already, safety monitoring indicates that aspirin therapy combined with PPI has a low rate of serious adverse events (Prof J Jankowski, personal communication). If the chemopreventive effect of low-dose aspirin predicted by

epidemiologic studies79,80 is confirmed, this is likely to become a widely recommended therapy for reduction of the cancer risk in BE patients (Fig. 2). Low-dose aspirin and NSAIDs are not the only plausible candidates for chemoprevention of EA. Evidence of a chemopreventive GSK2118436 price effect of statins, suggested by cell biology studies,80 has also been found by a recent epidemiologic study.81 Several other options X-396 chemical structure have also been proposed as worthy of investigation.80 Observational studies will need to give a consistently promising signal on the possible chemopreventive properties of a novel option before a definitive prospective, randomized intervention study is considered, because of the huge effort involved. It is most unlikely that positive results from chemopreventive studies will alter recommendations for endoscopic surveillance in the

near future, but in due course, such therapy might allow increases of intervals between surveillance endoscopies and so positively influence cost-effectiveness. A meta-analysis has found that the risk for EA was 1.63 per 1000 patients-years in 6847 patients treated selleck inhibitor in uncontrolled studies with a range of mucosa-ablative therapies.84 This contrasts with

an estimated risk of 5.98 per 1000 patient-years, determined in other studies of BE patients free of dysplasia who did not have ablative therapy.84 This impressive apparent risk reduction is potentially influenced by several confounders, but makes biological sense. The pros and cons of taking this aggressive approach in patients free of dysplasia are well reviewed by Sharma and colleagues85 who emphasize the need to weigh the risks and not insignificant cost of this intervention against the relatively low risk for EA in BE patients free of dysplasia.14 The number needed to treat to prevent one cancer, let alone one death from cancer is high, so the potential to harm is also high. In expert hands, the risks of ablation are relatively small. If mucosal ablation came to be widely practiced outside expert centers, its risks are likely to be greater in that setting. More randomized comparisons are needed on the long-term efficacy of the several options for ablation of metaplastic mucosa. Currently, mucosal ablation in patients with non-dysplastic BE should only be done within well-designed clinical trials.

60). PPH was observed in 7/24 (29%) deliveries in women known prepregnancy to have VWD. The unadjusted odds for VWD as a risk factor for PPH in this group was significantly greater than the control group (OR 2.78 (95% CI 1.03–7.49) P = 0.043) and remained significant after adjusting for other significant risk factors (OR 3.41 (95% CI 1.07–10.9) P = 0.038). VWD in itself may not be a significant risk factor for PPH, however, women known to have VWD predelivery may represent an at risk sub-group. “
“The development of inhibitors usually renders hemophilia A patients refractory to factor VIII replacement therapy. The inhibitor bypassing agents

activated PCC and recombinant activated factor VII (rFVIIa) are highly effective for Tanespimycin treating bleeding and for providing surgical hemostasis but responses SB203580 order are not entirely predictable, and they cannot be monitored by conventional laboratory assays. Their high cost may make them relatively inaccessible in developing countries. Eradication of inhibitors by induction of immune tolerance (ITI) is achievable in most patients but there is no consensus on optimal regimens. Promising new agents for inhibitor treatment are under development, including recombinant porcine factor VIII and altered rFVIIa molecules with enhanced potency or improved pharmacokinetics. Factor IX inhibitors in hemophilia B patients occur rarely but

they are even more problematic, as they may be associated with severe allergic reactions and they respond poorly to ITI. “
“Summary.  Previous data have shown an inter-individual difference in the thrombin selleckchem generating capacity in vitro as well as phenotypic bleeding pattern among patients with severe haemophilia A (FVIII:C activity below 1%). The reason for this is not

known. In addition, there are no reports on how thrombin generation may correlate between siblings. In this study, we evaluated and compared thrombin generation in vitro using plasma samples in the presence of by-passing agents (FEIBA® and NovoSeven®) in 21 unrelated brother pairs with and without inhibitors enrolled in the Malmö International Brother Study (MIBS). Mean maximum thrombin formation in patients with a current inhibitor titer was 182.0 ± 52.8 mmol mL−1 (FEIBA®) and 130.7 ± 54.9 mmol mL−1 (rFVIIa), respectively, and somewhat higher in those without inhibitors, 222.7 ±85.5 mmol mL−1 (FEIBA®) and 142.8 ±53.6mmol mL−1 (rFVIIa) (P = 0.16 and 0.29). The variance regarding the maximum thrombin production within a family was significantly lower compared with the thrombin production between families (P < 0.001 for both FEIBA® and NovoSeven®). Our data indicate that genetically determined factors, other than the FVIII:C activity seems to influence the phenotypic variation in thrombin formation in the presence of by-passing agents. The nature of these determinants remains to be identified.

60). PPH was observed in 7/24 (29%) deliveries in women known prepregnancy to have VWD. The unadjusted odds for VWD as a risk factor for PPH in this group was significantly greater than the control group (OR 2.78 (95% CI 1.03–7.49) P = 0.043) and remained significant after adjusting for other significant risk factors (OR 3.41 (95% CI 1.07–10.9) P = 0.038). VWD in itself may not be a significant risk factor for PPH, however, women known to have VWD predelivery may represent an at risk sub-group. “
“The development of inhibitors usually renders hemophilia A patients refractory to factor VIII replacement therapy. The inhibitor bypassing agents

activated PCC and recombinant activated factor VII (rFVIIa) are highly effective for Sorafenib datasheet treating bleeding and for providing surgical hemostasis but responses Sunitinib clinical trial are not entirely predictable, and they cannot be monitored by conventional laboratory assays. Their high cost may make them relatively inaccessible in developing countries. Eradication of inhibitors by induction of immune tolerance (ITI) is achievable in most patients but there is no consensus on optimal regimens. Promising new agents for inhibitor treatment are under development, including recombinant porcine factor VIII and altered rFVIIa molecules with enhanced potency or improved pharmacokinetics. Factor IX inhibitors in hemophilia B patients occur rarely but

they are even more problematic, as they may be associated with severe allergic reactions and they respond poorly to ITI. “
“Summary.  Previous data have shown an inter-individual difference in the thrombin check details generating capacity in vitro as well as phenotypic bleeding pattern among patients with severe haemophilia A (FVIII:C activity below 1%). The reason for this is not

known. In addition, there are no reports on how thrombin generation may correlate between siblings. In this study, we evaluated and compared thrombin generation in vitro using plasma samples in the presence of by-passing agents (FEIBA® and NovoSeven®) in 21 unrelated brother pairs with and without inhibitors enrolled in the Malmö International Brother Study (MIBS). Mean maximum thrombin formation in patients with a current inhibitor titer was 182.0 ± 52.8 mmol mL−1 (FEIBA®) and 130.7 ± 54.9 mmol mL−1 (rFVIIa), respectively, and somewhat higher in those without inhibitors, 222.7 ±85.5 mmol mL−1 (FEIBA®) and 142.8 ±53.6mmol mL−1 (rFVIIa) (P = 0.16 and 0.29). The variance regarding the maximum thrombin production within a family was significantly lower compared with the thrombin production between families (P < 0.001 for both FEIBA® and NovoSeven®). Our data indicate that genetically determined factors, other than the FVIII:C activity seems to influence the phenotypic variation in thrombin formation in the presence of by-passing agents. The nature of these determinants remains to be identified.

Among the components of the VEGF signaling pathway, the three VEGF receptors and their coreceptor Nrp2 were shown to be strongly down-regulated in LSEC in vitro. Wnt-2, previously identified by us as a positive regulator of VegfR2, and its receptors were also drastically decreased upon culture.

Thus, defective Wnt signaling may enhance and synergize with defective Vegf receptor activity in cultured LSEC in a vicious circle. Furthermore, Sirolimus mw primary Vegf receptor deficiency in cultured LSEC may explain impaired LSEC proliferation in culture despite the presence of high concentrations of Vegf in LSEC culture media. As of now, a unique blood vascular EC-specific master regulator, as is Prox1 for lymphatic EC, has not be identified and specific gene expression in different blood vascular EC is thought to be mediated by combinations of otherwise

nonspecific transcriptional regulators. The LSEC-specific transcription factors Tfec, Gata4, Maf, and Lmo3 identified here may well represent such an EC subtype-specific combination of transcriptional regulators. Gata4 has been shown to be important in development of the liver and of cardiac myocytes. Although Gata2, 3, and 6 are expressed in different EC and transcriptionally target EC-specific genes such as vWF, VCAM-1, and Tie-2,22 Gata4 is not generally expressed in blood vascular selleck compound EC. Interestingly, endothelial Gata4 expression specifically induces the formation of the heart valves, a site where the sinusoidal endothelial marker proteins Stabilin-1 and -2 are also expressed.23 Thus, specific overexpression of Gata4 in LSEC versus LMEC-associated overexpression of Gata2, 3, and 5 renders Gata4 an attractive candidate for at least coregulating LSEC-specific gene transcription. Tfec, a bHLH transcription factor of the Mitf family contributes to IL-4-induced macrophage activation, suggesting a possible role in regulation of immune system processes in selleck LSEC; interestingly, the Mitf-family member Tfeb is involved in placental vascularization.24 Although the proto-oncogene c-Maf has been

shown to induce the angiogenic surface aminopeptidase N/CD13 in EC in vitro, our microarray analysis showed that CD13 expression was decreased in LSEC versus, LMEC indicating that MAF may target different genes in LSEC.25 Because Lmo family members have been shown to interact with Gata and bHLH transcription factors,26 Lmo3 could be involved in the regulation of LSEC-specific gene expression, possibly by interaction with Gata4 and/or Tfec. In this study we furthermore show that the LSEC-specific differentiation program comprises a novel, highly conserved 278 aa type-1 transmembrane protein selectively expressed in liver endothelium that was named liver endothelial differentiation-associated protein (Leda)-1.

1% and 76.1% HBV-specific CD8 T cells in 45.8% of cases. The specific T cells from the “responder” group secreted interferon-γ, expressed CD107 upon restimulation,

and efficiently lysed HBV antigen-expressing hepatocytes. Circulating hepatitis B e antigen (HBeAg) was found to distinguish the group of patients not responding to the pDC stimulation. The therapeutic efficacy of the pDC vaccine was evaluated in immunodeficient NOD-SCID β2m−/− mice reconstituted with HBV patients’ PBMCs and xenotransplanted with human HBV-transfected hepatocytes. AZD0530 order Vaccination of Hepato–HuPBL mice with the HBc/HBs peptide–loaded pDCs elicited HBV-specific T cells able to specifically lyse the transfected hepatocytes and reduce the systemic viral load. Conclusion: pDCs loaded MK0683 solubility dmso with HBV–derived peptides can elicit functional virus-specific T cells. HBeAg appears to be critical in determining the outcome of immunotherapies in chronic HBV patients. A pDC-based immunotherapeutic approach could be of interest in attempts to restore functional antiviral

immunity, which is critical for the control of the virus in chronic HBV patients. (HEPATOLOGY 2012;56:1706–1718) Despite increasing awareness and extensive vaccination campaigns, chronic hepatitis B infection remains a global health problem.1 Antiviral drugs such as interferon (IFN)-α and nucleoside/nucleotide analogues efficiently suppress viral replication and reduce hepatic symptoms. However, viral covalently closed circular DNA often persists in hepatocytes and, combined with viral escape mechanisms,2 may cause disease relapse. Unfortunately, antiviral therapies are not yet capable of definitive virus eradication. Interestingly, the pathophysiology of hepatitis B virus (HBV) appears to be closely related to host immunity.3, 4 Patients who manage to clear the

virus elicit vigorous and efficient multispecific T cell responses. In contrast, patients who evolve toward chronic infection mount only weak and inappropriate immune responses.5–7 Immune responses are directed toward epitopes located within the major HBV proteins:8 nucleoscapsid HBc and HBs. click here In particular, HBc-specific cytotoxic T cells play a critical role in controlling the viral infectious cycle through their ability to lyse persistently infected hepatocytes. Their activity has been shown to significantly contribute to virus clearance and resolution of infection.6, 9, 10 Resolution of chronic HBV infection has been achieved in patients after adoptive transfer of immunity to HBc antigen.11 Another approach, involving reversing T cell exhaustion, such as blocking the PD-1 pathway,12 could also restore functional antiviral immunity. Numerous immunotherapeutic approaches have been developed in attempts to restore functional anti-HBV immunity.