A P-value of less than 005 was considered to be significant The

A P-value of less than 0.05 was considered to be significant. The follow-up time was calculated as the interval between the date of surgery and intervention of the medical treatment, last follow up or recognition of HCC. Survival rates or failure rates were analyzed with the Kaplan–Meier method using the log–rank test to assess differences between curves. A P-value of less than 0.05 was check details considered to be significant. Statistical calculations were performed using the

JMP software package (release 10, SAS Institute, Cary, NC, USA). IN THE SEVEN follow-up liver biopsy sections (Table 2) available for histological examination, liver fibrosis in the hepatic lobules improved from F4 to F3 in four cases (cases 4–7: average, 268.5 ± 168.6 days; range, 42–431 days) (Fig. 2a). Improvements were not observed in the remaining three cases (cases 1–3: average, 312 ± 279.1 days; range, 24–581 days) (Fig. 2b). There were no statistical differences in the duration between the improvement cases and non-improvement

cases (P = 0.80). Conducting an evaluation was difficult because only a few specimens were available; however, no significant differences in clinical profiles were observed selleck screening library among the seven patients. In four of these cases (cases 4–7), the ratio significantly decreased from 19.5% to 8.2% (P < 0.05) (Fig. 2b), while the average AF in the remaining three cases (cases 1–3) increased from 8.0% to 13.1% (P = 0.15). The four cases of improved fibrosis were all Child–Pugh A, and one of the three cases that selleck kinase inhibitor showed no improvement was Child–Pugh B. In addition, AF before splenectomy was slightly higher in the improvement cases than in the non-improvement cases, while the CD4+/CD8+ ratio before splenectomy was lower in the improvement cases than in the non-improvement cases (P < 0.05). Histopathologically, CD4+ and CD8+ lymphocytes were mainly seen in the periportal area, and CD4+ lymphocytes were rarely seen in the hepatic lobules. The

epithelial cells, fibroblasts, monocytes and macrophages also produced TGF-β1.[4, 21, 26] However, we picked up and counted the TGF-β1 positive cells that were seen in the lymphocytes and found that these cells were distributed diffusely in the hepatic lobules and periportal area. The distribution pattern of Treg and granzyme B was the same as that of CD4+ and CD8+ lymphocytes, respectively. No significant differences were observed in the CD4+/CD8+ ratio (P = 0.21) in liver specimens, regardless of the association of HCC. The CD4+/CD8+ ratio (P < 0.05) and FOXP3/CD4+ ratio (P < 0.001) significantly increased with the progression of liver fibrosis (from F0 to F4). However, the granzyme B/CD8+ ratio was approximately constant, and was unrelated to the progression of liver fibrosis (P = 0.32). The number of TGF-β1 positive cells in livers with HCC was slightly higher than that in livers without (P = 0.

One prospective study [42] of 19 evaluable patients has shown tha

One prospective study [42] of 19 evaluable patients has shown that patients Imatinib with severe haemophilia A (FVIII < 1 IU dL−1) and a median age of 36 years, 80% of whom had target joints at study entry, treated with 25 IU kg−1 3 days a week, had a median of 0 bleeds in 6 months compared with a median of 21 bleeds while receiving on-demand treatment. The median (inter-quartile range) FVIII trough levels measured at 48 and 72 h in these patients were

6 (1–11) and 4 (0.5–6) IU dL−1, respectively. Further studies will be required to establish whether reducing FVIII usage to target lower trough levels would have resulted in a similar reduction in bleeds. Accordingly, it is important that studies performed on young children are not extrapolated to adults. Paediatric PK data on pdFIX are conspicuously absent in the literature. Data for rFIX are available, however, for the entire age range of patients with haemophilia

B [9,37–41,43]. There was no relationship between age and terminal half-life. In addition, there were only marginal trends with age for peak and trough levels, or for dose requirements to maintain a 1 IU dL−1 trough level, during prophylactic treatment [9]. These findings contrast with those for FVIII and it would be of interest to know whether they apply also to pdFIX. Knowledge of an individual patient’s FVIII half-life is likely Afatinib molecular weight to be useful when prescribing a prophylactic regimen. Patients with a long half-life may respond well to being treated every third day with dose adjustment having a useful effect on the trough level. Patients who undertake relatively limited activity and/or have a mild bleeding phenotype/pattern [44] are potentially more likely to be able to tolerate the more prolonged period of time with low factor levels associated with this type of regimen. Patients with shorter FVIII half-lives will probably respond better to adjusting the frequency of dosing. Patients, for example, who are having problems with break through bleeds or target joints despite routine prophylaxis or who want to undertake check details very active sports are

likely to benefit from a higher trough level. In both cases, this would be achieved more cost effectively by a period of daily dosing rather than increasing the dose on alternate days or three times a week, especially in patients with short half-lives. The benefit of frequently infused low-dose vs. intermittent high-dose FVIII treatment was recognized early [45,46]. Daily treatment, however, will not be a realistic option in many young children unless they have a central catheter. Understanding the effect of coagulation factor PK and dosing schedules also has important implications for treating patients where health care resources are limited. A low-dose daily prophylactic regimen may be possible in countries where standard regimens are too expensive.

One prospective study [42] of 19 evaluable patients has shown tha

One prospective study [42] of 19 evaluable patients has shown that patients INCB024360 mouse with severe haemophilia A (FVIII < 1 IU dL−1) and a median age of 36 years, 80% of whom had target joints at study entry, treated with 25 IU kg−1 3 days a week, had a median of 0 bleeds in 6 months compared with a median of 21 bleeds while receiving on-demand treatment. The median (inter-quartile range) FVIII trough levels measured at 48 and 72 h in these patients were

6 (1–11) and 4 (0.5–6) IU dL−1, respectively. Further studies will be required to establish whether reducing FVIII usage to target lower trough levels would have resulted in a similar reduction in bleeds. Accordingly, it is important that studies performed on young children are not extrapolated to adults. Paediatric PK data on pdFIX are conspicuously absent in the literature. Data for rFIX are available, however, for the entire age range of patients with haemophilia

B [9,37–41,43]. There was no relationship between age and terminal half-life. In addition, there were only marginal trends with age for peak and trough levels, or for dose requirements to maintain a 1 IU dL−1 trough level, during prophylactic treatment [9]. These findings contrast with those for FVIII and it would be of interest to know whether they apply also to pdFIX. Knowledge of an individual patient’s FVIII half-life is likely Selleck Everolimus to be useful when prescribing a prophylactic regimen. Patients with a long half-life may respond well to being treated every third day with dose adjustment having a useful effect on the trough level. Patients who undertake relatively limited activity and/or have a mild bleeding phenotype/pattern [44] are potentially more likely to be able to tolerate the more prolonged period of time with low factor levels associated with this type of regimen. Patients with shorter FVIII half-lives will probably respond better to adjusting the frequency of dosing. Patients, for example, who are having problems with break through bleeds or target joints despite routine prophylaxis or who want to undertake selleckchem very active sports are

likely to benefit from a higher trough level. In both cases, this would be achieved more cost effectively by a period of daily dosing rather than increasing the dose on alternate days or three times a week, especially in patients with short half-lives. The benefit of frequently infused low-dose vs. intermittent high-dose FVIII treatment was recognized early [45,46]. Daily treatment, however, will not be a realistic option in many young children unless they have a central catheter. Understanding the effect of coagulation factor PK and dosing schedules also has important implications for treating patients where health care resources are limited. A low-dose daily prophylactic regimen may be possible in countries where standard regimens are too expensive.

[59] Additionally, Ezzat et al reported that flavonoid (monoHER2

[59] Additionally, Ezzat et al. reported that flavonoid (monoHER2) prevented portal hypertension and hepatic injury including MMP-9 suppression.[60]

Nakamura et al. reported that sorafenib, which was a multiple tyrosine kinase receptor inhibitor targeting Ras/Raf kinase that also inhibits certain tyrosine kinases, reduced the severity of monoclotarine-induced SOS in rats through suppression of MMP-9 and c-Jun N-terminal kinase (JNK) activity.[61] Also, it was reported that sesame oil attenuated SOS by decreasing the recruitment of inflammatory cells including Kupffer cells and neutrophils, downregulating MMP-9 and upregulating tissue inhibitor of matrix metalloproteinase-1 expression.[62] All of these agents may be considered for possible clinical application in Alvelestat the near future. IN THIS REVIEW, the current recognition of hepatic injury

induced by L-OHP-based chemotherapy was summarized, particularly focusing on SOS. Even today, the pathophysiological mechanism of L-OHP-induced SOS remains unclear. Therefore, clinical disadvantage, evaluation system and targeted agents for preventing and reduction of SOS are yet to be fully elucidated. At the present stage, the algorithm to deepen understanding of the current status of SOS is shown in Figure 4. In future, further investigation should be conducted based on the molecular biology and pathology combined with drug targeting systems, selleck screening library which can provide some new ideas for the treatment of SOS. “
“Aim:  Effect of re-treatment for pegylated interferon (PEG-IFN) plus ribavirin was not fully evaluated. We examined the effects of re-treatment with PEG-IFN plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus who failed to achieve a sustained virological response (SVR) with

learn more combination therapy. Methods:  We examined 38 patients who were re-treated with PEG-IFN α2a plus ribavirin for more than 60 weeks, among whom 14 were non-responders and 24 were relapsers after previous treatment with PEG-IFN α2b plus ribavirin. IL28B genotyping was done in 21 patients. Results:  The overall SVR rate was 34%. Analysis of baseline characteristics showed that the relapsers had a significantly higher SVR rate than the non-responders (50.0%, 12/24 vs. 7.1%, 1/14, respectively, P = 0.012) The SVR rates of re-treated patients who had turned hepatitis C virus (HCV) RNA-negative at weeks 8, 12, 24, and 48 of the previous therapy were 67% (4/6), 67% (4/6), 29% (2/7), and 25% (1/4), respectively. Re-treatment achieved an SVR in five of 12 patients with IL28B major alleles and three of nine patients with IL28B minor alleles. During the re-treatment, patients with complete viral suppression at week-12 achieved a significantly higher SVR rate (P = 0.001).

binderanus is a nonindigenous species to North America This stud

binderanus is a nonindigenous species to North America. This study underscores the caution that should be applied to questions of diatom (and protistan) distributions in time and space. Clearly, the absence of evidence is not evidence click here of absence. “
“Blooms of the freshwater stalked diatom Didymosphenia geminata (Lyngb.) M. Schmidt in A. Schmidt typically occur in oligotrophic, unshaded streams and rivers. Observations that proliferations comprise primarily stalk material composed of extracellular polymeric substances (EPS) led us to ask whether or not the

production of excessive EPS is favored under nutrient-limited, high-light conditions. We conducted experiments in outdoor flumes colonized by D. geminata using water from the oligotrophic, D. geminata–affected Waitaki River, South Island, New Zealand, to determine the relationship between D. geminata stalk length, cell division rates, and light intensity under ambient and Selleckchem PLX4032 nutrient-enriched conditions. Stalk lengths were measured in situ, and cell division rates were estimated as the frequency of dividing cells (FDC). FDC responded positively

to increasing light intensity and to nutrient additions (N+P and P). Under ambient conditions, stalk length increased as light level increased except at low ambient light levels and temperature. Nutrient enrichment resulted in decreased stalk length and negative correlations with FDC, with this effect most evident under high light. Our results are consistent with the hypothesis that extensive stalk production in D. geminata occurs when cell division rates are nutrient limited and light levels are high. Thus, photosynthetically driven EPS production in the form of stalks, under nutrient-limited conditions, may explain

the development of very high biomass in this species in oligotrophic rivers. The responses of FDC and stalk length under nutrient-replete conditions are also consistent with occurrences of D. geminata as a nondominant component of mixed periphyton communities in high-nutrient streams. “
“In summer to autumn of 2008, a recently described thecate mixotrophic learn more dinoflagellate, Fragilidium duplocampanaeforme Nézan et Chomérat, occurred in Masan Bay, Korea, where it frequently contained bright-orange fluorescent inclusions. Using cultures of F. duplocampanaeforme isolated from Masan Bay, we investigated feeding, digestion, and prey specificity of this mixotroph. F. duplocampanaeforme fed exclusively on Dinophysis spp. when offered a variety of prey including dinoflagellates, a raphidophyte, a cryptophyte, a ciliate, and diatoms separately. In addition, F. duplocampanaeforme had allelopathic effects on other organisms, including cell immobilization/motility decrease (in Dinophysis acuminata, D. caudata, D. fortii, D.

binderanus is a nonindigenous species to North America This stud

binderanus is a nonindigenous species to North America. This study underscores the caution that should be applied to questions of diatom (and protistan) distributions in time and space. Clearly, the absence of evidence is not evidence selleck compound library of absence. “
“Blooms of the freshwater stalked diatom Didymosphenia geminata (Lyngb.) M. Schmidt in A. Schmidt typically occur in oligotrophic, unshaded streams and rivers. Observations that proliferations comprise primarily stalk material composed of extracellular polymeric substances (EPS) led us to ask whether or not the

production of excessive EPS is favored under nutrient-limited, high-light conditions. We conducted experiments in outdoor flumes colonized by D. geminata using water from the oligotrophic, D. geminata–affected Waitaki River, South Island, New Zealand, to determine the relationship between D. geminata stalk length, cell division rates, and light intensity under ambient and Akt inhibitor nutrient-enriched conditions. Stalk lengths were measured in situ, and cell division rates were estimated as the frequency of dividing cells (FDC). FDC responded positively

to increasing light intensity and to nutrient additions (N+P and P). Under ambient conditions, stalk length increased as light level increased except at low ambient light levels and temperature. Nutrient enrichment resulted in decreased stalk length and negative correlations with FDC, with this effect most evident under high light. Our results are consistent with the hypothesis that extensive stalk production in D. geminata occurs when cell division rates are nutrient limited and light levels are high. Thus, photosynthetically driven EPS production in the form of stalks, under nutrient-limited conditions, may explain

the development of very high biomass in this species in oligotrophic rivers. The responses of FDC and stalk length under nutrient-replete conditions are also consistent with occurrences of D. geminata as a nondominant component of mixed periphyton communities in high-nutrient streams. “
“In summer to autumn of 2008, a recently described thecate mixotrophic check details dinoflagellate, Fragilidium duplocampanaeforme Nézan et Chomérat, occurred in Masan Bay, Korea, where it frequently contained bright-orange fluorescent inclusions. Using cultures of F. duplocampanaeforme isolated from Masan Bay, we investigated feeding, digestion, and prey specificity of this mixotroph. F. duplocampanaeforme fed exclusively on Dinophysis spp. when offered a variety of prey including dinoflagellates, a raphidophyte, a cryptophyte, a ciliate, and diatoms separately. In addition, F. duplocampanaeforme had allelopathic effects on other organisms, including cell immobilization/motility decrease (in Dinophysis acuminata, D. caudata, D. fortii, D.

The duration of each step was determined experimentally using spe

The duration of each step was determined experimentally using specific controls (Supporting Fig. 2). The results clearly show that a decrease in HCVcc infection was only observed when EGCG was present during virus infection (Fig. 3A, second, third, fourth, and sixth bars in the bar-graph), and that there was no effect of EGCG if added as a pretreatment of the cells (Fig. 3A, first bar) or postinfection (Fig. 3A, fifth bar). These results suggest that EGCG inhibits an early step of the HCV life cycle, most likely the entry step. To confirm the effect of EGCG on HCV entry, HCVpp harboring E1 and E2 of different genotypes were produced. HCVpp

infectivity was reduced by approximately 10-fold with a concentration of 50 μM, confirming the effect of EGCG on HCV entry, whatever the genotype used (Fig. JAK activation 3B). However, PLX4032 cost some differences between genotypes could be observed at a lower EGCG concentration (5 μM). In contrast, vesicular stomatitis virus (VSV)pp entry was much less inhibited. These results suggest that the antiviral activity of EGCG is directed against HCV envelope glycoproteins and is genotype independent. Together, these data indicate that

EGCG inhibits HCV entry in a genotype-independent manner. Although the above data indicate that EGCG has a strong effect on HCV entry, we cannot exclude additional effects on other steps of the HCV life cycle. To analyze the effect of EGCG on HCV genome replication, Huh-7 cells were electroporated with in vitro transcribed assembly-defective JFH1-ΔE1/E2-Luc RNA, to bypass the entry step, and avoid any interference with late steps of the HCV life cycle. EGCG had no major effect on HCV replication, even after a longer period of treatment (96 hours postelectroporation) (Fig. 4A). In contrast, IFN-α, at 2 IU/mL, approximately twice the IC50 calculated for HCVcc in Huh-7 cells (1.15 IU/ml), 28 induced 1 log10 decrease of luciferase activity. To determine whether EGCG could have any effect on HCV assembly or secretion, intra- and extracellular core protein was quantified in infected

cells treated postinfection with 50 μM of EGCG for 70 hours. The amount this website of core in the culture supernatant reflects the quantity of secreted viral particles. A slight, but not significant (P = 0.10), decrease in intracellular core was observed in the presence of EGCG (Fig. 4B). This cannot be explained by a decrease in RNA replication, because it has been shown above that EGCG has no effect on HCV replication (Fig. 4A). However, the quantification of extracellular core showed a small, but not significant (P = 0.10), increase of secreted core in the presence of EGCG, as compared to the nontreated control (Fig. 4B), showing that EGCG does not impair viral secretion. Similar experiments were performed with JFH1-ΔE1/E2 to avoid reinfection of the cells and to quantify the levels of extracellular core resulting from cell lysis.

The duration of each step was determined experimentally using spe

The duration of each step was determined experimentally using specific controls (Supporting Fig. 2). The results clearly show that a decrease in HCVcc infection was only observed when EGCG was present during virus infection (Fig. 3A, second, third, fourth, and sixth bars in the bar-graph), and that there was no effect of EGCG if added as a pretreatment of the cells (Fig. 3A, first bar) or postinfection (Fig. 3A, fifth bar). These results suggest that EGCG inhibits an early step of the HCV life cycle, most likely the entry step. To confirm the effect of EGCG on HCV entry, HCVpp harboring E1 and E2 of different genotypes were produced. HCVpp

infectivity was reduced by approximately 10-fold with a concentration of 50 μM, confirming the effect of EGCG on HCV entry, whatever the genotype used (Fig. AZD2281 ic50 3B). However, NSC 683864 cell line some differences between genotypes could be observed at a lower EGCG concentration (5 μM). In contrast, vesicular stomatitis virus (VSV)pp entry was much less inhibited. These results suggest that the antiviral activity of EGCG is directed against HCV envelope glycoproteins and is genotype independent. Together, these data indicate that

EGCG inhibits HCV entry in a genotype-independent manner. Although the above data indicate that EGCG has a strong effect on HCV entry, we cannot exclude additional effects on other steps of the HCV life cycle. To analyze the effect of EGCG on HCV genome replication, Huh-7 cells were electroporated with in vitro transcribed assembly-defective JFH1-ΔE1/E2-Luc RNA, to bypass the entry step, and avoid any interference with late steps of the HCV life cycle. EGCG had no major effect on HCV replication, even after a longer period of treatment (96 hours postelectroporation) (Fig. 4A). In contrast, IFN-α, at 2 IU/mL, approximately twice the IC50 calculated for HCVcc in Huh-7 cells (1.15 IU/ml), 28 induced 1 log10 decrease of luciferase activity. To determine whether EGCG could have any effect on HCV assembly or secretion, intra- and extracellular core protein was quantified in infected

cells treated postinfection with 50 μM of EGCG for 70 hours. The amount selleck inhibitor of core in the culture supernatant reflects the quantity of secreted viral particles. A slight, but not significant (P = 0.10), decrease in intracellular core was observed in the presence of EGCG (Fig. 4B). This cannot be explained by a decrease in RNA replication, because it has been shown above that EGCG has no effect on HCV replication (Fig. 4A). However, the quantification of extracellular core showed a small, but not significant (P = 0.10), increase of secreted core in the presence of EGCG, as compared to the nontreated control (Fig. 4B), showing that EGCG does not impair viral secretion. Similar experiments were performed with JFH1-ΔE1/E2 to avoid reinfection of the cells and to quantify the levels of extracellular core resulting from cell lysis.

With the examples of aggressive mimicry we have considered so far

With the examples of aggressive mimicry we have considered so far, mind games and cognition have been

relevant primarily in the context of the prey’s response to the mimic’s signals. Yet it is the signal maker’s (i.e. the aggressive mimic’s) behaviour that has been most responsible for our interest in investigating aggressive selleck chemicals mimicry from a cognitive perspective. Before we shift our attention to the aggressive mimic’s behaviour, however, we need to indicate our stance towards the terms ‘mind’ and ‘cognition’. There are many reasons why cognition has a long history of being a notoriously controversial topic (Dennett, 1996). This includes a tradition of using ‘cognition’ and ‘mental’ more or less interchangeably, accompanied by a traditional notion that ‘mind’ is some sort of separate reality to which people have unique access (Descartes, 1637/1994). Minsky (1986, p. 287) famously expressed an alternative view by saying ‘minds are simply what brains do’. Instead of being a definition, this catchy phrase serves as a way of expressing a radical departure from Descartes’ view and an active decision not to propose a formal definition. ‘What brains do’ is accessible to scientific investigation and, if we gain a sufficiently detailed understanding

of what brains XL765 do, then the impression of needing a formal definition of ‘mind’ and the notion of there being a purely philosophical problem to address should recede into the background. Sometimes, ‘cognition’ is defined simply as ‘information processing’ (e.g. Shettleworth, 2009). However, when considering the interface between aggressive mimicry and animal cognition, we

prefer instead to emphasize representation. Representation has often been envisaged as a key attribute at the boundary between what does and does not qualify as cognitive (Damasio, 1994; Maunsell, 1995; Markman & Dietrich, 2000; but see Epstein, 1982). Vision is the context in which representation is especially often considered by psychologists, and this bias may tempt us to equate representation with something selleck kinase inhibitor like a picture in the animal’s head – a mental picture, or imagery (Neiworth & Rilling, 1987; Kosslyn, Ganis & Thompson, 2003; but see Pylyshyn, 2003a,b). Yet, we need a concept of representation that will be more basic and not unique to vision, and we do not really have to imply pictures in the animal’s head. We are happy to adopt Gallistel’s (1989) proposal that representation in the context of cognition functions in a way that is analogous to the way isomorphism functions in mathematics (e.g. the isomorphism between algebraic and graphical computations in geometry). In the case of representation, isomorphism refers to the formal correspondence between external reality (i.e. features of the environment) and the neural processes within an animal (Burge, 2010).

1% and 761% HBV-specific CD8 T cells in 458% of cases The spec

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. this website 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 Copanlisib in vivo 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. learn more 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.