Prevalence of Children Vaccinated against Viral Hepatitis B in Brazzaville

Introduction: Viral hepatitis B (VHL) is a public health problem, particularly in sub-Sahara Africa. The aim of this study was to assess vaccination coverage against HBV in children in Brazzaville. Patients and Methods: This was a cross-sectional analytical study conducted in Brazzaville health centres from January to September 2019. It involved children aged between six months and six years who received a vaccination against HBV. Sampling was exhaustive and based on stratified sampling. Results: The overall prevalence of children vaccinated against HBV in Brazzaville was 96.2%. It was insufficient in the Talangai health district (79%). The pentavalent vaccine was administered to 97.7% of children, 85% of whom had received all three doses. The reasons for incomplete vaccination were parents’ ignorance of HVB (85.6%) and of vaccination (14.3%). Conclusion: Although the prevalence of vaccinated children is high in Brazzaville, it is still insufficient in some health districts, particularly Talangai, because parents are unaware of the disease and of vaccination. Pentavalent is the only vaccine available in the national vaccination programme, which is why an effective national vaccination policy needs to be put in place. .

Perception of Medical Students towards Hepatitis B Virus Infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria

Background: Prevention is one of the safe schemes against the high prevalence of viral Hepatitis. Negative perceptions or perceptions about the risks of hepatitis B among medical students and health care workers may influence the behavioral pattern and adoption of preventive measures against the virus and can affect the uptake of the Hepatitis B vaccine. This study assesses the perception of medical students towards Hepatitis B virus infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria. Methods: This was a descriptive cross-sectional study done in August 2021 among 236 clinical medical students using a multistage sampling technique. Data was collected using an interviewer-administered structured questionnaire and analysed using the IBM SPSS 28 (Statistical Package for the Social Sciences). Ethical approval was granted by Bingham University Teaching Hospital, Ethics Committee, Jos, Plateau State. Results: Two-thirds of respondents were of the opinion that they are at risk of contracting HBV. Half were of the opinion that the risk is very much while a third believed the risk is moderate. Among those who think they are not at risk of contracting HBV, the majority felt so because they are vaccinated while 10.3% believe that they are safe. 43.2% of respondents think that HBV Vaccine is very effective in preventing HBV infection while 39.8% think it is slightly effective, and 7.6% think it is not effective. Almost all respondents, 99.2% are of the opinion that HBV Vaccination is important for students while 0.8% think it is not important. The majority of the respondents at 95.8% were willing to be screened for HBV. The majority (85.6%) of respondents are willing to pay for HBV Vaccine as against 14.4% of respondents who are not willing to pay. Conclusion: Summarily, 21 (8.9%) of the students had a negative perception of Hepatitis B Vaccination, and 215 (91.1%) had a positive perception of Hepatitis B Vaccination. Perception-sustaining events like seminars, workshops, road shows, and campaigns should be organized among students and health workers.

The Association of Hepatitis B Vaccine Supply Policy with Timing of Receipt of the First Dose of Hepatitis B Vaccination

An estimated 800,000 - 1.4 million persons in the US have chronic hepatitis B virus (HBV) infection. The risk for chronic infection is greatest among young children;approximately 90% of infants will remain chronically infected with HBV. Approximately 25% of those who become chronically infected during childhood die prematurely from cirrhosis or liver cancer. Hepatitis B vaccination is the most effective measure to prevent HBV infection and its consequences. In 2006, 29 US states had Hepatitis B Vaccine Supply (HBVS) policy which either supplies hepatitis B vaccine at no cost to all providers for all children or provides hepatitis B vaccine to delivery hospitals-only free of charge for all infants;other 21 US states and the District of Columbia did not have. 17,636 infants born in 2006 obtained from 2007-2009 National Immunization Survey (NIS) were analyzed with survival analysis procedures of Kaplan-Meier estimate and Cox proportional hazards model for complex sample survey to evaluate the association between state HBVS policy and the timing of infant age in days to receipt of hepatitis B vaccination. State HBVS policy is associated with infant age in days from birth to receipt of the first dose of hepatitis B vaccine (P < 0.01), and to completion of the 3-dose hepatitis B vaccine series (P < 0.01). Receipt of the first dose of hepatitis B vaccine occurred 31% earlier among infants residing in states with HBVS policy than among infants residing in states without (adjusted hazards ratio 1.31, 95%CI (1.23, 1.39)). Completion of the 3-dose hepatitis B vaccine series were 12% sooner among infants living in states with HBVS policy than among infants living in states without (adjusted hazards ratio 1.12, 95%CI (1.06, 1.18)). State HBVS policy may help overcome barriers to timely delivery of hepatitis B vaccines to infants.

A 12-year cohort study on the efficacy of plasmaderived hepatitis B vaccine in rural newborns

AIM To understand the anti-HBs persistenceand the long-term preventive efficacy in ruralnewborns after vaccination with plasma-derivedhepatitis B vaccine.METHODS In the time of expanded program onimmunization(EPI),the newborns werevaccinated with 10μg×3 doses of hepatitis Bvaccine and 762 newborns who were HBsAgnegative after primary immunization wereselected for cohort observation from 1986 to1998.Their serum samples were detectedqualitatively and quantitatively for hepatitis Binfecting markers,including HBsAg,anti-HBsand anti-HBc by SPRIA Kits.The annual HBsAgpositive conversion rate was counted by life-table method.RESULTS①The anti-HBs positive rate was94.44% for the babies born to HBsAg negativemothers and 84.21% for those born to HBsAgpositive mothers in the 1st year afterimmunization,and dropped to 51.31% and52.50% in the 12th year respectively.GMT valuewas dropped from 31.62 to 3.13 and 23.99 to 3.65in the 2nd to the 12th year respectively.Therewas a marked drop in GMT at the 3rd to the 5thyear,and in anti-HBs positive rate at the 9th tothe 10th year.②In the period of 12 yearsobservation,the person-year HBsAg positive conversion rates were 0.12%(5/4150.0)innewborns born to HBsAg negative mothers and0.20%(1/508.0)in those born to HBsAgpositive mothers,and none of the HBsAgpositive converted children became HBsAgchronic carriers.Compared with the baselinebefore immunization,the protective rates were97.19% and 95.32% respectively.CONCLUSION The protective efficacy ofplasma-derived hepatitis B vaccine persisted atleast 12 years,and a booster dose seems notnecessary within at least 12 years after theprimary three-doses immunization to newbornsborn to HBsAg negative mothers.

Phase Ⅱb trial of in vivo electroporation mediated dualplasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy

AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.

Hepatitis B virus subgenotype F3 reactivation with vaccine escape mutations:A case report and review of the literature

Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus(HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R, P120 Q, and Q129 P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.

Insights into induction of the immune response by the hepatitis B vaccine

After more than four decades of hepatitis B virus(HBV)vaccine implementation,its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved.Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth.All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications.However,there are still many drawbacks to overcome.The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization.Additionally,the current most widely used second-generation vaccines do not induce protective immunity in 5%to 10%of the population,particularly in people over 40-years-old,obese(body mass index>25 kg/m2),heavy smokers,and patients undergoing dialysis or infection with human immunodeficiency virus.Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance,particularly in difficult settings.These advances re-launch the expectations of achieving the World Health Organization’s objective of completing hepatitis control by 2030.

THREE－YEAR FOLLOW－UP AFTER A SINGLE BOOSTER DOSE OF VACCINE IN THE NONRESPONDERS AND HYPORESPONDERS TO HEPATITIS B VACCINE

Immuuoresponsiveness of revacclnation in nonresponders and hyporesponders to hepatitis B vaccine was evaluated.10 nonresponders and kyporesponders as well as 18 normal responders to the primary vaccination were offered a 10μg dose or blood-derived vaccine in May 1989,three years after a 3-dose primary vaccine schedule,and were rollowed up and checked at 2,6,12 and 36 months after the booster dose.The results showed that Anti-HBs titre increased in both poor and normal responders,but the antibody level in nonresponders and hyporesponders was lower and the duration of persistence was much shorter,while the antibody GMT in normal responders remained above protective level at 36 months arter revaccination.Thererore,it is difficult to say,according to the data,that revaccination can satisfactorily boost anti-HBs level in the poor responders.

Immunogenicity of recombinant hepatitis B vaccine in treatment-nave and treatment-experienced chronic hepatitis C patients: The effect of pegylated interferon plus ribavirin treatment

瞄准：为了回顾地评估导致种痘的 anti-HBs seroconversion，评价在处理天真并且处理富有经验长期的丙肝(CHC ) 病人。另外， seroconversion 加 ribavirin (肋骨) 在 pegylated 干扰素(木钉) 期间在 CHC 评估病人有希望地评估治疗。方法：七十个处理天真的 CHC 病人(组 A ) ，加肋骨治疗 CHC 病人(组 B ) 的 22 持续 virological responders-SVR 追随者干扰素(IFN ) 和 121 个健康题目(组 C ) 被参予了一样的 HBV 种痘时间表(20 microg， 0-1-6 瞬间) 。如果 anti-HBs 层次在在跟随疫苗的第三剂量的 3 瞬间以内的 10 mIU/mL 上面， Seroconversion 被考虑。而且，我们有希望地选择了 30 个非肝脏硬化症的 CHC 病人并且为使随机化的一样的疫苗的时间表的功效评估了他们他们在二个组：Group-1， 15 个 CHC 病人加肋骨治疗和 Group-2 与木钉的开始同时收到了疫苗的第一剂量，没有伴随物治疗， 15 个病人收到了一样的种痘时间表。anti-HBs 的决心在瞬间 1， 2，和 7 点被执行。数据的统计分析基于 ANOVA 学生的 t 测试和 chi 平方分析(P 【 0.05 ) 。结果：70 个组 A 病人(82.85%) 中的 58 个， 20/22 组 B (90.9%) 和 112/121 健康题目(92.56%) 是 seroconverted。seroconversion 率比在处理天真的 CHC 病人在控制组是显著地更高的(P = 0.04 ) 。相应的率在组 A 和组 B CHC 病人之间是可比较的(P = 0.38 ) 。绝大多数非应答者(10/14， 71.43%) 被 HCV 的 genotype-1 感染了。seroconversion 率在在瞬间 1 点的组 1 和 2 CHC 病人之间是可比较的(20% 对 26.7% ， P = 0.67 ) ，瞬间 2 (46.7% 对 60% ， P = 0.46 ) 并且瞬间 7 (86.7% 对 93.3% ， P = 0.54 ) 后续。结论：HBV 疫苗的 immunogenicity 似乎在与健康题目相比的 CHC 病人更低。SVR 后面的 IFN 正肋骨治疗不影响抗体反应到 HBV 疫苗。由 genotype-1 的感染似乎否定地影响 seroconversion 率。对 HBV 的种痘不以 anti-HBs seroconversion 率在加肋骨联合治疗的木钉期间是有益的。

Hepatitis B Vaccination in Medical and Dental Students: A Cross-Sectional Study

Background: Medical and dental students are at risk of Hepatitis B Virus (HBV) infection. The study aimed to assess the vaccination status against Hepatitis B Virus of students in clinical and non-clinical years of a private medical and dental college, and their knowledge, attitude, and awareness about the subject. Methods: A cross-sectional study was conducted using a pretested, self-administered questionnaire among 203 medical and dental students of CMH Lahore Medical College and Institute of Dentistry (CMH LMC & IOD) in Lahore, Pakistan. Participants were evaluated for their knowledge and vaccination status against Hepatitis B Virus. Students were considered to be fully vaccinated (recipients of 3 doses), partially vaccinated (recipients of 1 or 2 doses), and unvaccinated. Comparisons were made between students of clinical and non-clinical years. Data was entered and analysed using Statistical Package for the Social Sciences (SPSS) version 23. Results: Only 66% (n = 134) of the 203 participants had ever received a Hepatitis B Virus vaccine out of which a meagre 17.2% (n = 35) were fully vaccinated. No significant difference was found in vaccine uptake between students of clinical and non-clinical years (p-value = 0.181) despite significant differences seen in the knowledge of vaccination schedule (p-value = 0.001), the prevalence of needle-stick injuries (p-value = 0.001), and knowledge of protocols to be followed after a needle-stick injury (p-value = 0.001). Conclusion: Our study found that a large proportion of the student population is vulnerable to HBV infection. There is a need to create awareness regarding the subject to increase vaccine uptake. HBV vaccination should be offered to all currently enrolled students and be made mandatory at the time of admission in the future.

Optimal Control of Hepatitis B in a sub-Saharan African rural area

In this paper,we ameliorate the model proposed in[13],by incorporating the influence of hepatitis B e antigen(HBeAg)status of mothers on vertical transmission.We use the improved model to fit reported HBV new infections in the Zhejiang Province of China.Also to predict the course of the Hepatitis B(HBV)infection in this Chinese area,and in Tokombere,located in sub-Saharan Africa(SSA).Furthermore,we apply optimal control techniques in view to re-examine the effects of the newborn vaccination,the universal vaccination and the treatment of chronic carriers in preventing the HBV infection.Simulation results show that treatment slightly steps in the optimal strategy,while immunisation is an effective measure.On the other hand,they indicate that the control measures and immunization programs implemented in Zhejiang Province are effective.Besides,they suggest that in SSA,a package of several policies centred on birth dose vaccination should be implemented.

Factors Associated with Antibody Levels among Children Aged 15 to 59 Months Vaccinated against Hepatitis B during the Expanded Program on Immunization in Cameroon

Background: the hepatitis B virus infection remains a major public health problem worldwide. It can lead to a liver cirrhosis and/or hepatocellular carcinoma. The World Health Organisation (WHO) has recommended the implementation of generalised vaccination programs against hepatitis B. In Cameroon, this vaccine was introduced in the expanded program on immunization (EPI) in 2005, but few studies have assessed the immune response. Objective: the general objective of this study was to identify factors associated with antibody levels among children aged from 15 to 59 months vaccinated against hepatitis B during the EPI in Cameroon. Method: this was a cross-sectional study carried out from December 2021 to June 2022 in a paediatric centre of Yaoundé (Cameroon). We analysed the antibody level in children vaccinated against hepatitis B within the framework of the EPI. We enrolled children who had received a series of 3 intramuscular doses of hepatitis B vaccine at 6, 10 and 14 weeks after birth. Some children could receive a 4th booster dose between 12 months. The antibody level was assessed by measuring the anti-HBs in such children, aged 15 - 59 months. A good immunization was defined as a serum level of anti-HBs antibody level above 100 IU/mL;a poor immunization, for an anti-HBs antibody level between 10 and 100 IU/mL;and a non-immunization, for an anti-HBs antibody level < 10 IU/mL. Association between explored factors and poor or non-immunization was evaluated through the Chi square test. The significance threshold was defined at p < 0.05. Results: sixty subjects were included in the study with a slight female majority: 31 cases (52%). The average age was 38.5 ± 15.7 months (range 15 - 59 months). We found 32 (53%) cases of good immunization;21 (35%) of poor immunization;and 7 children (12%) with a non-immunization. The only factor associated with poor or non-immunization was the age between 37 - 59 months (p = 0.016). Conclusion: Anti HBs Antibody levels in children vaccinated against hepatitis B virus were globally satisfactory in our series. Results show an association between low antibody levels with older age (over 36 months), suggesting a circulating antibodies levels decrease over time, yet deemed protecting until 59 months.

Humoral and cellular immunogenecity of DNA vaccine based on hepatitis B core gene in rhesus monkeys

INTRODUCTIONHepatitis B virus (HBV) is the most commonetiologic agent for infectious liver diseases. It isestimated that there are more than 250 millionchronic HBV carriersin the world today and thereis a significant association among persistentinfection, liver cirrhosis and hepatocellularcarcinoma[1-3].

Long-term efectiveness of infancy low-dose hepatitis B vaccine immunization in Zhuang minority area in China

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Persistence of hepatitis B vaccine immune protection and response to hepatitis B booster immunization

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Long-term eficacy of plasma-derived hepatitis B vaccine among Chinese children:a 12-year folow-up study

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Recent advances in vaccination of non-responders to standard dose hepatitis B virus vaccine

Hepatitis B virus(HBV) infection is a global health problem. It is estimated there are more than 2 billion individuals exposed to the virus and 250 million are chronically infected. Hepatitis B is the cause of more than 600000 annual deaths due to cirrhosis and hepatocellular carcinoma. An effective vaccine exists and preventative initiatives center around universal vaccination especially in those at highest risk. Effective vaccination algorithms have led to a significant decline in the development of new infections and its devastating consequences. The vaccine is administered intramuscularly in three doses, with 95% showing long lasting serologic immunity. An additional fourth dose or a repeated higher dose three course regimen is given to those that fail to show immunity. Despite these additional regimens, some remain vulnerable to hepatitis B and are deemed nonresponders. Individuals with chronic disease states such as kidney disease, liver disease, diabetes mellitus, as well as those with a genetic predisposition, and those on immunomodulation therapy, have the highest likelihood of non-response. Various strategies have been developed to elicit an immune response in these individuals. These include increased vaccination dose, intradermal administration, alternative adjuvants, alternative routes of administration, co-administration with other vaccines, and other novel therapies. These alternative strategies can show improved response and lasting immunity. In summary, HBV vaccination is a major advance of modern medicine and all individuals at risk should be sought and vaccinated with subsequent adequate titers demonstrated.

New therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection:Increase of entecavir dosage

Chronic hepatitis B virus(HBV)infection(CHB)is a public health concern worldwide.Current therapies utilizing nucleos(t)ide analogs(NA)have not resulted in a complete cure for CHB.Furthermore,patients on long-term NA treatment often develop low-level viremia(LLV).Persistent LLV,in addition to causing the progression of liver disease or hepatocellular carcinoma,may shed light on the current plight of NA therapy.Here,we review the literature on LLV,NA treatment,and various doses of entecavir to find a strategy for improving the efficacy of this antiviral agent.For LLV patients,three therapeutic options are available,switching to another antiviral monotherapy,interferon-αswitching therapy,and continuing monotherapy.In real-world clinical practice,entecavir overdose has been used in antiviral therapy for CHB patients with NA refractory and persistent LLV,which encouraged us to conduct further in-depth literature survey on dosage and duration related entecavir studies.The studies of pharmacodynamics and pharmacokinetics show that entecavir has the maximal selected index for safety,and has great potential in inhibiting HBV replication,in all of the NAs.In the particular section of the drug approval package published by the United States Food and Drug Administration,entecavir doses 2.5-20 mg/d do not increase adverse events,and entecavir doses higher than 1.0 mg/d might improve the antiviral efficacy.The literature survey led us to two suggestions:(1)Increasing entecavir dose to 1.0 mg/d for the treatment of NA naïve patients with HBV DNA>2×106 IU/mL is feasible and would provide better prognosis;and(2)Further research is needed to assess the long-term toxic effects of higher entecavir doses(2.5 and 5.0 mg/d),which may prove beneficial in treating patients with prior NA treatment,partial virological response,or LLV state.

HBsAg, HBcAg, and combined HBsAg/HBcAg-based therapeutic vaccines in treating chronic hepatitis B virus infection

BACKGROUND: As the host immunity is diminished in patients with chronic hepatitis B (CHB), different approaches have been used to up-regulate their immune responses to produce therapeutic effects. But, cytokines, growth factors and polyclonal immune modulators could not exhibit sufficient therapeutic effects in these patients. Immune therapy with HBV-related antigens (vaccine therapy) has been used in CHB patients. But there is a paucity of information about the design of HBV antigen-based immune therapy in these patients. DATA SOURCE: Preclinical and clinical studies on immune therapy with HBsAg-based vaccine, HBcAg and combination of HBsAg/HBcAg-based vaccines have been discussed. RESULTS: HBsAg-based prophylactic vaccine was used as an immune therapeutic agent in CHB patients; however, monotherapy with HBsAg-based immune therapy could not lead to sustained control of HBV replication and/or liver damages. HBsAg-based vaccine was used as a combination therapy with cytokines, growth factors, and antiviral drugs. HBsAg-based vaccine was also used for cell-based therapy. However, satisfactory therapeutic effects of HBsAg-based vaccine could not be documented in CHB patients. In the mean time, evidences have supported that HBcAg-specific immunity is endowed with antiviral and liver protecting capacities in CHB patients. Recent data concentrate on the clinical use of combined HBsAg- and HBcAg-based vaccines in CHB patients.CONCLUSION: Antigen-based immune therapy with HBV- related antigens may be an alternative method for the treatment of CHB patients but proper designs of antigens, types of adjuvants, dose of vaccinations, and routes of administration need further analyses for the development of an effective regimen of immune therapy against HBV.

Toward a new era of hepatitis B virus therapeutics:The pursuit of a functional cure

Hepatitis B virus(HBV)infection,although preventable by vaccination,remains a global health problem and a major cause of chronic liver disease.Although current treatment strategies suppress viral replication very efficiently,the optimal endpoint of hepatitis B surface antigen(HBsAg)clearance is rarely achieved.Moreover,the thorny problems of persistent chromatin-like covalently closed circular DNA and the presence of integrated HBV DNA in the host genome are ignored.Therefore,the scientific community has focused on developing innovative therapeutic approaches to achieve a functional cure of HBV,defined as undetectable HBV DNA and HBsAg loss over a limited treatment period.A deeper understanding of the HBV life cycle has led to the introduction of novel direct-acting antivirals that exert their function through multiple mechanisms,including inhibition of viral entry,transcriptional silencing,epigenetic manipulation,interference with capsid assembly,and disruption of HBsAg release.In parallel,another category of new drugs aims to restore dysregulated immune function in chronic hepatitis B accompanied by lethargic cellular and humoral responses.Stimulation of innate immunity by pattern-recognition receptor agonists leads to upregulation of antiviral cytokine expression and appears to contribute to HBV containment.Immune checkpoint inhibitors and adoptive transfer of genetically engineered T cells are breakthrough technologies currently being explored that may elicit potent HBV-specific T-cell responses.In addition,several clinical trials are attempting to clarify the role of therapeutic vaccination in this setting.Ultimately,it is increasingly recognized that elimination of HBV requires a treatment regimen based on a combination of multiple drugs.This review describes the rationale for progressive therapeutic interventions and discusses the latest findings in the field of HBV therapeutics.