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.

Analysis of Occurrence and Mixed Infection of Sugarcane Bacilliform Virus Disease in Hainan Sugarcane-growing Area

[Objectives]The paper was to explore the occurrence and mixed infection of sugarcane bacilliform virus disease in Hainan sugarcane-growing area.[Methods]A total of 348 sugarcane leaf samples were collected from 7 sugarcane-growing areas in Hainan Province.Molecular detection of sugarcane bacilliform virus(SCBV)was carried out by PCR using specific primers.[Results]SCBV was detected in 244 out of 348 sugarcane samples,with an average detection rate of 70.11%.The highest detection rate was 76.66%in the Danzhou sugarcane-growing area,while the lowest was 57.14%in the Baisha sugarcane-growing area.The SCBV-positive samples were subjected to testing for SCYLV,SCSMV,SrMV,and SCMV,respectively.The results indicated that 106 out of 244 positive samples exhibited a single infection with SCBV,while 138 samples exhibited mixed infections with SCBV and other sugarcane viruses.The proportion of mixed infections among the SCBV-positive samples was as high as 56.56%.Among the various types of mixed infections,two-virus and three-virus mixed infections were the most prevalent.[Conclusions]SCBV has emerged as a significant threat to the secure production of sugarcane in the Hainan sugarcane-growing region.It presents an explosive infection in the Hainan sugarcane-growing region and frequently combines with other sugarcane viruses to infect sugarcane.The findings of this study will provide a theoretical foundation for the prevention and control of sugarcane bacilliform virus disease.

Transcriptome analysis reveals different response of resistant and susceptible rice varieties to rice stripe virus infection

Rice stripe disease,caused by rice stripe virus (RSV) which is transmitted by small brown planthopper (SBPH,Laodelphax striatellus Fallen),resulted in serious losses to rice production during the last 2 decades.Research on the molecular differences between resistant and susceptible rice varieties and the interaction between rice and RSV remains inadequate.In this study,RNA-Seq was used to analyze the transcriptomic differences between the resistant and susceptible rice varieties at different times post RSV infection.Through Gene Ontology (GO) annotation,the differentially expressed genes (DEGs) related to transcription factors,peroxidases,and kinases of 2 varieties at 3 time points were identified.Comparing these 2 varieties,the DEGs associated with these 3 GOs were numerically less in the resistant variety than in the susceptible variety,but the expression showed a significant up-or down-regulation trend under the conditions of|log_2(Fold change)|>0&P_(adj)<0.05 by significance analysis.Then through Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation,DEGs involved in some pathways that have a contribution to disease resistance including plant hormone signal transduction and plant–pathogen interaction were found.The results showed that resistance responses regulated by abscisic acid (ABA) and brassinosteroids (BR) were the same for 2 varieties,but that mediated by salicylic acid (SA) and jasmonic acid (JA)/ethylene (ET) were different.The DEGs in resistant and susceptible varieties at the 3 time points were identified in both PAMP-triggered immunity (PTI) and Effector proteintriggered immunity (ETI),with that most of the unigenes of the susceptible variety were involved in PTI,whereas most of the unigenes of the resistant variety were involved in ETI.These results revealed the different responses of resistant and susceptible varieties in the transcription level to RSV infection.

Hepatitis B virus infection in patients with Wilson disease:A large retrospective study

BACKGROUND Wilson disease(WD)is the most common genetic metabolic liver disease.Some studies have shown that comorbidities may have important effects on WD.Data on hepatitis B virus(HBV)infection in patients with WD are limited.AIM To investigate the prevalence and clinical impact of HBV infection in patients with WD.METHODS The clinical data of patients with WD were analyzed retrospectively,and the data of patients with concurrent WD and HBV infection were compared with those of patients with isolated WD.RESULTS Among a total of 915 WD patients recruited,the total prevalence of current and previous HBV infection was 2.1%[95%confidence interval(CI):1.2%-3.0%]and 9.2%(95%CI:7.3%-11.1%),respectively.The main finding of this study was the identification of 19 patients with concurrent WD and chronic hepatitis B(CHB)infection.The diagnosis of WD was missed in all but two patients with CHB infection.The mean delay in the diagnosis of WD in patients with concurrent WD and CHB infection was 32.5 mo,which was significantly longer than that in patients with isolated WD(10.5 mo).The rates of severe liver disease and mortality in patients with concurrent WD and CHB infection were significantly higher than those in patients with isolated WD(63.1%vs 19.3%,P=0.000 and 36.8%vs 4.1%,P<0.001,respectively).Binary logistic regression analysis revealed a significantly higher risk of severe liver disease at the diagnosis of WD in patients with current HBV infection[odds ratio(OR)=7.748;95%CI:2.890-20.774;P=0.000)]or previous HBV infection(OR=5.525;95%CI:3.159-8.739;P=0.000)than in patients with isolated WD.CONCLUSION The total prevalence of current HBV infection in patients with WD was 2.1%.The diagnosis of WD in CHB patients is usually missed.HBV infection is an independent risk factor for severe liver disease in WD patients.The diagnosis of WD should be ruled out in some patients with CHB infection.

Emerging perspectives on RNA virus-mediated infections:from pathogenesis to therapeutic interventions

RNA viruses continue to pose significant threats to global public health,necessitating a profound understanding of their pathogenic mechanisms and the development of effective therapeutic interventions.This manuscript provides a comprehensive overview of emerging perspectives on RNA virus-mediated infections,spanning from the intricate intricacies of viral pathogenesis to the forefront of innovative therapeutic strategies.A critical exploration of antiviral drugs sets the stage,highlighting the diverse classes of compounds that target various stages of the viral life cycle,underscoring the ongoing efforts to combat viral infections.Central to this discussion is the exploration of RNA-based therapeutics,with a spotlight on messenger RNA(mRNA)-based approaches that have revolutionized the landscape of antiviral interventions.Furthermore,the manuscript delves into the intricate world of delivery systems,exploring innovative technologies designed to enhance the efficiency and safety of mRNA vaccines.By analyzing the challenges and advancements in delivery mechanisms,this review offers a roadmap for future research and development in this critical area.Beyond conventional infectious diseases,the document explores the expanding applications of mRNA vaccines,including their promising roles in cancer immunotherapy and personalized medicine approaches.This manuscript serves as a valuable resource for researchers,clinicians,and policymakers alike,offering a nuanced perspective on RNA virus pathogenesis and the cutting-edge therapeutic interventions.By synthesizing the latest advancements and challenges,this review contributes significantly to the ongoing discourse in the field,driving the development of novel strategies to combat RNA virus-mediated infections effectively.

Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.

Characterization of the infectivity of an Indonesian Zika virus strain in mammalian cell lines

Objective:To characterize the infection patterns and growth characteristics of the Zika virus(ZIKV)strain JMB-185 from Indonesia in various mammalian cell lines.Methods:ZIKV was grown in human(A549,HEK293,HepG2,Huh7,Jurkat,and THP-1)and non-human mammalian(RAW264.7,Vero,and Vero76)cell lines.Viral replication kinetics were measured using plaque assay,while intra-and extracellular viral RNA concentrations were assessed using RT-PCR.Flow cytometry was used to quantify the infected cells and cell viability was measured using an MTT assay.The ability of ZIKV to infect cell lines was visualized using a fluorescence immunostaining assay.Results:This ZIKV strain preferentially infected the lung,kidney,and liver cell lines A549,HEK293,Huh7,Vero,and Vero76,but not the immune cells Jurkat,RAW264.7,and THP-1.By contrast,the ZIKV showed no sign of infection in HepG2 cells,while maintaining viral titer over 3 days post-infection,with no infection recorded in immunostaining,no increase in viral RNA,and no indication of cell deterioration.Conclusions:The Indonesian ZIKV strain has a similar infection profile as other strains,except for its poor infectivity on HepG2 cells.Information on the growth characteristics of Indonesia ZIKV will help expand our understanding of the biology of ZIKV which will be useful for various applications including antiviral discovery.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Prevention and Control Strategies of Nosocomial Infection and Effectiveness Evaluation in a Tertiary Teaching Hospital during the Epidemic of COVID-19

Objective: To evaluate the role of prevention and control strategies for nosocomial infection in a tertiary teaching hospital during the sudden outbreak of Corona Virus Disease 2019 (COVID-19). Methods: The hospital initiated an emergency plan involving multi-departmental defense and control. It adopted a series of nosocomial infection prevention and control measures, including strengthening pre-examination and triage, optimizing the consultation process, improving the hospital’s architectural composition, implementing graded risk management, enhancing personal protection, and implementing staff training and supervision. Descriptive research was used to evaluate the short-term effects of these in-hospital prevention and control strategies. The analysis compared changes in related evaluation indicators between January 24, 2020 and February 12, 2020 (Chinese Lunar New Year’s Eve 2020 to lunar January 19) and the corresponding lunar period of the previous year. Results: Compared to the same period last year, the outpatient fever rate increased by 1.85-fold (P P Conclusion: The nosocomial infection prevention and control strategies implemented during this specific period improved the detection and control abilities for the COVID-19 source of infection and enhanced the compliance with measures. This likely contributed significantly to avoiding the occurrence of nosocomial infection.

Demyelinating neuropathy in patients with hepatitis B virus: A case report

BACKGROUND Hepatitis B rarely leads to demyelinating neuropathy,despite peripheral neuropathy being the first symptom of hepatitis B infection.CASE SUMMARY A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves.Serological testing showed that these symptoms were due to hepatitis B.After undergoing treatment involving intravenous immunoglobulin and an antiviral agent,there was a notable improvement in his symptoms.CONCLUSION Although hepatitis B virus(HBV)infection is known to affect hepatocytes,it is crucial to recognize the range of additional manifestations linked to this infection.The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented;hence,prompt diagnostic and treatment are essential.The patient's positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.

Management strategies for common viral infections in pediatric renal transplant recipients

Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.

Hepatitis B virus reactivation in patients treated with monoclonal antibodies

Hepatitis B virus(HBV)reactivation poses a significant clinical challenge,espe-cially in patients undergoing immunosuppressive therapies,including mono-clonal antibody treatments.This manuscript briefly explores the complex rela-tionship between monoclonal antibody therapy and HBV reactivation,drawing upon current literature and clinical case studies.It delves into the mechanisms underlying this phenomenon,highlighting the importance of risk assessment,monitoring,and prophylactic measures for patients at risk.The manuscript aims to enhance the understanding of HBV reactivation in the context of monoclonal antibody therapy,ultimately facilitating informed clinical decision-making and improved patient care.This paper will also briefly review the definition of HBV activation,assess the risks of reactivation,especially in patients treated with monoclonal antibodies,and consider management for patients with regard to screening,prophylaxis,and treatment.A better understanding of patients at risk can help clinicians provide optimum management to ensure successful patient outcomes and prevent morbidity.

Streptococcus pneumoniae and Herpes Simplex Virus-1 Central Nervous System Co-Infection

Co-infections of the central nervous system (CNS) caused by bacterial and viral pathogens are considered to be rare. Herpes simplex virus type-1 (HSV-1) reactivation following Streptococcus pneumoniae infection is well described but most cases are related to oral or cutaneous lesions or in respiratory samples. HSV-1 CNS reactivation after Streptococcus pneumoniae meningitis is a very rare event and may have significant morbidity and mortality. In this case report, we describe a 71-year-old female patient that presented with a history of abdominal pain and confusion/disorientation that had tonic-clonic seizures while in the Emergency Department. The diagnostic work-up confirmed CNS co-infection caused by Streptococcus pneumoniae and HSV-1. Of note, beyond age, the patient had no known risk factors for both entities and recovered fully after antibiotic and antiviral therapy. This case underlines that clinicians must be aware of CNS co-infection despite being a rare diagnosis. This should be suspected particularly in patients who present an unusual clinical course of CNS infection.

Chronic hepatitis B and occult infection in chemotherapy patients-evaluation in oncology and hemato-oncology settings:The CHOICE study

BACKGROUND Reactivation of hepatitis B virus(HBV)infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies,including cancer chemotherapy.HBV reactivation can cause significant morbidity and even mortality,which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis.AIM To determine the prevalence of chronic HBV(CHB)and occult HBV infection(OBI)among oncology and hematology-oncology patients undergoing chemo-therapy.METHODS In this observational study,the prevalence of CHB and OBI was assessed among patients receiving chemotherapy.Serological markers of HBV infection[hepatitis B surface antigen(HBsAg)/anti-hepatitis B core antigen(HBc)]were evaluated for all patients.HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc.RESULTS The prevalence of CHB in the study cohort was determined to be 2.3%[95%confidence interval(95%CI):1.0-4.2].Additionally,the prevalence of OBI among the study participants was found to be 0.8%(95%CI:0.2-2.3).CONCLUSION The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy.Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection,which can lead to increased morbidity and mortality.

Global epidemiology of hepatitis C virus infection: an up-date of the distribution and circulation of hepatitis C virus genotypes

AIM To review Hepatitis C virus(HCV) prevalence and genotypes distribution worldwide.METHODS We conducted a systematic study which represents one of the most comprehensive effort to quantify global HCV epidemiology,using the best available published data between 2000 and 2015 from 138 countries(about 90% of the global population),grouped in 20 geographical areas(with the exclusion of Oceania),as defined by the Global Burden of Diseases project(GBD). Countries for which we were unable to obtain HCV genotype prevalence data were excluded from calculations of regional proportions,although their populations were included in the total population size of each region when generating regional genotype prevalence estimates.RESULTS Total global HCV prevalence is estimated at 2.5%(177.5 million of HCV infected adults),ranging from 2.9% in Africa and 1.3% in Americas,with a global viraemic rate of 67%(118.9 million of HCV RNA positive cases),varying from 64.4% in Asia to 74.8% in Australasia. HCV genotype 1 is the most prevalent worldwide(49.1%),followed by genotype 3(17.9%),4(16.8%) and 2(11.0%). Genotypes 5 and 6 are responsible for the remaining < 5%. While genotypes 1 and 3 are common worldwide,the largest proportion of genotypes 4 and 5 is in lower-income countries. Although HCV genotypes 1 and 3 infections are the most prevalent globally(67.0% if considered together),other genotypes are found more commonly in lowerincome countries where still account for a significant proportion of HCV cases.CONCLUSION A more precise knowledge of HCV genotype distribution will be helpful to best inform national healthcare models to improve access to new treatments.

Follow-up study of hepatitis C virus infection in uremic patients on maintenance hemodialysis for 30 months

INTRODUCTIONA high prevalence of antibodies to hepatitis C virus(HCV)(range from 3.3%-80%)has beenreported in hemodialysis(HD)patients,andworrisome as it often becomes chronic and induceschronic liver disease,therefore thenephrologists face a major challenge of how toprevent it.The main route of HCV transmission

Hepatitis B virus infection and genotype in asymptomatic people from 10 ethnic groups in Yunnan, China

AIM: To evaluate the infection and genotype distribution of hepatitis B virus(HBV) in ethnic groups in Yunnan, China.METHODS: Two thousand five hundred and eightyfour asymptomatic local people from 10 ethnic groups were investigated in Yunnan, China. Infection and genotype distribution were evaluated by serological and genetic methods. Genotyping was verified by sequencing. Ethnic genotype distribution was compared by proportion test. RESULTS: Four types of infection model based on HBV serum markers were identified, and the average HBV infection rate was 5.7% in those asymptomatic local people. The genotype prevalence was 59.6% for B, 21.1% for C and 19.3% BC; subgenotypes Ba, Cs and Ce were identified in this study. Hepatitis B surface antigen-positive rate and the proportion of genotype B were significantly lower in ethnic groups with a northern origin compared to those with a southern origin(50% vs 73.9%, P = 0.037; 4.2% vs 10.5%, P = 0.000).CONCLUSION: Genotype B is dominant and genotype BC has high occurrence in asymptomatic local ethnic groups in Yunnan. HBV infection status and genotype distribution may associate with ethnic origin.

Current therapeutic strategies for recurrent hepatitis B virus infection after liver transplantation

Hepatitis B virus (HBV)-related liver disease is the leading indication for liver transplantation (LT) in Asia,especially in China.With the introduction of hepatitis B immunoglobulin (HBIG) and oral antiviral drugs,the recurrent HBV infection rate after LT has been evidently reduced.However,complete eradication of recurrent HBV infection after LT is almost impossible.Recurrent graft infection may lead to rapid disease progression and is a frequent cause of death within the fi rst year after LT.At present,the availability of new oral medications,especially nucleoside or nucleotide analogues such as adefovir dipivoxil,entecavir and tenofovir disoproxil fumarate,further strengthens our ability to treat recurrent HBV infection after LT.Moreover,since combined treatment with HBIG and antiviral agents after liver re-transplantation may play an important role in improving the prognosis of recurrent HBV infection,irreversible graft dysfunction secondary to recurrent HBV infection in spite of oral medications should no longer be considered an absolute contraindication for liver re-transplantation.Published reviews focusing on the therapeutic strategies for recurrent HBV infection after LT are very limited.In this article,the current therapeutic strategies for recurrent HBV infection after LT and evolving new trends are reviewed to guide clinical doctors to choose an optimal treatment plan in different clinical settings.

The prevalence of transfusion transmitted virus infection in blood donors

INIRODUCIIONA newly discovered DNA virus,transfusiontransmitted virus (TTV),was reported as a cause ofpost-transfusion hepatitis of unknown etiology inJapan.In order to investigate TTV prevalence insouthern China,a study was carried out amongblood donors,patients with liver diseases andhemodialysis to determine the epidemiologicalcharateristics.

Innate immune targets of hepatitis B virus infection

Approximately 400 million people are chronically infected with hepatitis B virus(HBV) globally despitethe widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection.