Hepatitis B core-related antigen as a promising serological marker for monitoring hepatitis B virus cure

Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and covalently closed circular DNA(cccDNA)clearance.Serum hepatitis B core-related antigen(HBcrAg)is an emerging HBV marker comprising three components:HBeAg,hepatitis B core antigen,and p22cr.It responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serolo-gical testing.There is a strong correlation,and a decrease in its level corresponds to sustained viral suppression.In patients with chronic hepatitis B(CHB),serum HBcrAg levels are good predictors of HBeAg seroconversion(both spontaneous and after antiviral therapy),particularly in HBeAg-positive patients.Both low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion,which may serve as a good surrogate option for treatment endpoints.In this review,we summarize the role of serum HBcrAg in the treat-ment of CHB.Therefore,long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen,making it a promising marker for monitoring HBV cure.

Timing of post-vaccination tests in infants born to mothers with chronic hepatitis B virus infection

Immunoprophylaxis is routinely recommended for infants born to mothers with hepatitis B virus(HBV)infection within the first 12-24 hours.Detection of he-patitis B surface antibody(HBsAb)resulting from hepatitis B immunoglobulin administered at birth may be perceived as a real vaccine response.This makes it difficult to detect HBV infection.For this reason,it is recommended that infants born to hepatitis B surface antigen positive mothers and who received immunop-rophylaxis at birth should have HBsAb testing when they are 9-15 months old.

Hepatitis B surface antigen-negative but hepatitis B envelope antigen-positive false occult hepatitis B virus infection:A case report

BACKGROUND Occult hepatitis B infection(OBI)is characterized by the detection of hepatitis B virus(HBV)DNA in serum(usually HBV DNA<200 IU/mL)or the liver but negativity for hepatitis B surface antigen(HBsAg).The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg.HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection.CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level.The patient was initially diagnosed as having OBI.However,sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein,which affects the formation of a disulfide bond that is associated with the formation of a loop.It is well known that there is an overlap between the S protein and Pol protein.We found that this new insertion site occurred in polymerase/reverse transcriptase domain,indi-cating that this insertion might be involved in HBV pathogenicity.The patient was finally diagnosed with a false OBI.CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels.

Prevalence of cardiometabolic co-morbidities in patients with vs persons without chronic hepatitis B: The FitLiver cohort study

BACKGROUND Chronic hepatitis B(CHB)affects>300 million people worldwide.The combi-nation of CHB and cardiometabolic co-morbidities increases the risk of liver-related morbidity and mortality.However,international guidelines for CHB treatment do not provide recommendations for follow-up examinations or treatment of patients with CHB and cardiometabolic comorbidities.In studies investigating cardiometabolic co-morbidity in patients with CHB,inconsistent findings have been observed,and both lower and higher prevalence of car-diometabolic co-morbidities compared to the general population have been re-ported.It is unclear whether patients with CHB living in Denmark have an increased prevalence of cardiometabolic co-morbidities.We examined patients with CHB and age-,sex-,body mass index(BMI)-,and country-of-birth matched comparison group.Defining cardiometabolic co-morbidity:Obesity(BMI>25 kg/m2/abnormal waist-to-hip ratio),metabolic dysfunction-associated steatotic liver disease(MASLD),hypercholesterolemia(total-cholesterol>5 mmol/L/statin use),hypertension(systolic≥135 mmHg/diastolic≥85 mmHg/antihypertensive medication)and type 2 diabetes(T2D)(2-hour oral glucose tolerance test glucose>11.1 mmol/L/HbA1c>48 mmol/mol/antidiabetic medication).Physical activity was evaluated using maximal oxygen consumption(VO2max),activity monitors,and a questionnaire.RESULTS We included 98 patients with CHB and 49 persons in the comparison group.The two groups were well-matched,showing no significant differences in age,sex,BMI,country-of-birth,education,or employment.Among patients with CHB,the following prevalence of cardiometabolic co-morbidity was found:77%were obese,45%had MASLD,38%had hypercholesterolemia,26%had hypertension,and 7%had T2D,which did not differ significantly from the comparison group,apart from lower prevalence of hemoglobin A1c(HbA1c)≥48 mmol/L or known T2D.Both groups had low VO2max of 27 mL/kg/minute in the patients with CHB and 30 mL/kg/minute in the comparison group,and the patients with CHB had a shorter self-assessed sitting time.CONCLUSION The patients with CHB and the comparison group were well-matched and had a similar prevalence of car-diometabolic comorbidities.Furthermore,both groups had low levels of physical fitness.

Hepatitis B virus infection and its treatment in Eastern Ethiopia

Hepatitis B virus(HBV)infection causes acute and chronic hepatitis,compensated and decompensated cirrhosis,and hepatocellular carcinoma worldwide.The actual status of HBV infection and its treatment in certain regions of Asian and African countries,including Ethiopia,has not been well-documented thus far.Antiviral therapy for HBV infection can prevent the progression of HBV-related liver diseases and decrease the HBV-related symptoms,such as abdominal symp-toms,fatigue,systemic symptoms and others.In Eastern Ethiopia,HBV-infected patients with cirrhosis were found to be positive for the HBV e antigen and to have a higher viral load than those without cirrhosis.Notably,54.4%of patients practiced khat chewing and 18.1%consumed excessive amounts of alcohol.Teno-fovir disoproxil fumarate effectively suppressed HBV DNA in those infected with HBV.It is important to elucidate the actual status of HBV infection in Eastern Ethiopia to eliminate HBV infection worldwide by 2030.HBV vaccination and the educational programs for Health Science students that provide practical strategies could help to reduce HBV infection in Eastern Ethiopia.

Evaluating the scope of human leukocyte antigen polymorphisms influencing hepatitis B virus-related liver cancer and cirrhosis through multi-clustering analysis

Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering analysis.Here,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.

Clinical features of abnormalα-fetoprotein in 15 patients with chronic viral hepatitis B after treatment with antiviral drugs

BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients following long-term antiviral treatment.However,in the absence of imaging evidence of liver cancer,a reasonable expla-nation for this phenomenon is still lacking.AIM To explore the causes of abnormal AFP in patients with CHB who were not diag-nosed with liver cancer.METHODS From November 2019 to May 2023,15 patients with CHB after antiviral treatment and elevated AFP were selected.Clinical data and quality indicators related to laboratory testing,imaging data,and pathological data were obtained through inpatient medical records.RESULTS All patients had increased AFP and significantly elevated IgG.Cancer was excluded by imaging examination.Only four patients had elevated alanine ami-notransferase,10 had elevated aspartate aminotransferase,nine had elevated total bilirubin,and two had antinuclear antibodies.The liver biopsy and histopatho-logical examination indicated that 14 patients had rosette,moderate,or higher interfacial inflammation,lymphocyte infiltration,and severe hepatic fibers(11 cases),which was consistent with the pathological features of autoimmune hepa-titis(AIH).After 8-12 week of hormone therapy,the levels of AFP and IgG,and liver function returned to normal(P<0.05).CONCLUSION For patients with CHB and elevated AFP after antiviral treatment,autoimmune hepatitis should be considered.CHB with AIH is clinically insidious and difficult to detect,and prone to progression to cirrhosis.Liver puncture pathological examination should be performed when necessary to confirm diagnosis.

Hepatitis B virus infection and metabolic dysfunction associated steatotic liver disease:Rising pandemic with complex interaction

Due to sedentary lifestyle and rising prevalence of obesity,patients with general population and those who are infected with chronic hepatitis B are found to have metabolic dysfunction associated steatotic liver disease(MASLD).Both chronic hepatitis B virus(HBV)infection and MASLD can damage hepatocytes in their own way,but concomitant HBV-MASLD has its own clinical implications.Cherry on top is the presence of diabetes mellitus,hypertension or obesity which added more chances of unfavorable outcomes in these patients.In this article,we co-mment on the article by Wang et al published in the recent issue.This article provides a comprehensive overview of the complex interaction between HBV-MASLD,HBV alone and MASLD alone patients.We discuss key findings from recent studies,including the promising outcomes observed in patients with concurrent HBV and MASLD,warrants further research.The insights presented here offer renewed understanding of this complex interaction.

Reactivation of hepatitis B virus infection – an important aspect of multifaceted problem

In this editorial we comment on the article published in the recent issue of the W orld Journal of Gastroenterology.We focus specifically on the problem of occult hepatitis B virus(HBV)infection,that is a result of previous hepatitis B(PHB)and a source for reactivation of HBV.The prevalence of PHB is underestimated due to the lack of population testing programs.However,this condition not only com-plicate anticancer treatment,but may be responsible for the development of other diseases,like cancer or autoimmune disorders.Here we unveil possible mecha-nisms responsible for realization of these processes and suggest practical approa-ches for diagnosis and treatment.

Recurrence and influencing factors of hepatitis B surface antigen seroclearance induced by peginterferon alpha-based regimens

BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations of this strategy unclear.AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-αregimens.METHODS This prospective,multicenter,observational study was conducted from November 2015 to June 2021 at three Chinese hospitals:The Second Affiliated Hospital of Xi’an Jiaotong University,Ankang Central Hospital,and The Affiliated Hospital of Yan’an University.Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus(HBV)markers,HBV DNA,and liver function.The primary outcome was HBV recurrence,defined as the reemergence of HBsAg,HBV DNA,or both,at least twice within 4-8 weeks of follow-up.RESULTS In total,121 patients who achieved HBsAg seroclearance were enrolled.After a median follow-up of 84.0(48.0,132.0)weeks,four subjects were lost to follow-up.HBsAg recurrence was detected in 16 patients.The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%.Multivariate logistic regression analysis demonstrated that consolidation time<12 weeks[odds ratio(OR)=28.044,95%CI:4.525-173.791]and hepatitis B surface antibody disappearance during follow-up(OR=46.445,95%CI:2.571-838.957)were strong predictors of HBsAg recurrence.HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed.CONCLUSION HBsAg seroclearance following peg-IFN-αtreatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.

Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

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.

Advances in treatment and prevention of hepatitis B

Chronic hepatitis B(CHB)continues to contribute to worldwide morbidity and mortality significantly.Scientists,clinicians,pharmaceutical companies,and health organizations have dedicated substantial Intellectual and monetary resources to finding a cure,increasing immunization rates,and reducing the global burden of CHB.National and international health-related organizations including the center for disease control,the national institute of health,the American Association for the study of liver disease(AASLD),The European association for the study of the Liver(EASL),The Asia Pacific association for the study of the Liver(APASL)and the world health organization release periodic recommendations for disease prevention and treatment.Our review of the most recent guidelines by EASL,AASLD,APASL,and Taiwan Association for the Study of the Liver revealed that an overwhelming majority of cited studies were published before 2018.We reviewed Hepatitis B-related literature published 2018 onwards to identify recent developments and current barriers that will likely direct future efforts towards eradicating hepatitis B.The breakthrough in our understanding of the hepatitis B virus life cycle and resulting drug development is encouraging with significant room for further progress.Data from high-risk populations,most vulnerable to the devastating effects of hepatitis B infection and reactivation remain sparse.Utilization of systems approach,optimization of experimental models,identification and validation of next-generation biomarkers,and precise modulation of the human immune response will be critical for future innovation.Within the foreseeable future,new treatments will likely complement conventional therapies rather than replace them.Most Importantly,pragmatic management of CHB related population health challenges must be prioritized to produce real-world results.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

Antiviral treatment standards for hepatitis B:An urgent need for expansion

The present letter to the editor is related to the review with the title“Past,present,and future of long-term treatment for hepatitis B virus.”Chronic hepatitis B(CHB)represents an important and pressing public health concern.Timely identification and effective antiviral therapy hold the potential to reduce liver-related mortality attributable to chronic infection with hepatitis B virus(HBV)substantially.However,the current global treatment rates for CHB remain conspicuously low,with the excessively stringent treatment criteria advocated by national CHB guidelines being a contributing factor to these low rates.Nevertheless,recent strides in comprehending this malady and the emergence of novel antiviral agents prompt the imperative re-evaluation of treatment standards to extend the sphere of potential beneficiaries.An impending need arises for a novel paradigm for the classification of patients with CHB,the expansion of antiviral treatment eligibility for HBV-infected individuals,and even the streamlining of the diagnostic process for CHB to amplify cost-effectiveness and augment survival prospects.

Risk of hepatitis B virus reactivation in cancer patients undergoing treatment with tyrosine kinase-inhibitors

This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et al.In this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive measures.The aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management strategies.TKIs are considered to be an intermediate(1%-10%)of HBVr.Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface antibody.Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV.Nucleoside or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during immunosuppression.Conversely,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains.However,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.

Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies:Who and Why?

The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.

Risk of hepatic decompensation from hepatitis B virus reactivation in hematological malignancy treatments

In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton’s tyrosine kinase(BTK)inhibitor therapy.First of all,we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response,focusing our attention on the protective role of anti-HBs.We then carefully analyzed literature data on the risk of HBV reactivation(HBVr)in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies.Based on literature data,we suggested that several factors may contribute to the different risks of HBVr:The type of hematologic malignancy;the type of therapy(BTK inhibitors,especially second-generation,seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors);previous exposure to an anti-CD20 as first-line therapy;and ethnicity and HBV genotype.Therefore,the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.

Elimination of hepatitis B as a public health threat:Addressing the challenge and taking action

Despite the significant efforts made in recent years,the latest data from the World Health Organization indicates that there are substantial challenges in achieving the elimination of hepatitis B virus(HBV)infection by 2030.The article in the World Journal of Hepatology by Ismael et al highlighted the limited accessibility to screening and antiviral treatment for HBV infection in eastern Ethiopia.Therefore,the editorial comments on this article will focus on the current challenges and recent efforts in the prevention and treatment of chronic hepatitis B,particularly emphasizing the expansion of screening and antiviral therapy,as well as feasible strategies to improve accessibility for HBV testing,antiviral therapy,and adherence enhancement.

Chronic hepatitis B:Prevent,diagnose,and treat before the point of no return

Hepatitis B remains a significant global health challenge,contributing to substantial morbidity and mortality.Approximately 254 million people world-wide live with Chronic hepatitis B(CHB),with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions.Alarmingly,only about 13.4%of the individuals infected with this disease have been diagnosed,and awareness of hepatitis B virus(HBV)infection status is as low as 1%in sub-Saharan Africa.In 2022,CHB led to 1.1 million deaths globally.The World Health Organization(WHO)has set a target of eliminating hepatitis B as a public health concern by 2030;however,this goal appears increasingly unattainable due to multiple challenges.These challenges include low vaccination coverage;a large number of undiagnosed cases;a low proportion of patients eligible for treatment under current guidelines;limited access to healthcare;and the costs associated with lifelong treatment.Treatment of HBV can yield significant clinical benefits within a long window of opportunity.However,the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage.This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.