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 ...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.展开更多
BACKGROUND Chronic viral B hepatitis(CHB)is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis.Currently,although combinations of different laboratory methods are used in the...BACKGROUND Chronic viral B hepatitis(CHB)is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis.Currently,although combinations of different laboratory methods are used in the follow-up and treatment of CHB,the failure of these procedures in some cases has led to the necessity of developing new approaches.In CHB,the intrahepatic expression pattern of viral antigens,including hepatitis B surface antigen(HBsAg),is related to different phases of inflammation.However,many studies have focused on the intracytoplasmic properties of HBsAg staining,and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods.AIM To investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB.METHODS A total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study.Following diagnosis,all patients were treated with entecavir(0.5 mg)and followed up at three-month intervals.The percentage of immunohistochemical HBsAg(p-HBsAg)expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis.The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications.RESULTS A positive correlation between p-HBsAg and serum levels of hepatitis B virus(HBV)DNA and HBsAg was observed(P<0.001).The p-HBsAg value was significantly higher in younger patients than in older patients.When the groups were categorized according to the hepatitis B e antigen(HBeAg)status in HBeAgpositive cases,p-HBsAg was correlated with HBV DNA,hepatitis activity index(HAI)and fibrosis scores(P<0.001).In this group,p-HBsAg and HBsAg expression patterns were also correlated with the viral response(VR)and the serological response(SR)(P<0.001).Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR(P<0.001).In HBeAg-negative patients,although HBsAg expression patterns were correlated with both HAI and fibrosis,no relationship was observed among p-HBsAg,clinicopathological factors and VR.CONCLUSION In pretreatment liver biopsies,the immunohistochemical determination of HBsAg expression by quantitative methods,beyond its distribution within the cell,may be a good predictor of the treatment response,especially in HBeAg-positive cases.展开更多
Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list f...Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28(2%) received the graft from hepatitis B surface antigen positive(HBs Ag)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary nonfunction, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3-and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBs Agpositive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.展开更多
BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)-positive carrier status and liver cancer has been extensively studied.However,the epigenetic changes that occur during progression from HBsAg-posi...BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)-positive carrier status and liver cancer has been extensively studied.However,the epigenetic changes that occur during progression from HBsAg-positive carrier status or cirrhosis to liver cancer are unknown.The epigenetic modification of DNA hydroxymethylation is critical in tumor development.Further,5-hydroxymethylcytosine(5hmC)is an important base for DNA demethylation and epigenetic regulation.It is also involved in the assembly of chromosomes and the regulation of gene expression.However,the mechanism of action of 5hmC in HBsAgpositive carriers or patients with cirrhosis who develop liver cancer has not been fully elucidated.AIM To investigate the possible epigenetic mechanism of HBsAg-positive carriers and hepatocellular carcinoma(HCC)progression from cirrhosis.METHODS Forty HBsAg-positive carriers,forty patients with liver cirrhosis,and forty patients with liver cancer admitted to the First People's Hospital of Yongkang between March 2020 and November 2021 were selected as participants.Free DNA was extracted using a cf-DNA kit.cfDNA was extracted by 5hmC DNA sequencing for principal component analysis,the expression profiles of the three groups of samples were detected,and the differentially expressed genes(DEGs)modified by hydroxymethylation were screened.Bioinformatic analysis was used to enrich DEGs,such as in biological pathways.RESULTS A total of 16455 hydroxymethylated genes were identified.Sequencing results showed that 32 genes had significant 5hmC modification differences between HBsAg carriers and liver cancer patients,of which 30 were upregulated and 2 downregulated in patients with HCC compared with HBsAg-positive carriers.Significant 5hmC modification differences between liver cirrhosis and liver cancer patients were identified in 20 genes,of which 17 were upregulated and 3 were downregulated in patients with HCC compared with those with cirrhosis.These genes may have potential loci that are undiscovered or unelucidated,which contribute to the development and progression of liver cancer.Analysis of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes showed that the major signaling pathways involved in the differential genes were biliary secretion and insulin secretion.The analysis of protein interactions showed that the important genes in the protein-protein interaction network were phosphoenolpyruvate carboxykinase and solute carrier family 2.CONCLUSION The occurrence and development of liver cancer involves multiple genes and pathways,which may be potential targets for preventing hepatitis B carriers from developing liver cancer.展开更多
Hepatitis B Virus (HBV) infections affect about 400 million people globally and cause about 1.4 million deaths annually. The virus displays high levels of genetic variations/mutations, some of which are immune escape ...Hepatitis B Virus (HBV) infections affect about 400 million people globally and cause about 1.4 million deaths annually. The virus displays high levels of genetic variations/mutations, some of which are immune escape mutants. The prevalence of HBV infection in Kenya is high at about 8%. This study aimed at identifying and characterizing HBV immune escape mutants in Kenya. From 547 HBV sequences available in Kenya in NCBI, and HBVdb databases in July 2021, 120 full sequences were retrieved. The S gene sequences at position 1-225, which included the “a” determinant region of the gene were analyzed using various bioinformatics tools such as Bioedit software, and Emboss Cons. The clinical significance was flagged from the search of peer-reviewed journals. Forty-six HBV-positive blood donor samples were obtained from the Kenya National Blood Transfusion Services without personal identifiers, DNA extracted, and sequenced targeting positions 1 to 520 of S genes. Mutations were similarly identified from seventeen sequences after cleaning and analysis. Out of 120 sequences that were extracted from databases and analyzed, 79 different mutations were identified. Fifteen of them were of clinical importance with an occurrence frequency of at least 5% were obtained. The majority (64.6%, n = 51), with S207N and A194V being most dominant, could result in immune escape and reduced HBsAg detection signals while 24.1% (n = 19) could result in immune escape/reduced HBsAg detection signals and high probability of hepatocellular carcinoma. Most likely to occur on the amino acids Alanine, Lysine, Serine, Asparagine, and Valine in decreasing order. The most dominant genotype was found to be Genotype A (N = 10), while four sequences were Genotype D. In contrast to the in-silico studies, the sequences from HBV samples from blood donors did not demonstrate the presence of S207N and A194V mutations and all the genotypes were type A1. Only two (13.3%) samples showed the same mutations of sK122R and sT143S for both in-silico analysis and actual sequenced samples. This study did not identify G145R mutation which is the commonest mutation within the HBsAg immunodominant “a” determinant that is associated with immune escape. The concordance of mutations in “a” determinant region of HBsAg gene among various studies is minimal. The study identified new mutations (sA194Y, sS207, sA194S, sS207I, sP46A, sA194T, sS207I, sP46R, and sT143P) that had not been published before. Four (20%) of the mutations were clinically significant. These included sS207R, sT143S, sC76F and sK122R.展开更多
BACKGROUND Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues(NAs)rarely achieve hepatitis B surface antigen(HBsAg)loss.AIM To evaluate if the addition of pegylated interferon(Pe...BACKGROUND Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues(NAs)rarely achieve hepatitis B surface antigen(HBsAg)loss.AIM To evaluate if the addition of pegylated interferon(Peg-IFN)could decrease HBsAg and hepatitis B core-related antigen(HBcrAg)levels and increase HBsAg loss rate in patients under NAs therapy.METHODS Prospective,non-randomized,open-label trial evaluating the combination of Peg-IFN 180μg/week plus NAs during forty-eight weeks vs NAs in monotherapy.Hepatitis B e antigen-negative non-cirrhotic chronic hepatitis B patients of a tertiary hospital,under NAs therapy for at least 2 years and with undetectable viral load,were eligible.Patients with hepatitis C virus,hepatitis D virus or human immunodeficiency virus co-infection and liver transplanted patients were excluded.HBsAg and HBcrAg levels(log10 U/mL)were measured at baseline and during ninety-six weeks.HBsAg loss rate was evaluated in both groups.Adverse events were recorded in both groups.The kinetic of HBsAg for each treatment group was evaluated from baseline to weeks 24 and 48 by the slope of the HBsAg decline(log10 IU/mL/week)using a linear regression model.RESULTS Sixty-five patients were enrolled,61%receiving tenofovir and 33%entecavir.Thirty-six(55%)were included in Peg-IFN-NA group and 29(44%)in NA group.After matching by age and treatment duration,baseline HBsAg levels were comparable between groups(3.1 vs 3.2)(P=0.25).HBsAg levels at weeks 24,48 and 96 declined in Peg-IFN-NA group(-0.26,-0.40 and-0.44)and remained stable in NA group(-0.10,-0.10 and-0.10)(P<0.05).The slope of HBsAg decline in Peg-IFN-NA group(-0.02)was higher than in NA group(-0.00)(P=0.015).HBcrAg levels did not change.Eight(22%)patients discontinued Peg-IFN due to adverse events.The HBsAg loss was achieved in 3(8.3%)patients of the Peg-IFN-NA group and 0(0%)of the NA group.CONCLUSION The addition of Peg-IFN to NAs caused a greater and faster decrease of HBsAg levels compared to NA therapy.Side effects of Peg-IFN can limit its use in clinical practice.展开更多
BACKGROUND Hepatitis B surface antigen(HBsAg)loss,a functional cure in patients with chronic hepatitis B(CHB)undergoing antiviral therapy,might be an ideal endpoint of antiviral treatment in clinical practice.The fact...BACKGROUND Hepatitis B surface antigen(HBsAg)loss,a functional cure in patients with chronic hepatitis B(CHB)undergoing antiviral therapy,might be an ideal endpoint of antiviral treatment in clinical practice.The factors that contribute to the functional cure remain unclear,and the predictors of functional cure are worth exploring.The concentration and kinetics of soluble programmed death-1(sPD-1)in patients with CHB may play an important role in elucidating the immune response associated with functional cure after nucleos(t)ide analogs therapy.AIM To investigate the factors associated with HBsAg loss and explore the influence of sPD-1 Levels.METHODS This study analyzed the data and samples from patients with CHB who underwent antiviral treatment in a non-interventional observational study conducted at Peking University First Hospital in Beijing(between 2007 and 2019).All patients were followed up:Serum samples were collected every 3 mo during the first year of antiviral treatment and every 6 mo thereafter.Patients with positive hepatitis B e antigen levels at baseline and with available sequential samples who achieved HBsAg loss during antiviral treatment served as the case group.This case group(n=11)was further matched to 44 positive hepatitis B e anti patients without HBsAg loss as controls.The Spearman’s rank correlation test and receiver operating characteristic curves analysis were performed.RESULTS The sPD-1 Levels were higher in patients with HBsAg loss than in those without HBsAg loss from baseline to month 96,and the differences were significant between the groups at baseline(P=0.0136),months 6(P=0.0003),12(P<0.0001),24(P=0.0007),48(P<0.0001),and 96(P=0.0142).After 6 mo of antiviral treatment,the sPD-1 levels were positively correlated with alanine transaminase(ALT)levels(r=0.5103,P=0.0017),and the sPD-1 levels showed apparent correlation with ALT(r=0.6883,P=0.0192)and HBV DNA(r=0.5601,P=0.0703)levels in patients with HBsAg loss.After 12 mo of antiviral treatment,the sPD-1 levels also showed apparent correlation with ALT(r=0.8134,P=0.0042)and HBV DNA(r=0.6832,P=0.0205)levels in patients with HBsAg loss.The sPD-1 levels were negatively correlated with HBsAg levels in all patients after 12 mo of antiviral treatment,especially at 24(r=-0.356,P=0.0497)and 48(r=-0.4783,P=0.0037)mo.After 6 mo of antiviral treatment,the AUC of sPD-1 for HBsAg loss was 0.898(P=0.000),whereas that of HBsAg was 0.617(P=0.419).The cut-off value of sPD-1 was set at 2.34 log pg/mL;the sensitivity and specificity were 100%and 66.7%,respectively.CONCLUSION The sPD-1 levels at 6 mo can predict HBsAg loss after 144 mo of antiviral treatment.展开更多
AIM To investigate the functional role and underlying molecular mechanism of mi R-29 a in hepatitis B virus(HBV) expression and replication.METHODS The levels of mi R-29 a and SMARCE1 in HBV-infected Hep G2.2.15 cells...AIM To investigate the functional role and underlying molecular mechanism of mi R-29 a in hepatitis B virus(HBV) expression and replication.METHODS The levels of mi R-29 a and SMARCE1 in HBV-infected Hep G2.2.15 cells were measured by quantitative real-time PCR and western blot analysis. HBV DNA replication was measured by quantitative PCR and Southern blot analysis. The relative levels of hepatitis B surface antigen and hepatitis B e antigen were detected by enzyme-linked immunosorbent assay. The Cell Counting Kit-8(CCK-8) was used to detect the viability of Hep G2.2.15 cells. The relationship between mi R-29 a and SMARCE1 were identified by target prediction and luciferase reporter analysis.RESULTS mi R-29 a promoted HBV replication and expression, w h i le S MA R C E 1 r e p r e s s e d H B V r e p lic a t io n a n d expression. Cell viability detection indicated that mi R-29 a transfection had no adverse effect on the host cells. Moreover, SMARCE1 was identified and validated to be a functional target of mi R-29 a. Furthermore, restored expression of SMARCE1 could relieve the increased HBV replication and expression caused by mi R-29 a overexpression.CONCLUSION mi R-29 a promotes HBV replication and expression through regulating SMARCE1. As a potential regulator of HBV replication and expression, mi R-29 a could be a promising therapeutic target for patients with HBV infection.展开更多
It is unclear whether immune escape-associated mutations in the major hydrophilic region of hepatitis B virus surface antigen(HBsAg)are associated with nucleoside/nucleotide analog resistance.AIM To evaluate the assoc...It is unclear whether immune escape-associated mutations in the major hydrophilic region of hepatitis B virus surface antigen(HBsAg)are associated with nucleoside/nucleotide analog resistance.AIM To evaluate the association between immune escape-associated mutations and nucleoside/nucleotide analog resistance mutations.METHODS In total,19440 patients with chronic hepatitis B virus infection,who underwent resistance testing at the Fifth Medical Center of Chinese PLA General Hospital between July 2007 and December 2017,were enrolled.As determined by sequence analysis,6982 patients harbored a virus with resistance mutations and 12458 harbored a virus lacking resistance mutations.Phenotypic analyses were performed to evaluate HBsAg production,replication capacity,and drug-induced viral inhibition of patient-derived drug-resistant mutants with or without the coexistence of sA159V.RESULTS The rate of immune escape-associated mutation was significantly higher in 9 of the 39 analyzed mutation sites in patients with resistance mutations than in patients without resistance mutations.In particular,these mutations were sQ101H/K/R,sS114A/L/T,sT118A/K/M/R/S/V,sP120A/L/Q/S/T,sT/I126A/N/P/S,sM133I/L/T,sC137W/Y,sG145A/R,and sA159G/V.Among these,sA159V was detected in 1.95%(136/6982)of patients with resistance mutations and 1.08%(134/12,458)of patients lacking resistance mutations(P<0.05).The coexistence of sA159V with lamivudine(LAM)and entecavir(ETV)-resistance mutations in the same viral genome was identified during follow-up in some patients with drug resistance.HBsAg production was significantly lower and the replication capacity was significantly higher,without a significant difference in LAM/ETV susceptibility,in sA159V-containing LAM/ETV-resistant mutants than in their sA159V-lacking counterparts.CONCLUSION In summary,we observed a close link between the increase in certain immune escape-associated mutations and the development of resistance mutations.sA159V might increase the fitness of LAM/ETV-resistant mutants under environmental pressure in some cases.展开更多
Global prophylactic vaccination programmes have helped to curb new hepatitis B virus(HBV)infections.However,it is estimated that nearly 300 million people are chronically infected and have a high risk of developing he...Global prophylactic vaccination programmes have helped to curb new hepatitis B virus(HBV)infections.However,it is estimated that nearly 300 million people are chronically infected and have a high risk of developing hepatocellular carcinoma.As such,HBV remains a serious health priority and the development of novel curative therapeutics is urgently needed.Chronic HBV infection has been attributed to the persistence of the covalently closed circular DNA(cccDNA)which establishes itself as a minichromosome in the nucleus of hepatocytes.As the viral transcription intermediate,the cccDNA is responsible for producing new virions and perpetuating infection.HBV is dependent on various host factors for cccDNA formation and the minichromosome is amenable to epigenetic modifications.Two HBV proteins,X(HBx)and core(HBc)promote viral replication by modulating the cccDNA epigenome and regulating host cell responses.This includes viral and host gene expression,chromatin remodeling,DNA methylation,the antiviral immune response,apoptosis,and ubiquitination.Elimination of the cccDNA minichromosome would result in a sterilizing cure;however,this may be difficult to achieve.Epigenetic therapies could permanently silence the cccDNA minichromosome and promote a functional cure.This review explores the cccDNA epigenome,how host and viral factors influence transcription,and the recent epigenetic therapies and epigenome engineering approaches that have been described.展开更多
BACKGROUND Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus(HBV)infections.One of the key elements for HBV-related carcinogenesis is persiste...BACKGROUND Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus(HBV)infections.One of the key elements for HBV-related carcinogenesis is persistent viral replication and inflammation.AIM To examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma(HCC).METHODS The HCC families included 301 hepatitis B surface antigen(HBsAg)carriers and 424 noncarriers born before the nationwide vaccination program was initiated in 1984.Five HBV-related single nucleotide polymorphisms(SNPs)—rs477515,rs9272105,rs9276370,rs7756516,and rs9277535—were genotyped.Factors associated with persistent HBV infection and viral load were analyzed by a generalized estimating equation.RESULTS In the first-stage persistent HBV study,all SNPs except rs9272105 were associated with persistent infection.A significantly higher area under the reciprocal operating characteristic curve for nongenetic factors vs genetic factors(P<0.001)suggests that the former play a major role in persistent HBV infection.In the second-stage viral load study,we added 8 HBsAg carriers born after 1984.The 309 HBsAg carriers were divided into low(n=162)and high viral load(n=147)groups with an HBV DNA cutoff of 105 cps/mL.Sex,relationship to the index case,rs477515,rs9272105,and rs7756516 were associated with viral load.Based on the receiver operating characteristic curve analysis,genetic and nongenetic factors affected viral load equally in the HCC family cohort(P=0.3117).CONCLUSION In these east Asian adults,the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.展开更多
BACKGROUND Hepatitis B virus(HBV)nucleos(t)ide analog(NA)therapy reduces liver disease but requires prolonged therapy to achieve hepatitis B surface antigen(HBsAg)loss.There is limited North American real-world data u...BACKGROUND Hepatitis B virus(HBV)nucleos(t)ide analog(NA)therapy reduces liver disease but requires prolonged therapy to achieve hepatitis B surface antigen(HBsAg)loss.There is limited North American real-world data using non-invasive tools for fibrosis assessment and few have compared 1st generation NA or lamivudine(LAM)to tenofovir disoproxil fumarate(TDF).AIM To assess impact of NA on virological response and fibrosis regression using liver stiffness measurement(LSM)(i.e.,FibroScan®).METHODS Retrospective,observational cohort study from the Canadian HBV Network.Data collected included demographics,NA,HBV DNA,alanine aminotransferase(ALT),and LSM.Patients were HBV monoinfected patients,treatment naïve,and received 1 NA with minimum 1 year follow-up.RESULTS In 465(median 49 years,37%female,35%hepatitis B e antigen+at baseline,84%Asian,6%White,and 9%Black).Percentage of 64(n=299)received TDF and 166 were LAM-treated with similar median duration of 3.9 and 3.7 years,respectively.The mean baseline LSM was 11.2 kPa(TDF)vs 8.3 kPa(LAM)(P=0.003).At 5-year follow-up,the mean LSM was 7.0 kPa in TDF vs 6.7 kPa in LAM(P=0.83).There was a significant difference in fibrosis regression between groups(i.e.,mean-4.2 kPa change in TDF and-1.6 kPa in LAM,P<0.05).The last available data on treatment showed that all had normal ALT,but more TDF patients were virologically suppressed(<10 IU/mL)(n=170/190,89%)vs LAM-treated(n=35/58,60%)(P<0.05).None cleared HBsAg.CONCLUSION In this real-world North American study,approximately 5 years of NA achieves liver fibrosis regression rarely leads to HBsAg loss.展开更多
BACKGROUND The hepatitis B virus(HBV)infection is a global public health concern that affects about 2 billion people and causes 1 million people deaths yearly.HBV is a bloodborne disease and healthcare workers(HCWs)ar...BACKGROUND The hepatitis B virus(HBV)infection is a global public health concern that affects about 2 billion people and causes 1 million people deaths yearly.HBV is a bloodborne disease and healthcare workers(HCWs)are a high-risk group because of occupational hazard to patients’blood.Different regions of the world show a highly variable proportion of HCWs infected and/or immunized against HBV.Global data on serologic markers of HBV infection and immunization in HCWs are very important to improve strategies for HBV control.AIM To determine the worldwide prevalence of HBV serological markers among HCWs.METHODS In this systematic review and meta–analyses,we searched PubMed and Excerpta Medica Database(Embase)to identify studies published between 1970 and 2019 on the prevalence of HBV serological markers in HCWs worldwide.We also manually searched for references of relevant articles.Four independent investigators selected studies and included those on the prevalence of each of the HBV serological markers including hepatitis B surface antigen(HBsAg),hepatitis e antigen(HBeAg),immunoglobulin M anti-HBc,and anti-HBs.Methodological quality of eligible studies was assessed and random-effect model meta-analysis resulted in the pooled prevalence of HBV serological markers HBV infection in HCWs.Heterogeneity(I²)was assessed using theχ²test on Cochran’s Q statistic and H parameters.Heterogeneity’sources were explored through subgroup and metaregression analyses.This study is registered with PROSPERO,number CRD42019137144.RESULTS We reviewed 14059 references,out of which 227 studies corresponding to 448 prevalence data among HCWs(224936 HCWs recruited from 1964 to 2019 in 71 countries)were included in this meta-analysis.The pooled seroprevalences of current HBsAg,current HBeAg,and acute HBV infection among HCWs were 2.3%[95% confidence interval(CI):1.9-2.7],0.2%(95%CI:0.0-1.7),and 5.3%(95%CI:1.4-11.2),respectively.The pooled seroprevalences of total immunity against HBV and immunity acquired by natural HBV infection in HCWs were 56.6%(95%CI:48.7-63.4)and 9.2%(95%CI:6.8-11.8),respectively.HBV infection was more prevalent in HCWs in low-income countries,particularly in Africa.The highest immunization rates against HBV in HCWs were recorded in urban areas and in high-income countries including Europe,the Eastern Mediterranean and the Western Pacific.CONCLUSION New strategies are needed to improve awareness,training,screening,vaccination,post-exposure management and treatment of HBV infection in HCWs,and particularly in low-income regions.展开更多
liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especial...liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.展开更多
Background: Human immunodeficiency virus and hepatitis B and C viruses are endemic in sub- Saharan African countries including Nigeria. Researchers have studied the burden of co-infection of HIV with hepatitis B and h...Background: Human immunodeficiency virus and hepatitis B and C viruses are endemic in sub- Saharan African countries including Nigeria. Researchers have studied the burden of co-infection of HIV with hepatitis B and hepatitis C but the risk factors and clinical presentation have not been much addressed especially in children. Methodology: This was a prospective cross sectional study that determined the prevalence, risk factors, clinical features, baseline CD4<sup>+</sup> count, CD4<sup>+</sup> percentage, and alanine aminotransferase (ALT) of newly diagnosed, HAART na?ve HIV co-infection among children who were managed at a Tertiary Hospital in Ilorin, Nigeria. Result: Of the 60 HIV- infected children recruited, 11.7% had HIV co-infection with HBV or HCV. Children with co-infec- tions (mean age 8.43 ± 2.37 years) were significantly older than their HIV mono-infected counterparts (mean age 5.25 ± 3.96 years) (p = 0.011). There was no significant difference between HIV monoinfection and HIV co-infection with respect to gender (p = 0.758), ethnicity (p = 0.707), religion of parents (p = 0.436), family type (p = 0.184), social class (p = 0.535), previous transfusion (p = 0.053), scarification (p = 0.612), female genital mutilation (p = 0.778), and sharing of clippers (p = 0.806). The mean BMI, immunological staging (p = 0.535), baseline ALT (p = 0.940), and mean baseline CD4<sup>+</sup> count (p = 0.928) were comparable. However, the body mass index of HIV co-infec- ted children decreased with age up till age 10 years. Conclusion: There were no risk factors, nor clinical features predictive of co-infection identified in this study. Co-infection did not negatively impact baseline, CD4<sup>+</sup> count and ALT.展开更多
Nucleos(t)ide analogs(NUC)are the first-line therapy for patients with chronic hepatitis B(CHB)recommended by most current guidelines.NUC therapy decreases progression of liver disease,reduces the risk of liver-relate...Nucleos(t)ide analogs(NUC)are the first-line therapy for patients with chronic hepatitis B(CHB)recommended by most current guidelines.NUC therapy decreases progression of liver disease,reduces the risk of liver-related complications,and improves the quality of life of patients with CHB.Although indefinite or long-term NUC therapy is usually recommended,this strategy raises several concerns,such as side-effects,adherence,costs,and patient willingness to stop therapy.Recent data showed the feasibility,efficacy,and safety of stopping antiviral therapy in carefully selected CHB patients,leading to its incorporation in international guidelines.Patients who discontinue NUC have a higher likelihood of hepatitis B surface antigen(HBsAg)loss compared to patients who continue on therapy.Recommendations pertaining endpoints allowing safety discontinuation of NUC therapy differ among international guidelines.For hepatitis B e antigen(HBeAg)-positive patients,durable HBeAg seroconversion is considered an acceptable treatment endpoint.For HBeAg-negative patients,some guidelines propose undetectability hepatitis B virus DNA for at least 2 or 3 years,while others consider HBsAg loss as the only acceptable endpoint.CHB patients who stop therapy should remain under strict clinical and laboratorial follow-up protocols to detect and manage relapses in a timely manner.No reliable predictor of relapse has been consistently identified to date,although quantitative HBsAg has been increasingly studied as a reliable biomarker to predict safe NUC discontinuation.展开更多
BACKGROUND The recent rise in the incidence of hepatitis B virus(HBV)infections in a densely populated city of eastern India(“mixing vessel”of people of varied socioeconomic and immune status)prompted this study.App...BACKGROUND The recent rise in the incidence of hepatitis B virus(HBV)infections in a densely populated city of eastern India(“mixing vessel”of people of varied socioeconomic and immune status)prompted this study.Applying saliva on fingers for enumerating bank notes is a common practice in the Indian subcontinent.Paper notes may be a potential source of“horizontal”transmission of this virus,especially if there are cuts/bruises on the oral mucous membrane or skin.AIM To investigate whether paper currencies could be a plausible mode of horizontal transmission of HBV infection.METHODS Polymerase chain reactions(PCR)followed by nucleotide sequencing was done for the detection of HBV.Hepatitis B virus surface antigen enzyme-linked immunosorbent assay(HBsAg ELISA)was performed on all HBV deoxyribonucleic acid-positive samples to check the detectability of the virus.Atomic force microscopy(AFM)was carried out for visual confirmation of HBV particles in ultracentrifuged/immunoprecipitated samples from currency paper washings.RESULTS HBV-specific PCRs on pellets obtained after ultracentrifugation/immunoprecipitation of the currency paper washings detected potentially intact/viable HBV(genotype D2)in 7.14%of samples(n=70).AFM gave the visual confirmation of HBV particles in ultracentrifuged/immunoprecipitated samples from currency paper washings.However,HBV isolates from the currency notes could not be detected by HBsAg ELISA.CONCLUSION It is a common practice in the Indian subcontinent to count paper currencies by applying saliva on fingertips.Paper notes may be a potential source of“horizontal”transmission of this virus,especially if there are cuts/bruises on the oral mucous membrane or skin,but it was practically not possible to demonstrate experimentally such transmission.Detection of potentially intact/viable and“occult”HBV from currency poses potential risk of silent transmission of this virus among the general population.展开更多
Viral hepatitis is a global threat to public health and one of the leading causes of death worldwide.Often,acute viral cases in children and adults are associated with viral hepatitis A,B,C,D and E,or co-infection wit...Viral hepatitis is a global threat to public health and one of the leading causes of death worldwide.Often,acute viral cases in children and adults are associated with viral hepatitis A,B,C,D and E,or co-infection with two types of hepatitis.Infection with these viruses is a global health problem and continuous efforts are in place to identify infected people through targeted screening,preventing new infections through vaccination,monitoring and treating people at risk for complications of all types of hepatitis.The aim of this study was to determine the evaluate the prevalence and trends of hepatitis B and C infection in the Nahavand city during 5 consecutive years(2013–2017).The total number of patients with hepatitis B and C was 141 persons from March 2013 to March 2017,of these,101 had hepatitis B,and 40 had hepatitis C.The prevalence of hepatitis B and C was higher in men than women.The percentage frequency hepatitis B in the city in the last five years was 0.05 percent.11 cases(10.89%)pregnant women and Six cases(5.9%)receiving blood(blood transfusions)in Hepatitis B was observed.the prevalence of hepatitis C was 0.2%at the end of 2017.The study on the cause of hepatitis C in Nahavand has shown that 21(52.5%)of the total of 40 people were infected with addiction.The interesting point in this report is that according to reports from viral hepatitis testing questionnaires,24 of 101 people with type B hepatitis have 23.7%of people with a history of complete vaccination of hepatitis B and one person(0.9%)had incomplete vaccination.A significant relationship was found between the level of education and the prevalence of hepatitis(P=0.005).展开更多
Despite relative effectiveness of current hepatitis B therapies,there is still no curative agents available.The new emerging approaches hold promise to achieve cure and loss of hepatitis B surface antigen.Studies or c...Despite relative effectiveness of current hepatitis B therapies,there is still no curative agents available.The new emerging approaches hold promise to achieve cure and loss of hepatitis B surface antigen.Studies or clinical trials investigating new therapies remain small and either focus on patients with low viral load and without hepatotoxic injury or patients with hepatitis D co-infection,which makes it challenging to assess their effectiveness and side effect profile in hepatitis B population.展开更多
The aim of this study was to identify the risk factors of mother-to-child transmission of HBV in positive Ag Hbs pregnant women in Cote d’Ivoire. Methods: This was a transversal prospective study that took place over...The aim of this study was to identify the risk factors of mother-to-child transmission of HBV in positive Ag Hbs pregnant women in Cote d’Ivoire. Methods: This was a transversal prospective study that took place over a period of 7 months (from February 2016 to August 2016) in 2 university hospital and 2 private clinics. We consecutively recruited 91 pregnant women who were positive for HBs Ag in prenatal consultations. For each pregnant woman record included in the study, we provided Socio-demographic (Age, marital status, education level, social rank, gravidity, parity) and biological data (HBs Ag, Anti-HBc Total Ac, Hbe Ag, Ac anti-Hbe Ac, DNA-VHB, Ac anti-HCV Ac, retroviral serology, transaminases). All of these data were collected using a survey sheet developed for the study. Results: The age of our pregnant women HBs positive ranged from 18 years to 44 years with a mean age of 30.10 years. The age group from 20 to 39 years was the most represented with a frequency of 92.31%. Almost of all positive HBs Ag pregnant women was HBe Ag negative, only 3.3% was HBe Ag positive. The viral load above 2000 IU/ml was found in 21 (23.03%) patients. There were 4 co-infected patients, which 3 HBV-HIV and 1 HBV-HCV. Only 19 (20.88%) pregnant HBs Ag positive women were able to bring back the supplementary virological assessment within a period less than one month. Conclusion: According to our work the virologic profile of positive HBs Ag in pregnant women in Cote d’Ivoire is characterized by an important viral replication objectified by a high viral load in about 23% pregnant women, a negativity of HBe antigen in 96.6% of them.展开更多
文摘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.
基金The study was reviewed and approved by the Akdeniz University Clinical Research Institutional Board(approval No.16-012-211).
文摘BACKGROUND Chronic viral B hepatitis(CHB)is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis.Currently,although combinations of different laboratory methods are used in the follow-up and treatment of CHB,the failure of these procedures in some cases has led to the necessity of developing new approaches.In CHB,the intrahepatic expression pattern of viral antigens,including hepatitis B surface antigen(HBsAg),is related to different phases of inflammation.However,many studies have focused on the intracytoplasmic properties of HBsAg staining,and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods.AIM To investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB.METHODS A total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study.Following diagnosis,all patients were treated with entecavir(0.5 mg)and followed up at three-month intervals.The percentage of immunohistochemical HBsAg(p-HBsAg)expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis.The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications.RESULTS A positive correlation between p-HBsAg and serum levels of hepatitis B virus(HBV)DNA and HBsAg was observed(P<0.001).The p-HBsAg value was significantly higher in younger patients than in older patients.When the groups were categorized according to the hepatitis B e antigen(HBeAg)status in HBeAgpositive cases,p-HBsAg was correlated with HBV DNA,hepatitis activity index(HAI)and fibrosis scores(P<0.001).In this group,p-HBsAg and HBsAg expression patterns were also correlated with the viral response(VR)and the serological response(SR)(P<0.001).Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR(P<0.001).In HBeAg-negative patients,although HBsAg expression patterns were correlated with both HAI and fibrosis,no relationship was observed among p-HBsAg,clinicopathological factors and VR.CONCLUSION In pretreatment liver biopsies,the immunohistochemical determination of HBsAg expression by quantitative methods,beyond its distribution within the cell,may be a good predictor of the treatment response,especially in HBeAg-positive cases.
文摘Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28(2%) received the graft from hepatitis B surface antigen positive(HBs Ag)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary nonfunction, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3-and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBs Agpositive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.
基金Supported by Science and Technology Planning Project of Zhejiang Province,No.LGF20H160001.
文摘BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)-positive carrier status and liver cancer has been extensively studied.However,the epigenetic changes that occur during progression from HBsAg-positive carrier status or cirrhosis to liver cancer are unknown.The epigenetic modification of DNA hydroxymethylation is critical in tumor development.Further,5-hydroxymethylcytosine(5hmC)is an important base for DNA demethylation and epigenetic regulation.It is also involved in the assembly of chromosomes and the regulation of gene expression.However,the mechanism of action of 5hmC in HBsAgpositive carriers or patients with cirrhosis who develop liver cancer has not been fully elucidated.AIM To investigate the possible epigenetic mechanism of HBsAg-positive carriers and hepatocellular carcinoma(HCC)progression from cirrhosis.METHODS Forty HBsAg-positive carriers,forty patients with liver cirrhosis,and forty patients with liver cancer admitted to the First People's Hospital of Yongkang between March 2020 and November 2021 were selected as participants.Free DNA was extracted using a cf-DNA kit.cfDNA was extracted by 5hmC DNA sequencing for principal component analysis,the expression profiles of the three groups of samples were detected,and the differentially expressed genes(DEGs)modified by hydroxymethylation were screened.Bioinformatic analysis was used to enrich DEGs,such as in biological pathways.RESULTS A total of 16455 hydroxymethylated genes were identified.Sequencing results showed that 32 genes had significant 5hmC modification differences between HBsAg carriers and liver cancer patients,of which 30 were upregulated and 2 downregulated in patients with HCC compared with HBsAg-positive carriers.Significant 5hmC modification differences between liver cirrhosis and liver cancer patients were identified in 20 genes,of which 17 were upregulated and 3 were downregulated in patients with HCC compared with those with cirrhosis.These genes may have potential loci that are undiscovered or unelucidated,which contribute to the development and progression of liver cancer.Analysis of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes showed that the major signaling pathways involved in the differential genes were biliary secretion and insulin secretion.The analysis of protein interactions showed that the important genes in the protein-protein interaction network were phosphoenolpyruvate carboxykinase and solute carrier family 2.CONCLUSION The occurrence and development of liver cancer involves multiple genes and pathways,which may be potential targets for preventing hepatitis B carriers from developing liver cancer.
文摘Hepatitis B Virus (HBV) infections affect about 400 million people globally and cause about 1.4 million deaths annually. The virus displays high levels of genetic variations/mutations, some of which are immune escape mutants. The prevalence of HBV infection in Kenya is high at about 8%. This study aimed at identifying and characterizing HBV immune escape mutants in Kenya. From 547 HBV sequences available in Kenya in NCBI, and HBVdb databases in July 2021, 120 full sequences were retrieved. The S gene sequences at position 1-225, which included the “a” determinant region of the gene were analyzed using various bioinformatics tools such as Bioedit software, and Emboss Cons. The clinical significance was flagged from the search of peer-reviewed journals. Forty-six HBV-positive blood donor samples were obtained from the Kenya National Blood Transfusion Services without personal identifiers, DNA extracted, and sequenced targeting positions 1 to 520 of S genes. Mutations were similarly identified from seventeen sequences after cleaning and analysis. Out of 120 sequences that were extracted from databases and analyzed, 79 different mutations were identified. Fifteen of them were of clinical importance with an occurrence frequency of at least 5% were obtained. The majority (64.6%, n = 51), with S207N and A194V being most dominant, could result in immune escape and reduced HBsAg detection signals while 24.1% (n = 19) could result in immune escape/reduced HBsAg detection signals and high probability of hepatocellular carcinoma. Most likely to occur on the amino acids Alanine, Lysine, Serine, Asparagine, and Valine in decreasing order. The most dominant genotype was found to be Genotype A (N = 10), while four sequences were Genotype D. In contrast to the in-silico studies, the sequences from HBV samples from blood donors did not demonstrate the presence of S207N and A194V mutations and all the genotypes were type A1. Only two (13.3%) samples showed the same mutations of sK122R and sT143S for both in-silico analysis and actual sequenced samples. This study did not identify G145R mutation which is the commonest mutation within the HBsAg immunodominant “a” determinant that is associated with immune escape. The concordance of mutations in “a” determinant region of HBsAg gene among various studies is minimal. The study identified new mutations (sA194Y, sS207, sA194S, sS207I, sP46A, sA194T, sS207I, sP46R, and sT143P) that had not been published before. Four (20%) of the mutations were clinically significant. These included sS207R, sT143S, sC76F and sK122R.
文摘BACKGROUND Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues(NAs)rarely achieve hepatitis B surface antigen(HBsAg)loss.AIM To evaluate if the addition of pegylated interferon(Peg-IFN)could decrease HBsAg and hepatitis B core-related antigen(HBcrAg)levels and increase HBsAg loss rate in patients under NAs therapy.METHODS Prospective,non-randomized,open-label trial evaluating the combination of Peg-IFN 180μg/week plus NAs during forty-eight weeks vs NAs in monotherapy.Hepatitis B e antigen-negative non-cirrhotic chronic hepatitis B patients of a tertiary hospital,under NAs therapy for at least 2 years and with undetectable viral load,were eligible.Patients with hepatitis C virus,hepatitis D virus or human immunodeficiency virus co-infection and liver transplanted patients were excluded.HBsAg and HBcrAg levels(log10 U/mL)were measured at baseline and during ninety-six weeks.HBsAg loss rate was evaluated in both groups.Adverse events were recorded in both groups.The kinetic of HBsAg for each treatment group was evaluated from baseline to weeks 24 and 48 by the slope of the HBsAg decline(log10 IU/mL/week)using a linear regression model.RESULTS Sixty-five patients were enrolled,61%receiving tenofovir and 33%entecavir.Thirty-six(55%)were included in Peg-IFN-NA group and 29(44%)in NA group.After matching by age and treatment duration,baseline HBsAg levels were comparable between groups(3.1 vs 3.2)(P=0.25).HBsAg levels at weeks 24,48 and 96 declined in Peg-IFN-NA group(-0.26,-0.40 and-0.44)and remained stable in NA group(-0.10,-0.10 and-0.10)(P<0.05).The slope of HBsAg decline in Peg-IFN-NA group(-0.02)was higher than in NA group(-0.00)(P=0.015).HBcrAg levels did not change.Eight(22%)patients discontinued Peg-IFN due to adverse events.The HBsAg loss was achieved in 3(8.3%)patients of the Peg-IFN-NA group and 0(0%)of the NA group.CONCLUSION The addition of Peg-IFN to NAs caused a greater and faster decrease of HBsAg levels compared to NA therapy.Side effects of Peg-IFN can limit its use in clinical practice.
基金Supported by The 13^(th)Five-Year Plan of Ministry of Science and Technology of the People’s Republic of China,No.2017ZX10302201-004-009,and No.2017ZX10203202-003Beijing Municipal Science and Technology Commission of Major Projects,No.D161100002716002,and No.D161100002716003.
文摘BACKGROUND Hepatitis B surface antigen(HBsAg)loss,a functional cure in patients with chronic hepatitis B(CHB)undergoing antiviral therapy,might be an ideal endpoint of antiviral treatment in clinical practice.The factors that contribute to the functional cure remain unclear,and the predictors of functional cure are worth exploring.The concentration and kinetics of soluble programmed death-1(sPD-1)in patients with CHB may play an important role in elucidating the immune response associated with functional cure after nucleos(t)ide analogs therapy.AIM To investigate the factors associated with HBsAg loss and explore the influence of sPD-1 Levels.METHODS This study analyzed the data and samples from patients with CHB who underwent antiviral treatment in a non-interventional observational study conducted at Peking University First Hospital in Beijing(between 2007 and 2019).All patients were followed up:Serum samples were collected every 3 mo during the first year of antiviral treatment and every 6 mo thereafter.Patients with positive hepatitis B e antigen levels at baseline and with available sequential samples who achieved HBsAg loss during antiviral treatment served as the case group.This case group(n=11)was further matched to 44 positive hepatitis B e anti patients without HBsAg loss as controls.The Spearman’s rank correlation test and receiver operating characteristic curves analysis were performed.RESULTS The sPD-1 Levels were higher in patients with HBsAg loss than in those without HBsAg loss from baseline to month 96,and the differences were significant between the groups at baseline(P=0.0136),months 6(P=0.0003),12(P<0.0001),24(P=0.0007),48(P<0.0001),and 96(P=0.0142).After 6 mo of antiviral treatment,the sPD-1 levels were positively correlated with alanine transaminase(ALT)levels(r=0.5103,P=0.0017),and the sPD-1 levels showed apparent correlation with ALT(r=0.6883,P=0.0192)and HBV DNA(r=0.5601,P=0.0703)levels in patients with HBsAg loss.After 12 mo of antiviral treatment,the sPD-1 levels also showed apparent correlation with ALT(r=0.8134,P=0.0042)and HBV DNA(r=0.6832,P=0.0205)levels in patients with HBsAg loss.The sPD-1 levels were negatively correlated with HBsAg levels in all patients after 12 mo of antiviral treatment,especially at 24(r=-0.356,P=0.0497)and 48(r=-0.4783,P=0.0037)mo.After 6 mo of antiviral treatment,the AUC of sPD-1 for HBsAg loss was 0.898(P=0.000),whereas that of HBsAg was 0.617(P=0.419).The cut-off value of sPD-1 was set at 2.34 log pg/mL;the sensitivity and specificity were 100%and 66.7%,respectively.CONCLUSION The sPD-1 levels at 6 mo can predict HBsAg loss after 144 mo of antiviral treatment.
文摘AIM To investigate the functional role and underlying molecular mechanism of mi R-29 a in hepatitis B virus(HBV) expression and replication.METHODS The levels of mi R-29 a and SMARCE1 in HBV-infected Hep G2.2.15 cells were measured by quantitative real-time PCR and western blot analysis. HBV DNA replication was measured by quantitative PCR and Southern blot analysis. The relative levels of hepatitis B surface antigen and hepatitis B e antigen were detected by enzyme-linked immunosorbent assay. The Cell Counting Kit-8(CCK-8) was used to detect the viability of Hep G2.2.15 cells. The relationship between mi R-29 a and SMARCE1 were identified by target prediction and luciferase reporter analysis.RESULTS mi R-29 a promoted HBV replication and expression, w h i le S MA R C E 1 r e p r e s s e d H B V r e p lic a t io n a n d expression. Cell viability detection indicated that mi R-29 a transfection had no adverse effect on the host cells. Moreover, SMARCE1 was identified and validated to be a functional target of mi R-29 a. Furthermore, restored expression of SMARCE1 could relieve the increased HBV replication and expression caused by mi R-29 a overexpression.CONCLUSION mi R-29 a promotes HBV replication and expression through regulating SMARCE1. As a potential regulator of HBV replication and expression, mi R-29 a could be a promising therapeutic target for patients with HBV infection.
基金the National Natural Science Foundation of China,No.81572010,No.81671399,No.81721002 and No.81971329the Capital Health Research and Development of Special Fund Program,No.2016-2-5032and the Beijing Natural Science Foundation No.7172206.
文摘It is unclear whether immune escape-associated mutations in the major hydrophilic region of hepatitis B virus surface antigen(HBsAg)are associated with nucleoside/nucleotide analog resistance.AIM To evaluate the association between immune escape-associated mutations and nucleoside/nucleotide analog resistance mutations.METHODS In total,19440 patients with chronic hepatitis B virus infection,who underwent resistance testing at the Fifth Medical Center of Chinese PLA General Hospital between July 2007 and December 2017,were enrolled.As determined by sequence analysis,6982 patients harbored a virus with resistance mutations and 12458 harbored a virus lacking resistance mutations.Phenotypic analyses were performed to evaluate HBsAg production,replication capacity,and drug-induced viral inhibition of patient-derived drug-resistant mutants with or without the coexistence of sA159V.RESULTS The rate of immune escape-associated mutation was significantly higher in 9 of the 39 analyzed mutation sites in patients with resistance mutations than in patients without resistance mutations.In particular,these mutations were sQ101H/K/R,sS114A/L/T,sT118A/K/M/R/S/V,sP120A/L/Q/S/T,sT/I126A/N/P/S,sM133I/L/T,sC137W/Y,sG145A/R,and sA159G/V.Among these,sA159V was detected in 1.95%(136/6982)of patients with resistance mutations and 1.08%(134/12,458)of patients lacking resistance mutations(P<0.05).The coexistence of sA159V with lamivudine(LAM)and entecavir(ETV)-resistance mutations in the same viral genome was identified during follow-up in some patients with drug resistance.HBsAg production was significantly lower and the replication capacity was significantly higher,without a significant difference in LAM/ETV susceptibility,in sA159V-containing LAM/ETV-resistant mutants than in their sA159V-lacking counterparts.CONCLUSION In summary,we observed a close link between the increase in certain immune escape-associated mutations and the development of resistance mutations.sA159V might increase the fitness of LAM/ETV-resistant mutants under environmental pressure in some cases.
文摘Global prophylactic vaccination programmes have helped to curb new hepatitis B virus(HBV)infections.However,it is estimated that nearly 300 million people are chronically infected and have a high risk of developing hepatocellular carcinoma.As such,HBV remains a serious health priority and the development of novel curative therapeutics is urgently needed.Chronic HBV infection has been attributed to the persistence of the covalently closed circular DNA(cccDNA)which establishes itself as a minichromosome in the nucleus of hepatocytes.As the viral transcription intermediate,the cccDNA is responsible for producing new virions and perpetuating infection.HBV is dependent on various host factors for cccDNA formation and the minichromosome is amenable to epigenetic modifications.Two HBV proteins,X(HBx)and core(HBc)promote viral replication by modulating the cccDNA epigenome and regulating host cell responses.This includes viral and host gene expression,chromatin remodeling,DNA methylation,the antiviral immune response,apoptosis,and ubiquitination.Elimination of the cccDNA minichromosome would result in a sterilizing cure;however,this may be difficult to achieve.Epigenetic therapies could permanently silence the cccDNA minichromosome and promote a functional cure.This review explores the cccDNA epigenome,how host and viral factors influence transcription,and the recent epigenetic therapies and epigenome engineering approaches that have been described.
基金Supported by Chang Gung Memorial Hospital,No.CMRPG3C0701and National Science Council,No.NSC101-2314-B-182A-025-MY3 and No.MOST 107-2314-B-039-059.
文摘BACKGROUND Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus(HBV)infections.One of the key elements for HBV-related carcinogenesis is persistent viral replication and inflammation.AIM To examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma(HCC).METHODS The HCC families included 301 hepatitis B surface antigen(HBsAg)carriers and 424 noncarriers born before the nationwide vaccination program was initiated in 1984.Five HBV-related single nucleotide polymorphisms(SNPs)—rs477515,rs9272105,rs9276370,rs7756516,and rs9277535—were genotyped.Factors associated with persistent HBV infection and viral load were analyzed by a generalized estimating equation.RESULTS In the first-stage persistent HBV study,all SNPs except rs9272105 were associated with persistent infection.A significantly higher area under the reciprocal operating characteristic curve for nongenetic factors vs genetic factors(P<0.001)suggests that the former play a major role in persistent HBV infection.In the second-stage viral load study,we added 8 HBsAg carriers born after 1984.The 309 HBsAg carriers were divided into low(n=162)and high viral load(n=147)groups with an HBV DNA cutoff of 105 cps/mL.Sex,relationship to the index case,rs477515,rs9272105,and rs7756516 were associated with viral load.Based on the receiver operating characteristic curve analysis,genetic and nongenetic factors affected viral load equally in the HCC family cohort(P=0.3117).CONCLUSION In these east Asian adults,the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.
文摘BACKGROUND Hepatitis B virus(HBV)nucleos(t)ide analog(NA)therapy reduces liver disease but requires prolonged therapy to achieve hepatitis B surface antigen(HBsAg)loss.There is limited North American real-world data using non-invasive tools for fibrosis assessment and few have compared 1st generation NA or lamivudine(LAM)to tenofovir disoproxil fumarate(TDF).AIM To assess impact of NA on virological response and fibrosis regression using liver stiffness measurement(LSM)(i.e.,FibroScan®).METHODS Retrospective,observational cohort study from the Canadian HBV Network.Data collected included demographics,NA,HBV DNA,alanine aminotransferase(ALT),and LSM.Patients were HBV monoinfected patients,treatment naïve,and received 1 NA with minimum 1 year follow-up.RESULTS In 465(median 49 years,37%female,35%hepatitis B e antigen+at baseline,84%Asian,6%White,and 9%Black).Percentage of 64(n=299)received TDF and 166 were LAM-treated with similar median duration of 3.9 and 3.7 years,respectively.The mean baseline LSM was 11.2 kPa(TDF)vs 8.3 kPa(LAM)(P=0.003).At 5-year follow-up,the mean LSM was 7.0 kPa in TDF vs 6.7 kPa in LAM(P=0.83).There was a significant difference in fibrosis regression between groups(i.e.,mean-4.2 kPa change in TDF and-1.6 kPa in LAM,P<0.05).The last available data on treatment showed that all had normal ALT,but more TDF patients were virologically suppressed(<10 IU/mL)(n=170/190,89%)vs LAM-treated(n=35/58,60%)(P<0.05).None cleared HBsAg.CONCLUSION In this real-world North American study,approximately 5 years of NA achieves liver fibrosis regression rarely leads to HBsAg loss.
基金Supported by AREF/EDCTP,No.VARIAFRICA-TMA2019PF-2705.
文摘BACKGROUND The hepatitis B virus(HBV)infection is a global public health concern that affects about 2 billion people and causes 1 million people deaths yearly.HBV is a bloodborne disease and healthcare workers(HCWs)are a high-risk group because of occupational hazard to patients’blood.Different regions of the world show a highly variable proportion of HCWs infected and/or immunized against HBV.Global data on serologic markers of HBV infection and immunization in HCWs are very important to improve strategies for HBV control.AIM To determine the worldwide prevalence of HBV serological markers among HCWs.METHODS In this systematic review and meta–analyses,we searched PubMed and Excerpta Medica Database(Embase)to identify studies published between 1970 and 2019 on the prevalence of HBV serological markers in HCWs worldwide.We also manually searched for references of relevant articles.Four independent investigators selected studies and included those on the prevalence of each of the HBV serological markers including hepatitis B surface antigen(HBsAg),hepatitis e antigen(HBeAg),immunoglobulin M anti-HBc,and anti-HBs.Methodological quality of eligible studies was assessed and random-effect model meta-analysis resulted in the pooled prevalence of HBV serological markers HBV infection in HCWs.Heterogeneity(I²)was assessed using theχ²test on Cochran’s Q statistic and H parameters.Heterogeneity’sources were explored through subgroup and metaregression analyses.This study is registered with PROSPERO,number CRD42019137144.RESULTS We reviewed 14059 references,out of which 227 studies corresponding to 448 prevalence data among HCWs(224936 HCWs recruited from 1964 to 2019 in 71 countries)were included in this meta-analysis.The pooled seroprevalences of current HBsAg,current HBeAg,and acute HBV infection among HCWs were 2.3%[95% confidence interval(CI):1.9-2.7],0.2%(95%CI:0.0-1.7),and 5.3%(95%CI:1.4-11.2),respectively.The pooled seroprevalences of total immunity against HBV and immunity acquired by natural HBV infection in HCWs were 56.6%(95%CI:48.7-63.4)and 9.2%(95%CI:6.8-11.8),respectively.HBV infection was more prevalent in HCWs in low-income countries,particularly in Africa.The highest immunization rates against HBV in HCWs were recorded in urban areas and in high-income countries including Europe,the Eastern Mediterranean and the Western Pacific.CONCLUSION New strategies are needed to improve awareness,training,screening,vaccination,post-exposure management and treatment of HBV infection in HCWs,and particularly in low-income regions.
文摘liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.
文摘Background: Human immunodeficiency virus and hepatitis B and C viruses are endemic in sub- Saharan African countries including Nigeria. Researchers have studied the burden of co-infection of HIV with hepatitis B and hepatitis C but the risk factors and clinical presentation have not been much addressed especially in children. Methodology: This was a prospective cross sectional study that determined the prevalence, risk factors, clinical features, baseline CD4<sup>+</sup> count, CD4<sup>+</sup> percentage, and alanine aminotransferase (ALT) of newly diagnosed, HAART na?ve HIV co-infection among children who were managed at a Tertiary Hospital in Ilorin, Nigeria. Result: Of the 60 HIV- infected children recruited, 11.7% had HIV co-infection with HBV or HCV. Children with co-infec- tions (mean age 8.43 ± 2.37 years) were significantly older than their HIV mono-infected counterparts (mean age 5.25 ± 3.96 years) (p = 0.011). There was no significant difference between HIV monoinfection and HIV co-infection with respect to gender (p = 0.758), ethnicity (p = 0.707), religion of parents (p = 0.436), family type (p = 0.184), social class (p = 0.535), previous transfusion (p = 0.053), scarification (p = 0.612), female genital mutilation (p = 0.778), and sharing of clippers (p = 0.806). The mean BMI, immunological staging (p = 0.535), baseline ALT (p = 0.940), and mean baseline CD4<sup>+</sup> count (p = 0.928) were comparable. However, the body mass index of HIV co-infec- ted children decreased with age up till age 10 years. Conclusion: There were no risk factors, nor clinical features predictive of co-infection identified in this study. Co-infection did not negatively impact baseline, CD4<sup>+</sup> count and ALT.
文摘Nucleos(t)ide analogs(NUC)are the first-line therapy for patients with chronic hepatitis B(CHB)recommended by most current guidelines.NUC therapy decreases progression of liver disease,reduces the risk of liver-related complications,and improves the quality of life of patients with CHB.Although indefinite or long-term NUC therapy is usually recommended,this strategy raises several concerns,such as side-effects,adherence,costs,and patient willingness to stop therapy.Recent data showed the feasibility,efficacy,and safety of stopping antiviral therapy in carefully selected CHB patients,leading to its incorporation in international guidelines.Patients who discontinue NUC have a higher likelihood of hepatitis B surface antigen(HBsAg)loss compared to patients who continue on therapy.Recommendations pertaining endpoints allowing safety discontinuation of NUC therapy differ among international guidelines.For hepatitis B e antigen(HBeAg)-positive patients,durable HBeAg seroconversion is considered an acceptable treatment endpoint.For HBeAg-negative patients,some guidelines propose undetectability hepatitis B virus DNA for at least 2 or 3 years,while others consider HBsAg loss as the only acceptable endpoint.CHB patients who stop therapy should remain under strict clinical and laboratorial follow-up protocols to detect and manage relapses in a timely manner.No reliable predictor of relapse has been consistently identified to date,although quantitative HBsAg has been increasingly studied as a reliable biomarker to predict safe NUC discontinuation.
基金Supported by Institutional Grant by Council of Scientific and Industrial Research-Indian Institute of Chemical Biology,Kolkata,No.MLP-118。
文摘BACKGROUND The recent rise in the incidence of hepatitis B virus(HBV)infections in a densely populated city of eastern India(“mixing vessel”of people of varied socioeconomic and immune status)prompted this study.Applying saliva on fingers for enumerating bank notes is a common practice in the Indian subcontinent.Paper notes may be a potential source of“horizontal”transmission of this virus,especially if there are cuts/bruises on the oral mucous membrane or skin.AIM To investigate whether paper currencies could be a plausible mode of horizontal transmission of HBV infection.METHODS Polymerase chain reactions(PCR)followed by nucleotide sequencing was done for the detection of HBV.Hepatitis B virus surface antigen enzyme-linked immunosorbent assay(HBsAg ELISA)was performed on all HBV deoxyribonucleic acid-positive samples to check the detectability of the virus.Atomic force microscopy(AFM)was carried out for visual confirmation of HBV particles in ultracentrifuged/immunoprecipitated samples from currency paper washings.RESULTS HBV-specific PCRs on pellets obtained after ultracentrifugation/immunoprecipitation of the currency paper washings detected potentially intact/viable HBV(genotype D2)in 7.14%of samples(n=70).AFM gave the visual confirmation of HBV particles in ultracentrifuged/immunoprecipitated samples from currency paper washings.However,HBV isolates from the currency notes could not be detected by HBsAg ELISA.CONCLUSION It is a common practice in the Indian subcontinent to count paper currencies by applying saliva on fingertips.Paper notes may be a potential source of“horizontal”transmission of this virus,especially if there are cuts/bruises on the oral mucous membrane or skin,but it was practically not possible to demonstrate experimentally such transmission.Detection of potentially intact/viable and“occult”HBV from currency poses potential risk of silent transmission of this virus among the general population.
文摘Viral hepatitis is a global threat to public health and one of the leading causes of death worldwide.Often,acute viral cases in children and adults are associated with viral hepatitis A,B,C,D and E,or co-infection with two types of hepatitis.Infection with these viruses is a global health problem and continuous efforts are in place to identify infected people through targeted screening,preventing new infections through vaccination,monitoring and treating people at risk for complications of all types of hepatitis.The aim of this study was to determine the evaluate the prevalence and trends of hepatitis B and C infection in the Nahavand city during 5 consecutive years(2013–2017).The total number of patients with hepatitis B and C was 141 persons from March 2013 to March 2017,of these,101 had hepatitis B,and 40 had hepatitis C.The prevalence of hepatitis B and C was higher in men than women.The percentage frequency hepatitis B in the city in the last five years was 0.05 percent.11 cases(10.89%)pregnant women and Six cases(5.9%)receiving blood(blood transfusions)in Hepatitis B was observed.the prevalence of hepatitis C was 0.2%at the end of 2017.The study on the cause of hepatitis C in Nahavand has shown that 21(52.5%)of the total of 40 people were infected with addiction.The interesting point in this report is that according to reports from viral hepatitis testing questionnaires,24 of 101 people with type B hepatitis have 23.7%of people with a history of complete vaccination of hepatitis B and one person(0.9%)had incomplete vaccination.A significant relationship was found between the level of education and the prevalence of hepatitis(P=0.005).
文摘Despite relative effectiveness of current hepatitis B therapies,there is still no curative agents available.The new emerging approaches hold promise to achieve cure and loss of hepatitis B surface antigen.Studies or clinical trials investigating new therapies remain small and either focus on patients with low viral load and without hepatotoxic injury or patients with hepatitis D co-infection,which makes it challenging to assess their effectiveness and side effect profile in hepatitis B population.
文摘The aim of this study was to identify the risk factors of mother-to-child transmission of HBV in positive Ag Hbs pregnant women in Cote d’Ivoire. Methods: This was a transversal prospective study that took place over a period of 7 months (from February 2016 to August 2016) in 2 university hospital and 2 private clinics. We consecutively recruited 91 pregnant women who were positive for HBs Ag in prenatal consultations. For each pregnant woman record included in the study, we provided Socio-demographic (Age, marital status, education level, social rank, gravidity, parity) and biological data (HBs Ag, Anti-HBc Total Ac, Hbe Ag, Ac anti-Hbe Ac, DNA-VHB, Ac anti-HCV Ac, retroviral serology, transaminases). All of these data were collected using a survey sheet developed for the study. Results: The age of our pregnant women HBs positive ranged from 18 years to 44 years with a mean age of 30.10 years. The age group from 20 to 39 years was the most represented with a frequency of 92.31%. Almost of all positive HBs Ag pregnant women was HBe Ag negative, only 3.3% was HBe Ag positive. The viral load above 2000 IU/ml was found in 21 (23.03%) patients. There were 4 co-infected patients, which 3 HBV-HIV and 1 HBV-HCV. Only 19 (20.88%) pregnant HBs Ag positive women were able to bring back the supplementary virological assessment within a period less than one month. Conclusion: According to our work the virologic profile of positive HBs Ag in pregnant women in Cote d’Ivoire is characterized by an important viral replication objectified by a high viral load in about 23% pregnant women, a negativity of HBe antigen in 96.6% of them.
