AIM: To investigate the biological impacts of 'hot-spot'mutations on genotype B and C HBV X proteins (HBx).METHODS: Five types of'hot-spot' mutations of genotype B or C HBV X genes, which sequentially ...AIM: To investigate the biological impacts of 'hot-spot'mutations on genotype B and C HBV X proteins (HBx).METHODS: Five types of'hot-spot' mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I,I127T+K130M+V131I, or K130M+V131I+F132Y, respectively,were generated by means of site-directed mutagenesis.To evaluate the anti-proliferative effects, HBx or related mutants' expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity,and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVβ to Chang cells, which were lysed 48 h post-transfection and the intra-cellular β-galactosidase activities were monitored (increase of the β-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples t-test.RESULTS: As compared to standard genotype B HBx,mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity,compared to standard genotype C HBx, F132Y and K130M+V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity,while the mutants of I127T and I127T+K130M+V131I showed no differences.CONCLUSION: 'Hot-spot' mutations affect the antiproliferation and transactivation activities of genotype B and/or C HBx, and the biological impacts of most 'hot-spot' mutations on HBx are genotype B and C differentiated.展开更多
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 ...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.展开更多
INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For...INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For example, a statistical data from ahospital in Shanghai showed that 80% of HCCpatients were positive for HBsAg ( personalcommunication).展开更多
Of 350 million people worldwide are chronically infected with hepatitis B virus(HBV)and are at risk of developing cirrhosis and hepatocellular carcinoma(HCC)later in life.HBV is the most diverse DNA virus,and its geno...Of 350 million people worldwide are chronically infected with hepatitis B virus(HBV)and are at risk of developing cirrhosis and hepatocellular carcinoma(HCC)later in life.HBV is the most diverse DNA virus,and its genome is composed of four open reading frames:Presurface antigen/surface antigen gene(preS/S),precore/core gene(preC/C),polymerase gene(P),and theχgene(χ).HBV produces quasispecies naturally or in response to antiviral agents because of the absence of proofreading activity amid reverse transcription and a high replication rate.The virus has 10 genotypes(A to J)with different geographical distributions.There are various HBV mutations in the HBV genome,including preC/C mutations,preS/S mutations,P gene mutations,andχgene mutations.The core promoter region plays a vital part in the replication,morphogenesis and pathogenesis of the virus.The precore region also plays a crucial role in viral replication.Both core promoter and precore mutations rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity.preC/C mutations are associated with liver disease progression.Precore mutations stop hepatitis B e antigen(HBeAg)production and basal core promoter mutations downregulate HBeAg production.Mutations in the basal core promoter are also associated with increased HBV replication and an increased incidence of advanced liver diseases such as cirrhosis and HCC.The emergence of antiviral-resistant mutations is the main reason for treatment failure.This review focuses mainly on preC/C promoter mutations and their correlation with genotypes and liver disease severity.Thorough perception and knowledge of HBV genetic variety and mutants could be vital to discover techniques for the prognosis and control of HBV infection.展开更多
Objective:To assess the knowledge and attitudes of the general population regarding hepatitis B virus(HBV)infection,their association with sociodemographic factors,and the community’s willingness to pay for hepatitis...Objective:To assess the knowledge and attitudes of the general population regarding hepatitis B virus(HBV)infection,their association with sociodemographic factors,and the community’s willingness to pay for hepatitis B vaccination.Methods:This cross-sectional study was conducted from January to March 2025 in Ho Chi Minh City,Vietnam.A self-administered questionnaire was distributed to 1098 adults who were recruited via nonprobability convenience sampling.Descriptive analysis was conducted to calculate the frequencies and percentages of the categorical variables.A Chi-square test was carried out to explore the association between the independent and categorical dependent variables.Results:A total of 926 complete questionnaires were returned and included in the analysis.Among the participants,524(56.6%)exhibited good knowledge about HBV infection and vaccination,while 651(70.3%)showed positive attitudes toward the issues of interest.The factors associated with knowledge and attitudes were household incomes,health insurance,family history of HBV infection,vaccination intention,reasons for nonvaccination,sources of HBV information,and awareness of immunization programs and vaccination sites.Conclusions:Although most participants had limited knowledge of HBV symptoms and transmission,their attitudes toward vaccination remained positive.Targeted national strategies and intervention initiatives are needed since public awareness and attitudes toward the condition greatly impact intervention success.展开更多
OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted...OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted from previously published databases.The autoimmune hepatitis(AIH)-related regulatory genes were obtained from the Dis Ge NET database.Intersections were taken,and enrichment analyses were performed on the extracted data.Concanavalin A(Con A)-induced AIH model mice were treated with CGGD via gavage.The results of network pharmacological analysis were experimentally validated.RESULTS:Network pharmacology revealed 228 genes at the intersection of AIH and CGGD.Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and cellular metabolism in AIH.Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways.As predicted,CGGD attenuated Con A-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway.Histopathological assessment confirmed the protective effects of CGGD against Con Ainduced AIH.Further investigation revealed that CGGD regulated the T helper cell 17(Th17)/regulatory T cell(Treg)balance by modulating the PI3K/Akt/nuclear factor kappa-B(NF-κB)pathway.CONCLUSIONS:This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation.Its mechanism of action involves PI3K/Akt/NF-κB-mediated regulation of Th17/Treg cells.展开更多
BACKGROUND C-X-C chemokine receptor type 5(CXCR5)^(+)CD8^(+)T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell responses.Despi...BACKGROUND C-X-C chemokine receptor type 5(CXCR5)^(+)CD8^(+)T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell responses.Despite their importance,the specific role of CXCR5^(+)CD8^(+)T cells in chronic hepatitis B(CHB),particularly during interferon-alpha(IFN-α)treatment,is not fully understood.This study aims to elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained serologic response(SR)in patients undergoing 48 weeks of pegylated IFN-α(peg-IFN-α)treatment for CHB.AIM To elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-αtreatment for CHB.METHODS This study enrolled 60 patients with hepatitis Be antigen(HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-αtreatment.Participants were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months,HBeAb-negative,hepatitis B virus DNA levels exceeding 2×10^(4) copies/mL,and alanine aminotransferase(ALT)levels between 2 and 10 times the upper limit of normal.Blood samples were collected at baseline and at weeks 12,24,48,and a 24-week treatment-free follow-up(week 72)to measure serum interleukin(IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1(PD-L1)expression on CD8^(+)T cells by flow cytometry,CXCR5 is a chemokine receptor that directs immune cells to specific tissues,while PD-L1 is a protein that regulates immune responses by inhibiting T cell activity.RESULTS Patients with CHB exhibited significantly lower levels of circulating CXCR5^(+)CD8^(+)T cells compared to healthy controls(P<0.01).Notably,CXCR5^(+)CD8^(+)T cells were prominently expressed in patients who achieved sustained SR compared to non-SR(NSR).A significant correlation was observed between CXCR5 and PD-L1 expression(r=-0.189,P=0.002).However,there was no significant correlation between serum IL-21 levels and CXCR5+CD8+lymphocytes(r=-0.03,P=0.625)or serum ALT levels(r=0.026,P=0.678).CONCLUSION The enhanced expression of CXCR5^(+)CD8^(+)T cells in patients achieving HBeAg seroconversion during IFN-αtreatment suggests that these cells play a crucial role in antiviral immune responses against hepatitis B.This study highlights the potential of CXCR5^(+)CD8^(+)T cells as immune regulators in CHB,which may inform future therapeutic strategies to optimize antiviral treatments.展开更多
BACKGROUND Existing assessment systems for chronic hepatitis B(CHB)-associated liver fibrosis(LF)exhibit insufficient accuracy,thereby requiring further improvements.AIM To investigate the association of LF staging wi...BACKGROUND Existing assessment systems for chronic hepatitis B(CHB)-associated liver fibrosis(LF)exhibit insufficient accuracy,thereby requiring further improvements.AIM To investigate the association of LF staging with hepatitis B core antibody(HBcAb),hepatitis B virus DNA(HBV-DNA),and hepatitis B surface antigen(HBsAg)in patients with CHB.METHODS We selected 120 patients with CHB receiving treatment in Hangzhou Linping District First People’s Hospital from January 2020 to June 2024.Participants were allocated into the mild(F0-F1,n=52)and moderate-to-severe groups(F2-F4,n=68)following the rigorous LF staging criteria.HBcAb,HBV-DNA,and HBsAg concentrations were measured.Pearson correlations were employed to examine the correlations of HBcAb with HBV-DNA and HBsAg,whereas Spearman correlation analysis was conducted to identify the associations of the three with LF staging.Receiver operating characteristic(ROC)curves were further used to analyze the performance of these biomarkers in diagnosing LF stages.Furthermore,binary logistic regression analysis was conducted to determine the association of these three with LF progression in CHB.RESULTS Markedly increased HBcAb and notably decreased HBV-DNA and HBsAg were observed in moderate-to-severe cases vs their mild counterparts.A positive correlation was observed between HBV-DNA and HBsAg,whereas both markers were inversely associated with HBcAb.Moreover,LF staging exhibited a significant positive correlation with HBcAb and an inverse connection with HBVDNA and HBsAg.The receiver operating characteristic analysis revealed area under the curve values of 0.715,0.799,and 0.662 for HBcAb,HBV-DNA,and HBsAg in diagnosing LF staging,respectively.Combining these markers improved the area under the curve to 0.851.The final analysis identified HBcAb as promoting fibrosis advancement(odds ratio=2.765),whereas HBVDNA demonstrated protective properties(odds ratio=0.247).CONCLUSION HBcAb is negatively correlated with HBV-DNA and HBsAg but positively associated with LF staging.All three markers are valuable in assessing LF staging,and their combined use presents the highest diagnostic efficacy.Importantly,a high HBcAb/low HBV-DNA profile markedly increased fibrosis progression risks in CHB-affected individuals.展开更多
Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global populat...Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.展开更多
BACKGROUND The interplay between abnormal glucose metabolism and the progression of liver fibrosis in patients with both chronic hepatitis B(CHB)and type 2 diabetes mellitus(T2DM)remains unclear.Previous studies have ...BACKGROUND The interplay between abnormal glucose metabolism and the progression of liver fibrosis in patients with both chronic hepatitis B(CHB)and type 2 diabetes mellitus(T2DM)remains unclear.Previous studies have suggested that the coexistence of these conditions may exacerbate liver inflammation and fibrosis;however,the impacts of dynamic changes in glucose metabolism indicators,hypoglycemic medication regimens,and glycemic control status on liver fibrosis require further elucidation.AIM To explore the effect of glycemic control on hepatic fibrosis in patients with CHB and T2DM.METHODS A total of 420 patients with CHB and T2DM admitted to the Public Health Clinical Center of Chengdu between October 2018 and January 2022 were retrospectively included and classified according to liver stiffness measurement and glycemic control for between-group comparisons.RESULTS Significant differences were observed in the alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase,AST/ALT ratio,total bilirubin,direct bilirubin,diabetes treatment program,and thrombin time values among the liver fibrosis groups(adjusted P<0.05).Significant differences in albumin and gamma-glutamyl transferase levels were observed among the groups categorized by glucose status at admission(adjusted P<0.05).A positive correlation between fasting plasma glucose(FPG)and liver stiffness measurement was found to be mediated by ALT and AST.Fibrinogen and the international normalized ratio were positively correlated with glycated hemoglobin A1c,while the fibrosis-4 score,ALT,AST/ALT ratio,type III procollagen N-terminal peptide,ferritin,and activated partial thromboplastin time were correlated with FPG at admission.Additionally,AST was positively correlated with FPG at discharge(P<0.05).CONCLUSION Specific glucose metabolic parameters,hypoglycemic agents,and glycemic control status markers are associated with hepatic fibrosis in patients with both CHB and T2DM.Close blood glucose monitoring,optimized use of hypoglycemic agents,and continuous maintenance of good glycemic control may slow the progression of liver fibrosis in patients with CHB and T2DM.展开更多
MIM： To investigate the different impact of genotypes E and C on the development of liver cirrhosis （LC） among different age groups of patients with chronic hepatitis （CH-B）.METHODS： We examined the outcome of 1...MIM： To investigate the different impact of genotypes E and C on the development of liver cirrhosis （LC） among different age groups of patients with chronic hepatitis （CH-B）.METHODS： We examined the outcome of 121 patients with CH-B, divided by age and genotype. Univariate analyses were used to compare different groups. The Cox proportional hazard model was employed to evaluate factors affecting the development of LC.RESULTS： In patients 〈 30 years old, there were no significant predictors for development of LC. However, in patients ≥ 30 years old, genotype C was the only significant predictor. In the genotype C group, 8 of 12 patients who progressed to LC were 30-49 years old at initial diagnosis of chronic hepatitis （7 patients were positive for HBeAg）. In the genotype B group, 4 of 8 patients who developed LC were ≥50 years old at initial diagnosis and were HBeAg-negative.CONCLUSION： The rate of development of LC was comparable in patients infected with genotypes B and C when CH-B occurred at 〈 30 years old. However, CH-B patients infected with genotype C showed poor prognosis if they were 30-49 years old and were positive for HBeAg. Age-specific natural course of CH-B should be considered when patients with CH-B are treated with antiviral drugs.展开更多
BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with a...BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with autoimmune hepatitis(AIH)has not been clarified.This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases.This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral(entecavir)with immunosuppression(prednisone+azathioprine)therapy,providing new evidence of the mechanism of this complex disease.CASE SUMMARY A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase>20 upper limit of normal(ULN),total bilirubin:97.20μmol/L,immunoglobulin G(IgG)47.1 g/L(>3×ULN),HDV RNA 1.6×10^(7)copies/mL and liver biopsy showed G3S4.Tenofovir alafenamide combined with prednisone and azathioprine was administered,and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L.Another 58-year-old male complained of pain in the liver area,antinuclear antibody was 1:320,IgG 22.6 g/L(>1.3×ULN),and liver biopsy showed G2S3.Entecavir was administered in combination with prednisone and azathioprine,and after 3 months,liver function returned to normal,and IgG reduced to 14.22 g/L.CONCLUSION Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy,and the study of immunomodulatory mechanisms should be emphasized.展开更多
A 47-year-old man presented with general fatigue and dark urine.The laboratory data showed increased levels of hepatic transaminases.The patient was positive for hepatitis B virus(HBV)markers and negative for antihuma...A 47-year-old man presented with general fatigue and dark urine.The laboratory data showed increased levels of hepatic transaminases.The patient was positive for hepatitis B virus(HBV)markers and negative for antihuman immunodeficiency virus.The HBV-DNA titer was set to 7.7 log copies/mL.The patient was diagnosed with acute hepatitis B.The HBV infection route was obscure.The serum levels of hepatic transaminases decreased to normal ranges without any treatment,but the HBVDNA status was maintained for at least 26 mo,indicating the presence of persistent infection.We isolated HBV from the acute-phase serum and determined the genome sequence.A phylogenetic analysis revealed that the isolated HBV was genotype H.In this patient,the elevated peak level of HBV-DNA and the risk alleles at human genome single nucleotide polymorphisms s3077and rs9277535 in the human leukocyte antigen-DP locus were considered to be risk factors for chronic infection.This case suggests that there is a risk of persistent infection by HBV genotype H following acute hepatitis;further cases of HBV genotype H infection must be identified and characterized.Thus,the complete determination of the HBV genotype may be essential during routine clinical care of acute hepatitis B outpatients.展开更多
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 immu...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.展开更多
An estimated 3%-4%of people are living with the hepatitis B virus(HBV),and without treatment,the risk of developing cirrhosis and hepatocellular cancer(HCC)is an omnipresent threat.Prevention of HCC is a major challen...An estimated 3%-4%of people are living with the hepatitis B virus(HBV),and without treatment,the risk of developing cirrhosis and hepatocellular cancer(HCC)is an omnipresent threat.Prevention of HCC is a major challenge,as the association between viral suppression and HCC risk reduction is multifactorial,involving the progressive depletion of hepatocytes through covalently closed circular DNA integration,as well as the prevention of liver fibrosis and cirrhosis.Despite effective and cheap antiviral treatment capable of suppressing HBV replication and thereby cirrhosis and HCC,the current indications for therapy need revision and more research to expand the gamut and treat more infected people.In this review,we discuss the possible expansion of antiviral treatment in chronic hepatitis B to prevent cirrhosis and,importantly,HCC.展开更多
BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)concentrations,hepatitis B virus(HBV)DNA levels,and hepatic function in individuals with chronic hepatitis B(CHB)remains incompletely characterized...BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)concentrations,hepatitis B virus(HBV)DNA levels,and hepatic function in individuals with chronic hepatitis B(CHB)remains incompletely characterized.AIM To examine the association of serum HBsAg concentrations with HBV DNA levels and hepatic function parameters in patients with CHB.METHODS A total of 110 individuals with CHB admitted to Kunming Third People’s Hospital between January 2023 and January 2025 were enrolled as the observation group,whereas 70 age-and sex-matched healthy individuals served as the control group.Fasting peripheral venous blood(5 mL)was collected from all participants.Serum HBsAg and HBV DNA levels(in the observation group),along with hepatic function markers,including total bilirubin(TBIL),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were measured in both groups.Pearson correlation analysis was used to assess the association between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels in patients with CHB.Receiver operating characteristic(ROC)curve analysis was conducted to determine optimal cutoff values of HBsAg for predicting high viral load(HBV DNA≥10^(5) IU/mL)and significant liver injury(ALT≥2×upper limit of normal[ULN]).RESULTS HBsAg levels differed significantly across CHB phases:Immune tolerance(IT)phase(4.62±1.51 lgIU/mL),immune clearance(IC)phase(3.84±1.16 lgIU/mL),low replication(LR)phase(2.99±0.66 lgIU/mL),and HBV e antigen-negative hepatitis(ENH)phase(3.40±0.69 lgIU/mL).Corresponding HBV DNA levels were highest in the IT phase(7.41±1.83 log copies/mL),followed by the IC phase(6.03±1.92 log copies/mL),ENH phase(3.89±1.23 log copies/mL),and LR phase(2.55±1.00 log copies/mL).All hepatic function parameters in patients with CHB were significantly elevated compared to the healthy controls.Pearson correlation analysis showed significant positive associations between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels.ROC analysis revealed that an HBsAg cutoff>4.09 lgIU/mL predicted HBV DNA≥105 IU/mL(high viral load)with 88.57%sensitivity,78.67%specificity,and an area under the curve(AUC)of 0.868(P<0.001),while a cutoff>4.07 lgIU/mL predicted ALT≥2×ULN(significant liver injury)with 69.70%sensitivity,90.91%specificity,and an AUC of 0.821(P<0.001).CONCLUSION Serum HBsAg,a noninvasive serological marker,holds significant clinical value in CHB management by aiding in the stratification of viral burden and the prediction of hepatic impairment.展开更多
BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is ...BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is controversial.AIM To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection.METHODS A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled.All patients received nucleoside/nucleotide analogues(NAs)therapy,and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis.RESULTS The detection rates of a single mutation of rtS106C,rtH126Y,rtD134E,and rtL269I were 8.21%,3.20%,2.55%and 61.49%in 23718 genotype C patients,and 1.31%,1.76%,0.21%,and 92.33%in 4266 genotype B patients,respectively.The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients,accounting for 0.042%of all patients.These 12 patients had received NA treatments except TDF before testing.Among them,6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations,and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations.Compared with the wild-type(WT)strain,the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%,and TDF susceptibility reduced by less than 2-fold,but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility.Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain.In the clinic,emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment.CONCLUSION HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.展开更多
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 mo...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.展开更多
BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nuc...BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.展开更多
In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most importan...In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.Prevention and treatment of HBV are key measures to reduce complications.At present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a challenge.Anti-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’compliance.We will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.展开更多
基金Supported by the Foundation for the Author of National Excellent Doctoral Dissertation of PR China, No. 200359Fujian Natural Science Key Foundation, No, 2002F005Fujian Science and Technology Innovation Foundation for Young Scientists, No.2001J058
文摘AIM: To investigate the biological impacts of 'hot-spot'mutations on genotype B and C HBV X proteins (HBx).METHODS: Five types of'hot-spot' mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I,I127T+K130M+V131I, or K130M+V131I+F132Y, respectively,were generated by means of site-directed mutagenesis.To evaluate the anti-proliferative effects, HBx or related mutants' expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity,and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVβ to Chang cells, which were lysed 48 h post-transfection and the intra-cellular β-galactosidase activities were monitored (increase of the β-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples t-test.RESULTS: As compared to standard genotype B HBx,mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity,compared to standard genotype C HBx, F132Y and K130M+V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity,while the mutants of I127T and I127T+K130M+V131I showed no differences.CONCLUSION: 'Hot-spot' mutations affect the antiproliferation and transactivation activities of genotype B and/or C HBx, and the biological impacts of most 'hot-spot' mutations on HBx are genotype B and C differentiated.
基金Supported by The Chongqing Talents Project,No.cstc2021ycjh-bgzxm0150The First Batch of Key Disciplines on Public Health in Chongqing,The Health Commission of Chongqing,No.2022(72)+1 种基金The Remarkable Innovation-Clinical Research Project,The Second Affiliated Hospital of Chongqing Medical UniversityThe Scientific and Technological Research Program of Chongqing Municipal Education Commission,the Second Affiliated Hospital of Chongqing Medical University,No.KJZD-K202300404.
文摘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.
基金This work was supported by Projects of Tackling Key Problems in ScienceTechnology from the State Science+2 种基金Technology Ministry (TJ99-LA01) Shanghai ScienceTechnology Commission (994919033 )
文摘INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For example, a statistical data from ahospital in Shanghai showed that 80% of HCCpatients were positive for HBsAg ( personalcommunication).
文摘Of 350 million people worldwide are chronically infected with hepatitis B virus(HBV)and are at risk of developing cirrhosis and hepatocellular carcinoma(HCC)later in life.HBV is the most diverse DNA virus,and its genome is composed of four open reading frames:Presurface antigen/surface antigen gene(preS/S),precore/core gene(preC/C),polymerase gene(P),and theχgene(χ).HBV produces quasispecies naturally or in response to antiviral agents because of the absence of proofreading activity amid reverse transcription and a high replication rate.The virus has 10 genotypes(A to J)with different geographical distributions.There are various HBV mutations in the HBV genome,including preC/C mutations,preS/S mutations,P gene mutations,andχgene mutations.The core promoter region plays a vital part in the replication,morphogenesis and pathogenesis of the virus.The precore region also plays a crucial role in viral replication.Both core promoter and precore mutations rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity.preC/C mutations are associated with liver disease progression.Precore mutations stop hepatitis B e antigen(HBeAg)production and basal core promoter mutations downregulate HBeAg production.Mutations in the basal core promoter are also associated with increased HBV replication and an increased incidence of advanced liver diseases such as cirrhosis and HCC.The emergence of antiviral-resistant mutations is the main reason for treatment failure.This review focuses mainly on preC/C promoter mutations and their correlation with genotypes and liver disease severity.Thorough perception and knowledge of HBV genetic variety and mutants could be vital to discover techniques for the prognosis and control of HBV infection.
基金funded by Vietnam National University Ho Chi Minh City(VNU-HCM)under grant number 36-2025-44-02.
文摘Objective:To assess the knowledge and attitudes of the general population regarding hepatitis B virus(HBV)infection,their association with sociodemographic factors,and the community’s willingness to pay for hepatitis B vaccination.Methods:This cross-sectional study was conducted from January to March 2025 in Ho Chi Minh City,Vietnam.A self-administered questionnaire was distributed to 1098 adults who were recruited via nonprobability convenience sampling.Descriptive analysis was conducted to calculate the frequencies and percentages of the categorical variables.A Chi-square test was carried out to explore the association between the independent and categorical dependent variables.Results:A total of 926 complete questionnaires were returned and included in the analysis.Among the participants,524(56.6%)exhibited good knowledge about HBV infection and vaccination,while 651(70.3%)showed positive attitudes toward the issues of interest.The factors associated with knowledge and attitudes were household incomes,health insurance,family history of HBV infection,vaccination intention,reasons for nonvaccination,sources of HBV information,and awareness of immunization programs and vaccination sites.Conclusions:Although most participants had limited knowledge of HBV symptoms and transmission,their attitudes toward vaccination remained positive.Targeted national strategies and intervention initiatives are needed since public awareness and attitudes toward the condition greatly impact intervention success.
基金Supported by the Nanjing Health Science and Technology Key Medical Science and Technology Development Program:Mechanism of Action of the Modified Si-Miao Powder with Sanguisorba Carbonisata in Regulating Microbiota and Microecology for the Treatment of Recurrent Vulvovaginal Candidiasis(ZKX22039)。
文摘OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted from previously published databases.The autoimmune hepatitis(AIH)-related regulatory genes were obtained from the Dis Ge NET database.Intersections were taken,and enrichment analyses were performed on the extracted data.Concanavalin A(Con A)-induced AIH model mice were treated with CGGD via gavage.The results of network pharmacological analysis were experimentally validated.RESULTS:Network pharmacology revealed 228 genes at the intersection of AIH and CGGD.Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and cellular metabolism in AIH.Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways.As predicted,CGGD attenuated Con A-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway.Histopathological assessment confirmed the protective effects of CGGD against Con Ainduced AIH.Further investigation revealed that CGGD regulated the T helper cell 17(Th17)/regulatory T cell(Treg)balance by modulating the PI3K/Akt/nuclear factor kappa-B(NF-κB)pathway.CONCLUSIONS:This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation.Its mechanism of action involves PI3K/Akt/NF-κB-mediated regulation of Th17/Treg cells.
基金Supported by Changsha Science and Technology Program,No.kq2022397Natural Science Foundation of Hunan Province(Departmental Joint Fund),No.2023JJ60440+2 种基金Research Program of Health Commission of Hunan Province,No.202303088786Clinical Medical Research Center for Viral Hepatitis of Hunan Province,No.2023SK4009the Scientific Research Program of FuRong Laboratory,No.2023SK2108.
文摘BACKGROUND C-X-C chemokine receptor type 5(CXCR5)^(+)CD8^(+)T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell responses.Despite their importance,the specific role of CXCR5^(+)CD8^(+)T cells in chronic hepatitis B(CHB),particularly during interferon-alpha(IFN-α)treatment,is not fully understood.This study aims to elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained serologic response(SR)in patients undergoing 48 weeks of pegylated IFN-α(peg-IFN-α)treatment for CHB.AIM To elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-αtreatment for CHB.METHODS This study enrolled 60 patients with hepatitis Be antigen(HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-αtreatment.Participants were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months,HBeAb-negative,hepatitis B virus DNA levels exceeding 2×10^(4) copies/mL,and alanine aminotransferase(ALT)levels between 2 and 10 times the upper limit of normal.Blood samples were collected at baseline and at weeks 12,24,48,and a 24-week treatment-free follow-up(week 72)to measure serum interleukin(IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1(PD-L1)expression on CD8^(+)T cells by flow cytometry,CXCR5 is a chemokine receptor that directs immune cells to specific tissues,while PD-L1 is a protein that regulates immune responses by inhibiting T cell activity.RESULTS Patients with CHB exhibited significantly lower levels of circulating CXCR5^(+)CD8^(+)T cells compared to healthy controls(P<0.01).Notably,CXCR5^(+)CD8^(+)T cells were prominently expressed in patients who achieved sustained SR compared to non-SR(NSR).A significant correlation was observed between CXCR5 and PD-L1 expression(r=-0.189,P=0.002).However,there was no significant correlation between serum IL-21 levels and CXCR5+CD8+lymphocytes(r=-0.03,P=0.625)or serum ALT levels(r=0.026,P=0.678).CONCLUSION The enhanced expression of CXCR5^(+)CD8^(+)T cells in patients achieving HBeAg seroconversion during IFN-αtreatment suggests that these cells play a crucial role in antiviral immune responses against hepatitis B.This study highlights the potential of CXCR5^(+)CD8^(+)T cells as immune regulators in CHB,which may inform future therapeutic strategies to optimize antiviral treatments.
文摘BACKGROUND Existing assessment systems for chronic hepatitis B(CHB)-associated liver fibrosis(LF)exhibit insufficient accuracy,thereby requiring further improvements.AIM To investigate the association of LF staging with hepatitis B core antibody(HBcAb),hepatitis B virus DNA(HBV-DNA),and hepatitis B surface antigen(HBsAg)in patients with CHB.METHODS We selected 120 patients with CHB receiving treatment in Hangzhou Linping District First People’s Hospital from January 2020 to June 2024.Participants were allocated into the mild(F0-F1,n=52)and moderate-to-severe groups(F2-F4,n=68)following the rigorous LF staging criteria.HBcAb,HBV-DNA,and HBsAg concentrations were measured.Pearson correlations were employed to examine the correlations of HBcAb with HBV-DNA and HBsAg,whereas Spearman correlation analysis was conducted to identify the associations of the three with LF staging.Receiver operating characteristic(ROC)curves were further used to analyze the performance of these biomarkers in diagnosing LF stages.Furthermore,binary logistic regression analysis was conducted to determine the association of these three with LF progression in CHB.RESULTS Markedly increased HBcAb and notably decreased HBV-DNA and HBsAg were observed in moderate-to-severe cases vs their mild counterparts.A positive correlation was observed between HBV-DNA and HBsAg,whereas both markers were inversely associated with HBcAb.Moreover,LF staging exhibited a significant positive correlation with HBcAb and an inverse connection with HBVDNA and HBsAg.The receiver operating characteristic analysis revealed area under the curve values of 0.715,0.799,and 0.662 for HBcAb,HBV-DNA,and HBsAg in diagnosing LF staging,respectively.Combining these markers improved the area under the curve to 0.851.The final analysis identified HBcAb as promoting fibrosis advancement(odds ratio=2.765),whereas HBVDNA demonstrated protective properties(odds ratio=0.247).CONCLUSION HBcAb is negatively correlated with HBV-DNA and HBsAg but positively associated with LF staging.All three markers are valuable in assessing LF staging,and their combined use presents the highest diagnostic efficacy.Importantly,a high HBcAb/low HBV-DNA profile markedly increased fibrosis progression risks in CHB-affected individuals.
基金supported by a grant from the Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project(2019ZB101)。
文摘Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.
基金Supported by Natural Science Foundation of Sichuan Province,No.2023NSFSC0682.
文摘BACKGROUND The interplay between abnormal glucose metabolism and the progression of liver fibrosis in patients with both chronic hepatitis B(CHB)and type 2 diabetes mellitus(T2DM)remains unclear.Previous studies have suggested that the coexistence of these conditions may exacerbate liver inflammation and fibrosis;however,the impacts of dynamic changes in glucose metabolism indicators,hypoglycemic medication regimens,and glycemic control status on liver fibrosis require further elucidation.AIM To explore the effect of glycemic control on hepatic fibrosis in patients with CHB and T2DM.METHODS A total of 420 patients with CHB and T2DM admitted to the Public Health Clinical Center of Chengdu between October 2018 and January 2022 were retrospectively included and classified according to liver stiffness measurement and glycemic control for between-group comparisons.RESULTS Significant differences were observed in the alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase,AST/ALT ratio,total bilirubin,direct bilirubin,diabetes treatment program,and thrombin time values among the liver fibrosis groups(adjusted P<0.05).Significant differences in albumin and gamma-glutamyl transferase levels were observed among the groups categorized by glucose status at admission(adjusted P<0.05).A positive correlation between fasting plasma glucose(FPG)and liver stiffness measurement was found to be mediated by ALT and AST.Fibrinogen and the international normalized ratio were positively correlated with glycated hemoglobin A1c,while the fibrosis-4 score,ALT,AST/ALT ratio,type III procollagen N-terminal peptide,ferritin,and activated partial thromboplastin time were correlated with FPG at admission.Additionally,AST was positively correlated with FPG at discharge(P<0.05).CONCLUSION Specific glucose metabolic parameters,hypoglycemic agents,and glycemic control status markers are associated with hepatic fibrosis in patients with both CHB and T2DM.Close blood glucose monitoring,optimized use of hypoglycemic agents,and continuous maintenance of good glycemic control may slow the progression of liver fibrosis in patients with CHB and T2DM.
文摘MIM： To investigate the different impact of genotypes E and C on the development of liver cirrhosis （LC） among different age groups of patients with chronic hepatitis （CH-B）.METHODS： We examined the outcome of 121 patients with CH-B, divided by age and genotype. Univariate analyses were used to compare different groups. The Cox proportional hazard model was employed to evaluate factors affecting the development of LC.RESULTS： In patients 〈 30 years old, there were no significant predictors for development of LC. However, in patients ≥ 30 years old, genotype C was the only significant predictor. In the genotype C group, 8 of 12 patients who progressed to LC were 30-49 years old at initial diagnosis of chronic hepatitis （7 patients were positive for HBeAg）. In the genotype B group, 4 of 8 patients who developed LC were ≥50 years old at initial diagnosis and were HBeAg-negative.CONCLUSION： The rate of development of LC was comparable in patients infected with genotypes B and C when CH-B occurred at 〈 30 years old. However, CH-B patients infected with genotype C showed poor prognosis if they were 30-49 years old and were positive for HBeAg. Age-specific natural course of CH-B should be considered when patients with CH-B are treated with antiviral drugs.
基金Supported by Xinjiang“Tianshan Talents”Medical and Health High-Level Talent Training Program-Young and Middle-Aged Backbone Medical Talents.
文摘BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with autoimmune hepatitis(AIH)has not been clarified.This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases.This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral(entecavir)with immunosuppression(prednisone+azathioprine)therapy,providing new evidence of the mechanism of this complex disease.CASE SUMMARY A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase>20 upper limit of normal(ULN),total bilirubin:97.20μmol/L,immunoglobulin G(IgG)47.1 g/L(>3×ULN),HDV RNA 1.6×10^(7)copies/mL and liver biopsy showed G3S4.Tenofovir alafenamide combined with prednisone and azathioprine was administered,and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L.Another 58-year-old male complained of pain in the liver area,antinuclear antibody was 1:320,IgG 22.6 g/L(>1.3×ULN),and liver biopsy showed G2S3.Entecavir was administered in combination with prednisone and azathioprine,and after 3 months,liver function returned to normal,and IgG reduced to 14.22 g/L.CONCLUSION Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy,and the study of immunomodulatory mechanisms should be emphasized.
基金Supported by Japan Society for the Promotion of Science and the Ministry of Health,Labour and Welfare and the Ministry of Education,Culture,Sports,Science and Technology of Japan
文摘A 47-year-old man presented with general fatigue and dark urine.The laboratory data showed increased levels of hepatic transaminases.The patient was positive for hepatitis B virus(HBV)markers and negative for antihuman immunodeficiency virus.The HBV-DNA titer was set to 7.7 log copies/mL.The patient was diagnosed with acute hepatitis B.The HBV infection route was obscure.The serum levels of hepatic transaminases decreased to normal ranges without any treatment,but the HBVDNA status was maintained for at least 26 mo,indicating the presence of persistent infection.We isolated HBV from the acute-phase serum and determined the genome sequence.A phylogenetic analysis revealed that the isolated HBV was genotype H.In this patient,the elevated peak level of HBV-DNA and the risk alleles at human genome single nucleotide polymorphisms s3077and rs9277535 in the human leukocyte antigen-DP locus were considered to be risk factors for chronic infection.This case suggests that there is a risk of persistent infection by HBV genotype H following acute hepatitis;further cases of HBV genotype H infection must be identified and characterized.Thus,the complete determination of the HBV genotype may be essential during routine clinical care of acute hepatitis B outpatients.
文摘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.
文摘An estimated 3%-4%of people are living with the hepatitis B virus(HBV),and without treatment,the risk of developing cirrhosis and hepatocellular cancer(HCC)is an omnipresent threat.Prevention of HCC is a major challenge,as the association between viral suppression and HCC risk reduction is multifactorial,involving the progressive depletion of hepatocytes through covalently closed circular DNA integration,as well as the prevention of liver fibrosis and cirrhosis.Despite effective and cheap antiviral treatment capable of suppressing HBV replication and thereby cirrhosis and HCC,the current indications for therapy need revision and more research to expand the gamut and treat more infected people.In this review,we discuss the possible expansion of antiviral treatment in chronic hepatitis B to prevent cirrhosis and,importantly,HCC.
文摘BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)concentrations,hepatitis B virus(HBV)DNA levels,and hepatic function in individuals with chronic hepatitis B(CHB)remains incompletely characterized.AIM To examine the association of serum HBsAg concentrations with HBV DNA levels and hepatic function parameters in patients with CHB.METHODS A total of 110 individuals with CHB admitted to Kunming Third People’s Hospital between January 2023 and January 2025 were enrolled as the observation group,whereas 70 age-and sex-matched healthy individuals served as the control group.Fasting peripheral venous blood(5 mL)was collected from all participants.Serum HBsAg and HBV DNA levels(in the observation group),along with hepatic function markers,including total bilirubin(TBIL),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were measured in both groups.Pearson correlation analysis was used to assess the association between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels in patients with CHB.Receiver operating characteristic(ROC)curve analysis was conducted to determine optimal cutoff values of HBsAg for predicting high viral load(HBV DNA≥10^(5) IU/mL)and significant liver injury(ALT≥2×upper limit of normal[ULN]).RESULTS HBsAg levels differed significantly across CHB phases:Immune tolerance(IT)phase(4.62±1.51 lgIU/mL),immune clearance(IC)phase(3.84±1.16 lgIU/mL),low replication(LR)phase(2.99±0.66 lgIU/mL),and HBV e antigen-negative hepatitis(ENH)phase(3.40±0.69 lgIU/mL).Corresponding HBV DNA levels were highest in the IT phase(7.41±1.83 log copies/mL),followed by the IC phase(6.03±1.92 log copies/mL),ENH phase(3.89±1.23 log copies/mL),and LR phase(2.55±1.00 log copies/mL).All hepatic function parameters in patients with CHB were significantly elevated compared to the healthy controls.Pearson correlation analysis showed significant positive associations between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels.ROC analysis revealed that an HBsAg cutoff>4.09 lgIU/mL predicted HBV DNA≥105 IU/mL(high viral load)with 88.57%sensitivity,78.67%specificity,and an area under the curve(AUC)of 0.868(P<0.001),while a cutoff>4.07 lgIU/mL predicted ALT≥2×ULN(significant liver injury)with 69.70%sensitivity,90.91%specificity,and an AUC of 0.821(P<0.001).CONCLUSION Serum HBsAg,a noninvasive serological marker,holds significant clinical value in CHB management by aiding in the stratification of viral burden and the prediction of hepatic impairment.
基金Supported by The National Natural Science Foundation of China,No.82470632.
文摘BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is controversial.AIM To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection.METHODS A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled.All patients received nucleoside/nucleotide analogues(NAs)therapy,and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis.RESULTS The detection rates of a single mutation of rtS106C,rtH126Y,rtD134E,and rtL269I were 8.21%,3.20%,2.55%and 61.49%in 23718 genotype C patients,and 1.31%,1.76%,0.21%,and 92.33%in 4266 genotype B patients,respectively.The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients,accounting for 0.042%of all patients.These 12 patients had received NA treatments except TDF before testing.Among them,6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations,and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations.Compared with the wild-type(WT)strain,the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%,and TDF susceptibility reduced by less than 2-fold,but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility.Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain.In the clinic,emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment.CONCLUSION HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.
文摘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.
基金Supported by National Natural Science Foundation of China,No.U21A20411.
文摘BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.
基金Supported by the Project of Guizhou Provincial Department of Science and Technology,No.Qiankehechengguo-LC[2024]109.
文摘In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.Prevention and treatment of HBV are key measures to reduce complications.At present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a challenge.Anti-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’compliance.We will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.
