Serum hepatitis B core-related antigen as a surrogate marker of hepatitis B e antigen seroconversion in chronic hepatitis B

BACKGROUND Quantitative hepatitis B core-related antigen(qHBcrAg)has a better correlation with intrahepatic hepatitis B virus(HBV)covalently closed circular DNA(cccDNA)than HBV DNA or hepatitis B e antigen(HBeAg),but data are still lacking for its clinical application.AIM The aim was to investigate serum qHBcrAg levels in patients with chronic hepatitis B and assess the correlation of serum qHBcrAg with pregenomic RNA(pgRNA),cccDNA,and HBeAg seroconversion.METHODS This study was a secondary analysis of patients who underwent percutaneous liver biopsy between July 2014 and June 2019 in two multicenter randomized controlled clinical trials of peginterferon vs nucleos(t)ide analog(NUC)-based therapy(NCT03509688 and NCT03546530).Serum qHBcrAg,pgRNA,HBV DNA,hepatitis B core antigen,HBeAg,liver cccDNA,and HBV DNA were measured.The correlations of serum qHBcrAg with other biomarkers were analyzed.RESULTS A total of 139 patients were included.The mean qHBcrAg levels were 5.32±1.18 log10 U/mL at baseline and decreased during treatment(all P<0.0001).Serum qHBcrAg levels were positively correlated with pgRNA(r=0.597,P<0.0001)and cccDNA(r=0.527,P<0.0001)levels.The correlation of serum qHBcrAg level and intrahepatic HBV DNA levels at baseline was weak but significant(r=0.399,P<0.0001).HBcrAg predicted HBeAg seroconversion,with areas under the receiver operating characteristics curve of 0.788 at 24 wk and 0.825 at 48 wk.Log HBcrAg at wk 24 and 48 was independently associated with HBeAg seroconversion[odds ratio(OR)=2.402,95%confidence interval(CI):1.314-4.391,P=0.004;OR=3.587,95%CI:1.315-9.784,P=0.013].CONCLUSION Serum HBcrAg levels were correlated with HBV virological markers and could be used to predict HBeAg seroconversion.

Hepatitis B surface antigen and hepatitis B core-related antigen kinetics after adding pegylated-interferon to nucleos(t)ids analogues in hepatitis B e antigen-negative patients

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.

Hepatitis B core-related antigen:Are we near a treatment endpoint?

Different serological and virological markers in chronic hepatitis B patients guide staging of viral infection,and initiation and response to therapy.Due to the persistence of intrahepatic covalently closed circular DNA(cccDNA)in the hepatocyte nucleus,hepatitis B is not curable.Even after undetectable hepatitis B virus DNA levels,the persistence of hepatitis B surface antigen and novel markers such as hepatitis B core-related antigen(HBcrAg)indicate the persistence of intrahepatic cccDNA.In this study,HBcrAg levels at baseline and after 24 and 48 wk of antiviral therapy predicted hepatitis B e antigen seroconversion.Due to the poor sensitivity of assays and detectable levels in HBsAg-negative patients,the long-term utility of HBcrAg needs future research.

On-treatment monitoring of liver fibrosis with serum hepatitis B core-related antigen in chronic hepatitis B

BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.

Hepatitis B core-related antigen reflects viral replication and protein production in chronic hepatitis B patients

Background:Hepatitis B core-related antigen(HBcrAg)is a promising disease-monitoring marker for chronic hepatitis B(CHB).We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables.Methods:One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks.We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen(HBeAg)-positive and HBeAg-negative patients.We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy.Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods.Results:HBeAg-positive patients(n=93)had higher baseline HBcrAg(median 7.4 vs.5.3 log10 U/mL P<0.001)and greater HBcrAg declines(median 1.6 vs.0.9 log10 U/mL P=0.007)than HBeAg-negative patients after 78 weeks of therapy.At baseline,HBcrAg correlated with hepatitis B virus(HBV)DNA in both HBeAg-positive(r=0.641,P<0.001)and-negative patients(r=0.616,P<0.001),with hepatitis B surface antigen(HBsAg)in HBeAg-positive patients(r=0.495,P<0.001),but not with anti-hepatitis B virus core antibody(anti-HBc).Weak correlations existed between HBcrAg,histology activity index(HAI;r=0.232,P=0.025),and Ishak fibrosis score(r=-0.292,P=0.005)in HBeAg-positive patients.At 78 weeks,significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive(r=-0.263,P=0.014)and HBeAg-negative patients(r=-0.291,P=0.045).Decreased HBcrAg significantly correlated with reduced HBV DNA(r=0.366,P=0.001;r=0.626,P<0.001)and HBsAg(r=0.526,P=0.001;r=0.289,P=0.044)in HBeAg-positive and-negative patients,respectively,and with reduced HAI in HBeAg-positive patients(r=0.329,P=0.001).Patients with HBeAg loss(n=29)showed a larger reduction in HBcrAg than those without(median 2.3 vs.1.3 log10 U/mL,P=0.001).In multivariate analysis,decreased HBcrAg was an independent predictor of HBeAg loss(P=0.005).Conclusions:HBcrAg reflects viral replication and protein production.Decreased HBcrAg could predict HBeAg loss after antiviral therapy.Trial registration:Clinical Trials.gov:NCT01962155;https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1.

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

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

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

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

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

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

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

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

Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti

BACKGROUND In endemic areas,vertical transmission of hepatitis B virus(HBV)remains a major source of the global reservoir of infected people.Eliminating mother-to-child transmission(MTCT)of HBV is at the heart of World Health Organization’s goal of reducing the incidence of HBV in children to less than 0.1%by 2030.Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures.AIM To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen(HBsAg)-positive mothers in Djibouti city.METHODS We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants.The study ran from January 2021 to May 2022,and infants were followed up to 7 mo of age.HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay(Biomérieux,Paris,France)and the automated Amplix platform(Biosynex,Strasbourg,France).All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth.These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis.Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response.All statistical analyses were performed with version 4.0.1 of the R software.RESULTS Of the 50 pregnant women recruited,the median age was 31 years,ranging from 18 years to 41 years.The MTCT rate in this cohort was 4%(2/50)in HBsAg-positive women and 67%(2/3)in hepatitis B e antigen-positive women with a viral load>200000 IU/mL.Of the 48 infants who did not fail immunoprophylaxis,8(16%)became poor responders(anti-HB<100 mIU/mL)after HBV vaccination and hepatitis B immunoglobulin,while 40(84%)infants achieved a good level of seroprotection(anti-HB>100 mIU/mL).Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels(>200000 IU/mL)and hepatitis B e antigen-positive status(odds ratio=158,95%confidence interval:5.05-4958,P<0.01).Birth weight<2500 g was associated with a poor immune response to vaccination(odds ratio=34,95%confidence interval:3.01-383.86,P<0.01).CONCLUSION Despite a failure rate of immunoprophylaxis higher than the World Health Organization target,this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV.Therefore,further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.

Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers

AIM:To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B via placenta and its transformation in these babies were investigated. METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B seroiogic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.

Models for predicting hepatitis B e antigen seroconversion in response to interferon-α in chronic hepatitis B patients

AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe Agpositive chronic hepatitis B patients in China and analyzed variables after initiating IFN-α1b treatment.Patients were tested for serum alanine aminotransferase(ALT),hepatitis B virus-DNA,hepatitis B surface antigen(HBs Ag),antibody to hepatitis B surface antigen,HBe Ag,antibody to hepatitis B e antigen(anti-HBe),and antibody to hepatitis B core antigen(anti-HBc)at baseline and 12 wk,24 wk,and 52 wk after initiating treatment.We performed univariate analysis to identify response predictors among the variables.Multivariate models to predict treatment response were constructed at baseline,12 wk,and 24 wk.RESULTS:At baseline,the 3 factors correlating most with HBe Ag seroconversion were serum ALT level>4×the upper limit of normal(ULN),HBe Ag≤500 S/CO,and anti-HBc>11.4 S/CO.At 12 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤250 S/CO,decline in HBe Ag>1 log10 S/CO,and anti-HBc>11.8 S/CO.At 24 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤5 S/CO,anti-HBc>11.4 S/CO,and decline in HBe Ag>2 log10 S/CO.Each variable was assigned a score of1,a score of 0 was given if patients did not have any of the 3 variables.The 3 factors most strongly correlating with HBe Ag seroconversion at each time point were used to build models to predict the outcome after IFN-αtreatment.When the score was 3,the response rates at the 3 time points were 57.7%,83.3%,and 84.0%,respectively.When the score was 0,the response rates were 2.9%,0.0%,and 2.1%,respectively.CONCLUSION:Models with good negative and positive predictive values were developed to calculate the probability of response to IFN-αtherapy.

Clinical utility of hepatitis B surface antigen kinetics in treatment-na?ve chronic hepatitis B patients during longterm entecavir therapy

AIM To investigate the utility of hepatitis B surface antigen(HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment.METHODS This retrospective study included treatment-na?ve chronic hepatitis B patients who received at least 2 years of consecutive entecavir treatment. Patients were followed up at three to six month intervals with liver biochemistry, hepatitis B virus DNA, and abdominal sonography. In hepatitis B e antigen(HBeAg)-positive patients, HBeAg levels were assessed every three to six month until results became negative. Serum HBsAg levels were determined at the baseline, oneyear and five-year time points. Liver cirrhosis was diagnosed through liver biopsy, imaging examinations, or clinical findings of portal hypertension. Hepatocellular carcinoma was diagnosed by histological examination or dynamic image studies.RESULTS A total of 211 patients were enrolled. The median treatment time was 5.24(2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg levels were associated with an earlier virological response, earlier hepatitis B e antigen(HBeAg) seroconversion, and earlier biochemical response in HBeAg-positive patients(cut-off value: 4 log IU/mL) and an earlier virological response in HBeAg-negative non-cirrhotic patients(cut-off value: 2.4 log IU/mL). Although HBsAg levels decreased slowly during long-term entecavir treatment, higher HBsAg decrease rates were found in the first year for HBeAg-positive non-cirrhotic patients, and patients with higher baseline HBsAg levels. More favorable clinical outcomes were not observed by a rapid HBsAg decline per se, but depended on lower baseline HBsAg levels.CONCLUSION Baseline HBsAg can be used to predict treatment responses. HBsAg levels and decrease rates should be considered together according to disease status while interpreting HBsAg changes.

Hepatitis B virus infection:defective surface antigen expression and pathogenesis

Hepatitis B virus(HBV) infection is a global public health concern. HBV causes chronic infection in patients and can lead to liver cirrhosis, hepatocellular carcinoma, and other severe liver diseases. Thus, understanding HBV-related pathogenesis is of particular importance for prevention and clinical intervention. HBV surface antigens are indispensable for HBV virion formation and are useful viral markers for diagnosis and clinical assessment. During chronic HBV infection, HBV genomes may acquire and accumulate mutations and deletions, leading to the expression of defective HBV surface antigens. These defective HBV surface antigens have been found to play important roles in the progression of HBV-associated liver diseases. In this review, we focus our discussion on the nature of defective HBV surface antigen mutations and their contribution to the pathogenesis of fulminant hepatitis B. The relationship between defective surface antigens and occult HBV infection are also discussed.

HBV DNA level and antigen concentration in evaluating liver damage of patients with chronic hepatitis B

OBJECTIVE: To investigate the correlations between HBV DNA levels and viral antigen concentrations in patients with chronic hepatitis B and their significance in clinical practice. METHODS: The HBV DNA levels and serological markers of 118 patients with chronic hepatitis B and 87 patients with liver cirrhosis who had not been treated with antiviral drugs were determined as well as the other parameters relevant to liver function. RESULTS: The HBV DNA levels of the patients with chronic hepatitis anti cirrhosis were expressed as geometric mean±SD, 3.83×10~6±1.34 copies/ml anti 6.98×10~5±1.29 copies/ml, and their HBeAg concentrations expressed as the luminescent values rate of sample to control (s/co) were 35.40±1.26 and 4.05±1.28, respectively. The HBV DNA levels in HBeAg positive group were significantly higher than those in HBeAg negative group (P<0.0001). The correlation coefficient between HBV DNA level and HBeAg or HBsAg concentration was only O. 273 anti -0.12. During the recovery of hepatic function, the reduction of ALT or AST in patients with high viral content was significantly lower than that in patients with low viral content. No correlation was observed between HBV DNA and ALT levels. CONCLUSION: There are significant correlations between HBV DNA level anti HBeAg concentration, but the coefficient is lower. HBV DNA level is not significantly related to ALT, but it could affect the recovery of liver function.

Hepatitis B surface antigen levels during natural history of chronic hepatitis B: A Chinese perspective study

AIM: To determine the baseline hepatitis B surface antigen (HBsAg) levels during the different phases of chronic hepatitis B (CHB) patients in China.

Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL:An observational study

BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.

Relationship of human leukocyte antigen class II genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients

AIM： To study the relationship of human leukocyte antigen （HLA）-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon （IFN） in HBV-infected patients. METHODS： Low-resolution DNA typing kit was used to determine HLA-DR-1 and -DQB1 genes in 72 patients with chronic hepatitis B （CHB） and HLA-DRB1 in 200 healthy people ready to donate their bone marrow in Shanghai. Among CHB patients, 35 were treated with IFNα-1b for 24 wk. RESULTS： The frequencies of HLA-DRBI＊06, DRBI＊08 and DRB1＊16 alleles in 72 patients were higher than in 200 healthy people （2.08% vs0%, OR = 3.837, P= 0.018; 11.11% vs5.50%, OR = 2.148, P= 0.034; and 6.94% vs 3.00%, OR = 0.625, P = 0.049, respectively）; whereas that of DRBI＊07 allele was lower （2.78% vs 7.75%, OR = 0.340, P= 0.046）. The frequency of HLA-DRBI＊ 14 allele was higher in 11 responders to IFN compared with 24 non-responders （18.18% vs2.08%, OR = 10.444, P = 0.031）, whereas that of DQBI＊07 allele was inverse （9.09% vs37.50%, OR = 0.167, P= 0.021）. CONCLUSION： The polymorphism of HLA class II may influence the susceptibility to HBV infection and the response to IFN in studied CHB patients. Compared with other HLA-DRB1 alleles, HLA-DRBI＊06, DRBI＊08, and DRB1＊16 may be associated with chronicity of HBV infection, HLA-DRBI＊07 with protection against HBV infection, and HLA-DRB1＊14 allele may be associated with a high rate of the response of CHB patients to IFN treatment. Compared with other HLA-DQB1 alleles, HLA-DQBI＊07 may be associated with low response rate to IFN. 2005 The WJG Press and Elsevier Inc. All rights reserved

Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a

AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level < 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level(< 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable(< 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations.