HBsAg levels in HBeAg-positive chronic hepatitis B patients with different immune conditions

AIM:To investigate hepatitis B surface antigen(HBsAg)levels in patients with HBeAg-positive chronic hepatitis B(CHB)and different immune conditions.METHODS:HBeAg-positive CHB patients with different immune conditions were enrolled in this cross-sectional study.These patients were grouped according to the following criteria:immune-tolerant patients,IT group;patients with a mild immune response in the immune clearance phase,IC-Mild group;and patients with a dramatic immune response in the immune clearance phase and exhibiting acute on chronic liver failure(ACLF),ACLF group.All these patients had not previously received antiviral therapy and were enrolled at a pre-settled ratio of2:2:1.Serum HBsAg levels and the correlation between serum HBsAg level and serum hepatitis B virus(HBV)DNA level were evaluated in these groups.RESULTS:In total,180 HBeAg-positive CHB patients[IT group(n=72),IC-Mild group(n=72),and ACLF group(n=36)]were enrolled in this study.The median serum HBsAg levels varied among the groups(P<0.001):IT,4.86 log10IU/mL;IC-Mild,3.97 log10IU/mL;and ACLF,3.57 log10IU/mL.Serum HBsAg level showed a moderate positive correlation with serum HBV-DNA level in the IC-Mild group(r=0.60,P<0.001),but exhibited a weaker correlation in the IT(r=0.52,P<0.001)and ACLF groups(r=0.51,P=0.001).The ratio of HBsAg/HBV DNA did not differ significantly among the IT,IC-Mild,and ACLF groups(medians:0.56,0.55,and 0.56,respectively;P=0.179).CONCLUSION:Serum HBsAg levels varied significantly in HBeAg-positive patients with different immune conditions.These findings may have important implications for understanding the immune clearance of HBV in HBeAg-positive CHB patients.     

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.METHODS: Six hundred and twenty-three hepatitis B virus or un-infected patients not receiving antiviral therapy were analyzed in a cross-sectional study. The CHB patients were classified into five phases: immune-tolerant (IT, n = 108), immune-clearance (IC, n = 161), hepatitis B e antigen negative hepatitis (ENH, n = 149), low-replicative (LR, n = 135), and liver cirrhosis (LC, n = 70). HBsAg was quantified (Abbott ARCHITECT assay) and correlated with hepatitis B virus (HBV) DNA, and serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) in each phase of CHB was also determined.RESULTS: Median HBsAg titers were different in each phase of CHB (P < 0.001): IT (4.85 log₁₀ IU/mL), IC (4.36 log₁₀ IU/mL), ENH (2.95 log₁₀ IU/mL), LR (3.18 log₁₀ IU/mL) and LC (2.69 log₁₀ IU/mL). HBsAg titers were highest in the IT phase and lowest in the LC phase. Serum HBsAg titers showed a strong correlation with HBV viral load in the IC phase (r = 0.683, P < 0.001). No correlation between serum HBsAg level and ALT/AST was observed.CONCLUSION: The mean baseline HBsAg levels differ significantly during the five phases of CHB, providing evidence on the natural history of HBV infection. HBsAg quantification may predict the effects of immune-modulator or oral nucleos(t)ide analogue therapy.     

Exploration of nucleos(t)ide analogs cessation in chronic hepatitis B patients with hepatitis B e antigen loss

BACKGROUNDNucleos(t)ide analogs (NAs) cessation in chronic hepatitis B (CHB) patients remains a matter of debate in clinical practice. Current guidelines recommend that patients with hepatitis B e antigen (HBeAg) seroconversion discontinue NAs after relatively long-term consolidation therapy. However, many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg, even if hepatitis B surface antigen (HBsAg) loss occurs. It remains unclear whether NAs can be discontinued in this subset of patients.AIMTo investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss (without hepatitis B e antibody) after cessation of NAs.METHODSWe studied patients who discontinued NAs after achieving HBeAg loss. The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs. The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves; we confirmed the cut-off value of HBsAg according to a previous study. The log-rank test was used to compare cumulative relapse rates among groups. We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates. Propensity score matching analysis (PSM) was used to balance baseline characteristics between the groups.RESULTSWe included 83 patients with HBeAg loss. The mean age of these patients was 32.1 ± 9.5 years, and the majority was male (67.5%). Thirty-eight patients relapsed, and the cumulative relapse rate at months 3, 6, 12, 24, 36, 60, 120, and 180 were 22.9%, 36.1%, 41.0%, 43.5%, 45.0%, 45.0%, 45.0%, and 52.8%, respectively. Twenty-six (68.4%) patients relapsed in the first 3 mo after NAs cessation, and 35 patients (92.1%) relapsed in the first year after NAs cessation. Consolidation period (≥ 24 mo vs < 24 mo) (HR 0.506, P = 0.043) and HBsAg at cessation (≥ 100 IU/mL vs < 100 IU/mL) (HR 14.869, P = 0.008) were significant predictors in multivariate Cox regression. In the PSM cohort, which included 144 patients, there were lower cumulative relapse rates in patients with HBeAg seroconversion (P = 0.036).CONCLUSIONHBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation, especially in patients with HBsAg at cessation < 100 IU/mL. Careful monitoring, especially in the early stages after cessation, may ensure a favorable outcome.     

Hepatitis B surface antigen seroconversion is associated with favourable long-term clinical outcomes during lamivudine treatment in HBeAg-negative chronic hepatitis B patients

The aims of this study were to assess hepatitis B surface antigen (HBsAg) seroconversion and to determine its impact on the natural course of the disease in patients with HBeAg-negative chronic hepatitis B (CHB) during lamivudine (LMV) treatment. A total of 183 consecutive patients with HBeAg-negative CHB who were treated with LMV were included in the study. Data were retrospectively collected from outpatient visit charts. The primary endpoint was HBsAg seroconversion to anti-HBs. The secondary endpoint was to determine the development of cirrhosis. Loss of HBsAg was confirmed in 10 patients and seroconversion to anti-HBs in nine patients during LMV treatment or after its discontinuation. HBsAg seroconversion was achieved on-treatment in four patients after a median treatment duration of 30 months and off-treatment in the remaining five patients in a median 61 months after LMV discontinuation. The cumulative probability of HBsAg seroconversion increased from 0.6% at 1 year and 1.9% at 5 years to 21.5% at 10 years of LMV during and after LMV treatment. HBsAg clearance was preceded by undetectable serum hepatitis B virus (HBV) DNA. The majority of the patients responding to treatment had undetectable HBV DNA levels at 24 weeks of treatment. The cumulative probability of LMV resistance increased from 2.2% at 1 year to 37.3% at 5 years. No baseline parameter predicting either HBsAg seroconversion or the emergence of LMV resistance was identified. None of the patients with HBsAg seroconversion experienced virological breakthrough or disease progression during the follow-up period. These results indicate that HBsAg seroclearance can occur in patients with HBeAg-negative CHB under LMV therapy and predicts better clinical outcome.     

Hepatitis B surface antigen levels of cessation of nucleos(t)ide analogs associated with virological relapse in hepatitis B surface antigen-negative chronic hepatitis B patients

AIM: To investigate the virological relapse rate in hepatitis B e antigen (HBeAg)-negative patients after antiviral therapy discontinuation and analyze the factors associated with virological relapse.METHODS: Among patients diagnosed with chronic hepatitis B infection between May 2005 and July 2010, 204 were eligible for analysis. The Kaplan-Meier method and log-rank test were used to calculate the cumulative rate of relapse and compare cumulative relapse rates between groups. The Cox proportional hazards regression model was used to evaluate the predictive factor of virological relapse.RESULTS: The 2 and 1 year cumulative risks of virological relapse after antiviral therapy discontinuation were 79.41% (162/204) and 43.82% (71/162), respectively. Multivariate analysis revealed that only post treatment hepatitis B surface antigen (HBsAg) level was associated with virological relapse (P = 0.011). The cumulative risk of virological relapse was higher in the patients with HBsAg levels ≥ 1500 IU/L than in those with HBsAg levels < 1500 IU/L (P = 0.0013). The area under the curve was 0.603 (P = 0.033). The cutoff HBsAg value for predicting virological relapse was 1443 IU/L.CONCLUSION: We found that the virological relapse rate remained high after antiviral therapy discontinuation in the HBeAg-negative patients and that the post treatment HBsAg levels predicted virological relapse.     

Baseline HBsAg predicts response to pegylated interferon-α2b in HBeAg-positive chronic hepatitis B patients

AIM: To evaluate the predictive effect of baseline hepatitis B surface antigen (HBsAg) on response to pegylated interferon (PEG-IFN)-α2b in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.METHODS: This retrospective analysis compared the treatment efficacy of PEG-IFN-α2b alone in 55 HBeAg-positive CHB patients with different baseline HBsAg levels. Serum HBV DNA load was measured at baseline, and at 12, 24 and 48 wk of therapy. Virological response was defined as HBV DNA < 1000 IU/mL. Serum HBsAg titers were quantitatively assayed at baseline, and at 12 and 24 wk.RESULTS: Eighteen patients had baseline HBsAg > 20 000 IU/mL, 26 patients had 1500-20000 IU/mL, and 11 patients had < 1500 IU/mL. Three (16.7%), 11 (42.3%) and seven (63.6%) patients in each group achieved a virological response at week 48, with a significant difference between groups with baseline HBsAg levels > 20000 or < 20000 IU/mL (P = 0.02). Thirteen patients had an HBsAg decline > 0.5 log₁₀ and 30 patients < 0.5 log₁₀ at week 12; and 6 (46.2%) and 10 (33.3%) in each group achieved virological response at week 48, with no significant difference between the two groups (P = 0.502). Eighteen patients had an HBsAg decline > 1.0 log₁₀ and 30 patients < 1.0 log₁₀ at week 24, and 8 (44.4%) and 11 (36.7%) achieved a virological response at week 48, with no significant difference between the two groups (P = 0.762). None of the 16 patients with HBsAg > 20000 IU/mL at week 24 achieved a virological response at week 48.CONCLUSION: Baseline HBsAg level in combination with HBV DNA may become an effective predictor for guiding optimal therapy with PEG-IFN-α2b against HBeAg-positive CHB.     

Quantitation of HBsAg predicts response to entecavir therapy in HBV genotype C patients

AIM:To analysis the factors that predict the response to entecavir therapy in chronic hepatitis patients with hepatitis B virus (HBV) genotype C. METHODS:Fifty patients [hepatitis B e antigen (HBeAg)-negative:HBeAg-positive = 26:24] with HBV genotype C, who received nave entecavir therapy for 2 years, were analyzed. Patients who showed HBV DNA levels ≥ 3.0 log viral copies/mL after 2 years of entecavir therapy were designated as slow-responders, while those that showed 3.0 log copies/mL were termed rapid- responders. Quantitative hepatitis B surface antigen (HBsAg) levels (qHBsAg) were determined by the Architect HBsAg QT immunoassay. Hepatitis B core-related antigen was detected by enzyme immunoassay. Pre-C and Core promoter mutations were determined using by polymerase chain reaction (PCR). Drug-resistance mutations were detected by the PCR-Invader method. RESULTS:At year 2, HBV DNA levels in all patients in the HBeAg-negative group were 3.0 log copies/mL. In contrast, in the HBeAg-positive group, 41.7% were slow-responders, while 58.3% were rapid-responders. No entecavir-resistant mutants were detected in the slow-responders. When the pretreatment factors were compared between the slow-and rapid-responders; the median qHBsAg in the slow-responders was 4.57 log IU/mL, compared with 3.63 log IU/mL in the rapid-responders (P 0.01). When the pretreatment factors predictive of HBV DNA-negative status at year 2 in all 50 patients were analyzed, HBeAg-negative status, low HBV DNA levels, and low qHBsAg levels were significant (P 0.01). Multivariate analysis revealed that the low qHBsAg level was the most significant predictive factor (P = 0.03). CONCLUSION:Quantitation of HBsAg could be a useful indicator to predict response to entecavir therapy.     

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

BACKGROUNDHepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues (NAs) rarely achieve hepatitis B surface antigen (HBsAg) loss.AIMTo 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.METHODSProspective, non-randomized, open-label trial evaluating the combination of Peg-IFN 180 µg/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.RESULTSSixty-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. CONCLUSIONThe 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.     

48 weeks outcome after cessation of nucleos(t)ide analogue therapy in chronic hepatitis B patients

Introduction and objectiveThe aim of the present study was to investigate the significance of serum HBsAg levels in treatment cessation of nucleoside analogues (NAs) in patients with chronic hepatitis B (CHB) infection.MethodsIn 158 CHB patients with long-term NAs treatment, 74 patients were in HBeAg negative and had a HBsAg level <1500 IU/mL, 36 of whom were informed and consented to cease NAs. HBsAg, HBV DNA and liver function were examined in the 1st, 3rd, 6th, 9th and 12th month after treatment cessation.ResultsThe sustained response rate was 88.89% (32/36) within one year after NAs cessation. Sub-group analysis was based on HBsAg levels of patients with NAs cessation, there was no relapse case in 11 patients whose HBsAg <50 IU/mL, and the negative predictive value (NPV) was 100%. Seroconversion of HBsAg occurred in 3 patients. 2 patients from 21 cases whose HBsAg was between 50 IU/mL and 1000 IU/mL relapsed. 2 of 4 patients whose in HBsAg >1000 IU/mL relapsed. HBsAg of patients with a sustained response decreased slowly. In contrast, HBsAg levels increased gradually in relapsed patients, and the increase of HBsAg was precedent to relapses of HBV DNA and ALT. Multivariate analysis suggested that only HBsAg level showed a close correlation with HBV DNA relapses. ROC curve analysis suggested that the increase of HBsAg level in the 3rd and 6th month after NAs cessation had a great predictive value for relapses.ConclusionMonitoring of base line HBsAg level can predict outcomes of NAs cessation in HBeAg-negative chronic hepatitis B. HBsAg <50 IU/mL has higher predictive values of better sustained responses in HBeAg-negative CHB patients.     

血清HBsAg滴度监测对恩替卡韦治疗的HBeAg阳性慢性乙型肝炎患者应答反应的预测价值

目的探讨HBeAg阳性慢性乙型肝炎（CHB）患者血清HBsAg滴度的动态变化对恩替卡韦（ETV）治疗反应的预测价值。方法选择2011年1月～2012年1月在我肝病中心住院及门诊接受ETV（0.5mg/d）治疗的HBeAg阳性CHB患者78例,随访1年。于抗病毒治疗的0、3、6、9和12 m分别收集患者血清,采用化学发光法定量检测各时间点的HBsAg和HBeAg滴度;采用实时荧光定量PCR法检测血清HBV DNA载量;采用Pearson相关分析分析HBsAg与HBV DNA水平相关性,采用受试者工作特征曲线（ROC）预测患者的病毒学应答和确定最佳临界值。结果在78例患者中,69例（88.5%）患者发生病毒学应答（VR）,9例未发生病毒学应答;VR组患者基线ALT水平[（141.8±27.2）IU/ml]与未发生VR患者[（136.2±29.7）IU/ml]比,无统计学意义（t=0.27,P=0.793）;HBV DNA[（6.7±1.0）lg IU/ml]明显低于未发生VR患者[（7.6±0.8）lg IU/ml,t=-2.27,P=0.033];HBsAg滴度与未发生VR患者比,无统计学意义[（3.8±0.6）lg IU/ml对（4.0±0.4）lg IU/ml,t=-1.75,P=0.094）];HBsAg与HBV DNA水平呈正相关（r=0.45,P=0.02）;HBsAg在治疗开始的前3个月下降较快,3个月后下降较缓慢,从基线到治疗3个月时,VR组患者较未发生VR患者HBsAg下降更快[（0.3±0.2）lg IU/ml对（0.2±0.1）lg IU/ml,t=2.245,P=0.035）];在治疗3个月时,lg HBsAg滴度的ROC曲线下面积最大（AUC=0.840,P=0.005）,临界值为3.85 lg IU/ml的Youden指数最大（0.602）,其诊断敏感度为84.2%,特异度为78.7%。结论 ETV治疗3个月时lg HBsAg≤3.85 lg IU/ml可作为预测ETV治疗1年发生病毒学应答的指标。     

Hepatitis B Surface Antigen Quantification across Different Phases of Chronic Hepatitis B Virus Infection Using an Immunoradiometric Assay

Background/AimsQuantification of hepatitis B surface antigen (HBsAg) is an emerging serologic test and may be useful for identifying treatment strategies for chronic hepatitis B (CHB). This study aimed to evaluate HBsAg titers during the natural course of CHB and identify correlations between HBsAg titers and hepatitis B virus (HBV) DNA concentrations across different CHB phases measured using an immunoradiometric assay (IRMA).MethodsCHB phases were defined on the basis of HBV DNA concentrations, the presence of hepatitis B e antigen/antibody (HBeAg/Ab) and serum alanine aminotransferase levels. Serum HBsAg titers and paired HBV DNA concentrations in the different phases of CHB were compared using 627 serum samples.ResultsMean HBsAg titers were significantly higher in the immunotolerant (IT) phase and immunoreactive (IR) HBeAg-positive phase than in the low-replicative (LR) and HBeAg-negative CHB (ENH) states. The correlation between HBsAg titers and HBV DNA concentrations was modest in the IT (n=36, r=0.804, p<0.001) and IR (n=48, r=0.773, p<0.001) phases, and it was poor in the LR state (n=116, r=0.289, p=0.002); however, no significant correlation was observed in the ENH state (n=67, r=0.146, p=0.237) or in the oral nucleos(t)ide analogue-treated group (n=267).ConclusionsHBsAg quantification using IRMA might be useful for discriminating different CHB phases and different stages of chronic liver disease.     

Serum hepatitis B surface antigen levels predict treatment response to nucleos(t)ide analogues

Quantification of hepatitis B surface antigen(HBsAg)has been suggested to be helpful in the management of chronic hepatitis B(CHB)patients.Nucleos(t)ide analogs(NAs)are the therapy of choice for CHB and are used in the majority of CHB patients.NAs are able to induce hepatitis B virus(HBV)viral suppression,normalization of alanine aminotransferase(ALT)levels,and improvement in liver histology.Automated quantitative assays for serum HBsAg have recently become available,facilitating standardized quantification of serum HBsAg.This has led to increased interest in the clinical application of quantitative serum HBsAg for predicting therapeutic response to NAs.Recent studies have shown that a decline in serum HBsAg levels in patients receiving peginterferon may signal successful induction of immune control over HBV,and can therefore be used to predict therapeutic response.NA treatment typically induces a less rapid decline in HBsAg than interferon treatment;it has been estimated that full HBsAg clearance can require decades of NA treatment.However,a rapid HBsAg decline during NA therapy may identify patients who will show clearance of HBsAg.Currently,there is no consensus on the clinical utility of serum HBsAg monitoring for evaluating patient responses to NA therapy.This review focuses on recent findings regarding the potential application of HBsAg quantification in the management of CHB patients receiving NA therapy.     

Hepatitis B surface antigen monitoring and management of chronic hepatitis B

Serum hepatitis B surface antigen (HBsAg) levels reflect intrahepatic hepatitis B virus (HBV) covalently closed circular DNA and may be a valuable addition to HBV DNA in the management of patients with chronic hepatitis B (CHB). Among HBeAg-negative CHB patients with low HBV DNA levels, HBsAg quantification may help distinguish those with active CHB from true inactive carriers with a very favourable prognosis, thus limiting the need for long-term intensive monitoring of ALT and HBV DNA levels. In patients treated with peginterferon (PEG-IFN), achievement of a decline in HBsAg during therapy appears to be an important marker for treatment outcome, and several groups have proposed stopping rules based on HBsAg thresholds. A recently described stopping rule incorporating a combination of HBsAg and HBV DNA levels can accurately identify HBeAg-negative patients, especially those with HBV genotype D, not responding to PEG-IFN. Current applications of HBsAg levels in the monitoring of patients treated with nucleo(s)tide analogues are still being evaluated. First data from these studies show that HBsAg decline, and thus subsequent clearance, is confined to those with an active immune response to HBV, such as HBeAg-positive patients with elevated ALT, or those who achieve HBeAg clearance.     

Telbivudine vs tenofovir in hepatitis B e antigen-negative chronic hepatitis B patients: OPTIMA roadmap study

AIM To make efficacy and safety comparison of telbivudineraodmap and tenofovir-roadmap in hepatitis B e antigen(HBe Ag)-negative chronic hepatitis B(CHB) patients.METHODS This was the first prospective, randomised, two-arm, open-label, non-inferiority study in HBe Ag-negative CHB patients that compared telbivudine and tenofovir administered as per roadmap concept. Patients were treated up to 24 wk and, depending on virologic response, continued the same therapy or received addon therapy up to 104 wk. Eligible patients received an additional 52 wk of treatment in the extension period(i.e., up to 156 wk). Patients who developed virologic breakthrough(VB) while on monotherapy also received add-on therapy. The primary efficacy endpoint was the rate of patients achieving hepatitis B virus(HBV) DNA 300 copies/m L at week 52. Secondary efficacy endpoints included the rates of HBV DNA 300 and 169 copies/m L, HBV DNA change from baseline, alanine aminotransferase normalisation, hepatitis B surface antigen(HBs Ag) loss, HBs Ag seroconversion, VB, and emergence of resistance at various timepoints throughout the study. Safety and estimated glomerular filtration rate(e GFR) were also analysed.RESULTS A total of 241 patients were randomised. Non-inferiority of telbivudine arm to tenofovir arm was demonstrated at week 52(± 7 d window), with over 91% of patients in each treatment arm achieving HBV DNA level 300 copies/m L. Both arms were similar in terms of key secondary efficacy variables at weeks 104 and 156. The percentage of patients achieving HBV DNA 300 copies/m L remained high and was similar in the telbivudine and tenofovir arms at both weeks 104 and 156. Over 82% of patients in both arms achieved alanine aminotransferase normalisation at week 52, and this percentage remained high at weeks 104 and 156. Telbivudine treatment progressively reduced serum HBs Ag levels from baseline while no change was reported in quantitative HBs Ag during therapy with tenofovir. Both treaments showed acceptable safety profiles. The telbivudine arm showed e GFR improvement unlike the tenofovir arm.CONCLUSION Efficacy was shown for both telbivudine-roadmap and tenofovir-roadmap regimens in HBe Ag-negative CHB patients over 156 wk. Telbivudine arm was associated with renal improvement.     

慢性乙型肝炎患者血清HBV DNA水平与HBsAg和HBeAg水平的相关性分析

目的探讨慢性乙型肝炎患者血清HBV DNA水平与HBsAg和HBeAg滴度的关系。方法在951例慢性乙型肝炎患者,采用FQ-PCR法和Abbott化学发光微粒子免疫分析技术分别测定血清HBV DNA水平及HBsAg和HBeAg滴度,分析HBV DNA水平与HBsAg和HBeAg滴度的相关性。结果在951例患者中,HBVDNA阳性率为53.83%(512/951);患者血清HBV DNA水平与HBsAg和HBeAg滴度呈正相关(rs=0.45和re=0.49,P<0.05);在HBV DNA水平≥7lg拷贝/毫升患者,血清HBsAg和HBeAg滴度高于HBV DNA为3～7lg拷贝/毫升患者,HBV DNA为3～7lg拷贝/毫升患者血清HBsAg和HBeAg滴度大于HBV DNA<3lg拷贝/毫升患者,差异均有统计学意义(P<0.05);将HBsAg分为<1000 IU/ml、1000～10000 IU/ml和≥10000 IU/ml3组,结果不同HBsAg滴度患者血清HBV DNA水平差异有统计学意义(P<0.05)。结论在血清HBV DNA≥7lg拷贝/毫升和HBsAg滴度≥10000 IU/mL患者,HBV DNA水平与HBsAg滴度呈正相关,在HBV DNA>3 lg拷贝/毫升患者,血清HBV DNA水平与HBeAg滴度呈正相关。     

Coexistence of low levels of HBsAg and high levels of anti-HBs may increase risk of hepatocellular carcinoma in chronic hepatitis B patients with high HBV load

ObjectiveThe clinical significance of coexistence of HBsAg/anti-HBs in chronic hepatitis B (CHB) patients remains controversial. This study was aimed to assess the association of this serological pattern with hepatocellular carcinoma (HCC) in patients with CHB.MethodsIn this cross-section study, 206 CHB patients with coexistence of HBsAg/anti-HBs and 206 CHB patients with HBsAg alone were included to evaluate the risk of HCC development by logistic regression analysis. In addition, a retrospective cohort of 260 patients with CHB was recruited to estimate the cumulative incidence of HCC by Kaplan–Meier analysis.ResultsThe serological pattern of coexistence of HBsAg/anti-HBs, with high levels of (“High”) HBsAg/low levels of (“Low”) anti-HBs, were considered as independent risk factors for HCC. In particular, patients with “High” HBsAg/“High” anti-HBs [odds ratio (OR), 4.295; 95% confidence interval (CI), 1.104–16.699; p = 0.035] and “Low” HBsAg/ “High” anti-HBs (OR, 3.207; 95%CI, 1.299–7.919; p = 0.012) exhibited significantly higher risk for HCC development. However, only “Low” HBsAg /“High” anti-HBs might increase risk of HCC in CHB patients with high HBV load (logrank p < 0.001) in our cohort study.ConclusionThe coexistence of “Low” HBsAg /“High” anti-HBs might increase the risk of HCC development in CHB patients with high HBV load, which reflected that the long-term interaction between immune response and virus might lead to the development of HCC. The identification of the patients with poor prognosis will help clinicians to refine the therapeutic decisions and individualize follow-up strategies.     

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.     

Quantification of hepatitis B surface antigen and E antigen: correlation between Elecsys and Architect assays

Quantification of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) and their change model during treatment are emerging as a useful tool for assessing the outcome of hepatitis B virus (HBV) infection and predicting the efficacy of antiviral therapy. The aim of this study was to compare the performance of the Elecsys and Architect assays for HBsAg and HBeAg quantification. Quantification of HBsAg and HBeAg, determined by these two assays, were assessed in 1292 sera from patients with chronic hepatitis B(CHB). HBeAg quantification in serum was performed by calibrating the results through HBeAg Paul‐Ehrlich international (PEI) reference standard. The HBV genotype was determined by direct sequencing and phylogenetic analysis. Of 1292 samples, the distribution of genotype was 514 (39.78%) genotype B, 776 (60.06%) genotype C, 2 (0.16%) genotype D. The results of HBsAg and HBeAg quantification between the Architect and Elecsys assays were significantly correlated (HBsAg: r = 0.939; HBeAg: r = 0.987), independent of HBV genotype and treatment phase. The mean differences between the two methods (the log₁₀ [Elecsys] ‐ the log₁₀ [Architect]) were 0.075 log₁₀ IU/mL and ?0.149 log₁₀PE IU/mL in quantifying HBsAg and HBeAg, respectively. This study demonstrates a high correlation between the Elecsys and the Architect assays in quantifying HBsAg and HBeAg, regardless of HBV genotype. Both the two assays can be used to monitor the HBsAg and HBeAg levels in patients with chronic hepatitis B.     

非活动性HBsAg携带者临床特征及自发性HBsAg血清学清除相关因素分析

目的了解非活动性HBsAg携带者(inactive HBsAg carriers,IHC)临床特征及自发性HBsAg血清学清除相关因素。方法纳入2009年1月至2015年12月在北京佑安医院就诊且至少随访一次的IHC 289例,所有患者均未接受任何核苷类似物和(或)干扰素抗病毒治疗。将对随访过程中是否出现自发性HBsAg血清学清除患者进行差异比较。结果289例IHC的ALT水平为(21.40±7.64)U/L,血清HBsAg、HBeAg、HBV DNA水平分别为4592.00(2262.00,6741.00)COI、0.10(0.09,0.12)COI和430.05(213.25,824.25)IU/mL。血清HBsAg与HbeAg呈正相关(r=1.86,P<0.01),与年龄呈负相关(r=-1.82,P<0.01),与HBV DNA(r=0.09,P=0.58)无明显相关性。平均随访3年,其中17例(2.60%)患者发生自发性HBsAg血清学清除,年发生率为0.87%,其血清HBsAg、HBeAg、HBV DNA水平明显低于无自发性HBsAg血清学清除者(均P<0.01),而两组之间年龄、性别、肝功能等无明显差异。结论在IHC中,血清HBsAg与HBV DNA水平无明显相关性,血清HBsAg、HBeAg、HBV DNA水平较低者更易发生自发性HBsAg血清学清除。