Long-term efficacy of plasma-derived hepatitis B vaccine among Chinese children: a 12-year follow-up study

INTRODUCTION To evaluate long-term efficacy of a plasma-derived hepatitis B vaccine and provide evidence for decision-making on the vaccine booster doses, we conducted a prevalent follow-up study to examine serologic changes in hepatitis markers and vaccine efficacy in 350 children from the original cohort of 513 children who participated in a randomized, double-blind and placebo-controlled trial on a plasma-derived hepatitis B vaccine in Longan County, Guangxi Autonomous Region, China, in 1982.     

Dilemma of HBsAg seroconversion in chronic hepatitis B infection: Dilemma of HBsAg in chronic HBV

Patients with chronic hepatitis B infection should be followed up to identify possible changes in disease status, such as HBsAg seronversion. There are little data on the outcome of such cases, and the response rate to HBV vaccine has not been discussed extensively.     

Clinical Implications of HBsAg Quantification in Patients with Chronic Hepatitis B

Quantification of serum hepatitis B surface antigen (HBsAg) helps the management of patients with chronic hepatitis B virus (HBV) infection. Median HBsAg levels differ significantly during the natural history of HBV infection, progressively declining from immune tolerance to inactive phase. The combination of an HBsAg <1000 IU/mL and HBV DNA <2000 IU/mL at a single time point accurately identifies true inactive carriers. During antiviral treatment, HBsAg levels decline more rapidly in patients under peg-interferon (Peg-IFN) than in those under nucleos(t)ide analogues (NUC), and in responders to peg-IFN compared to non responders suggesting that a response-guided therapy in both HBeAg-positive and -negative patients treated with Peg-IFN could improve to cost-effectiveness of this therapeutic approach. Given the low rates of HBsAg clearance on NUC therapy, new studies to test whether Peg-IFN and NUC combination fosters HBsAg decline in long-term responders to NUC, are being explored.     

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.     

Hepatitis B virus infection status in the PBMC of newborns of HBsAg positivemothers

AIM To study the hepatitis B virus (HBV) status in peripheral blood mononuclear cells (PBMC) and itsrelationship with serum HBV infection in newborns of hepatitis B surface antigen (HBsAg) positive mothers.METHODS Blood specimens were collected by femoral puncture from newborns of HBsAg positive motherswithin 24 hours after birth between February, 1997 and May, 1998. All sera were examined for HBV DNAand HBsAg by nested polymerase chain reaction (nPCR) and enzyme-linked immunosorbent assay (ELISA).PBMC were separated from above blood specimen of newborns. Fifty-five FBMC smear of newborns wereobtained whose sera were HBV DNA positive and 38 PBMC smear were randomly selected from newbornswhose'sera were HBV DNA negative. These Ninety-three smear of newborns' PBMC at birth were detectedfor HBV DNA by in situ polymerase chain reaction (IS PCR) and in situ hybridization (ISH) using digoxin-labelled HBV DNA probe.RESULTS Twenty-seven (49.09%) out of 55 HBV DNA positive newborns sera had HBV DNA in PBMCand 4 (10.53%) out of 38 HBV DNA negative newborns sera were detected for HBV DNA in their PBMC byISH. Sixty-two HBV DNA negative newborns PBMC by ISH were examined for HBV DNA by IS PCR. Ten(35.71%) out of 28 HBV DNA positive newborns sera had HBV DNA in their PBMC. Two (5.88%) out of 34 HBV DNA negative newborns sera were found HBV DNA in their PBMC. Total positive rates of PBMCHBV DNA (by ISH and/or IS PCR) were 67.27% (37/55) in those newborns with HBV DNA positive seraand 15.79% (6/38) in those newborns with HBV DNA negative sera.CONCLUSION HBV DNA in PBMC were found in most of newborns who had HBV DNA positive sera.But HBV DNA in PBMC also were positive in some of newborns who were negative for HBV DNA in theirsera at birth. It suggests that intrauterine HBV infection may be demonstrated only by HBV infection intheir PBMC and should be served as diagnosis index for intrauterine HBV infection. HBV infection in PBMCmay play some role in HBV intrauterine infection and its persistence, but it needs to study furthermore.     

HBV基因疫苗联合抗原蛋白免疫小鼠的研究

目的构建乙肝病毒（ＨＢＶ）基因疫苗,观察其与ＨＢＶ表面抗原蛋白（ＨＢｓＡｇ）联合免疫小鼠诱导的免疫应答．方法构建重组真核表达质粒ｐＣＲ３１Ｓ作为ＨＢＶ基因疫苗,联合应用纯ＨＢｓＡｇ蛋白免疫Ｂａｌｂ／ｃ小鼠,以单用基因疫苗ｐＣＲ３１Ｓ或纯蛋白ＨＢｓＡｇ免疫小鼠作为对照组．采用ＥＬＩＳＡ法检测免疫小鼠血清抗ＨＢｓ,另取免疫小鼠脾细胞,用３ＨＴｄＲ掺入法测定各组免疫小鼠的淋巴细胞增殖活性．结果２,４ｗｋ时联合免疫组抗ＨＢｓ效价低于纯蛋白免疫组,高于基因疫苗免疫组;６ｗｋ后基因疫苗免疫组抗ＨＢｓ效价升至最高,联合免疫组次之．３ＨＴｄＲ掺入法测定显示,各组免疫小鼠的淋巴细胞增殖反应差异不显著．结论乙肝病毒基因疫苗与表面抗原蛋白联合免疫无优势．     

慢性活动性肝炎,肝硬化患者HBV与HCV的合并感染及其意义

５８例慢性活动性肝炎，肝硬化患者中，发现乙肝表面抗原阳性４２例，抗ＨＣＶ阳性１６例，ＨＣＶ与ＨＢＶ合并感染１１例。１６例ＨＣＶ感染患者ＨＢｓＡｇ阳性率为５３．３％。ＨＣＶ与ＨＢＶ合并感染的慢性活动性肝炎患者，其谷丙转氨酶明显升高，而在肝硬化患者ＨＣＶ与ＨＶＢ合并感染对γ－ＧＴ，血清γ－球蛋白和血清白蛋白也有明显改变。     

血清HBsAg和HBeAg水平变化与慢性乙型肝炎患者抗病毒疗效预测

血清HBsAg或HBeAg定量水平的变化在慢性乙型肝炎（CHB）患者抗病毒治疗的应答中有重要预测价值,可以用于指导和调整治疗方案。本文综述了CHB患者血清HBsAg和HBeAg水平变化与HBV复制指标如血清HBV DNA和肝内HBV cccDNA间的关系,以阐明CHB患者血清HBsAg或HBeAg水平在判定抗病毒疗效方面的新认识。     

Hepatitis B Screening and Vaccination Practices in Asian American Primary Care

Background/Aims

Screening for hepatitis B virus (HBV) is recommended in populations with anticipated prevalence ≥2%. This study surveyed HBV screening and vaccination practices of Asian American primary care providers (PCPs).

Methods

Approximately 15,000 PCPs with Asian surnames in the New York, Los Angeles, San Francisco, Houston, and Chicago areas were invited to participate in a web-based survey. Asian American PCPs with ≥25% Asian patients in their practice were eligible.

Results

Of 430 (2.9%) survey respondents, 217 completed the survey. Greater than 50% followed ≥200 Asian patients. Although 95% of PCPs claimed to have screened patients for HBV, 41% estimated that ≤25% of their adult Asian patients had ever been screened, and 50% did not routinely screen all Asian patients. In a multivariable analysis, the proportion of Asian patients in the practice, provider geographic origin and the number of liver cancers diagnosed in the preceding 12 months were significantly associated with a higher likelihood of screening for HBV. Over 80% of respondents reported that ≤50% of their adult Asian patients had received the HBV vaccine.

Conclusions

Screening and vaccination for HBV in Asian American patients is inadequate. Measures to improve HBV knowledge and care by primary-care physicians are critically needed.     

Hepatitis B surface antigenaemia following vaccination with a combined vaccine against hepatitis A and B

Summary.  We report a case of transient hepatitis B surface antigenaemia (HBsAg) following vaccination with a combined vaccine against hepatitis A and B in healthy adults. This phenomenon has been observed following administration of recombinant hepatitis B (monovalent) vaccine, mainly in newborns or dialysis patients. Reports on healthy adults are much less frequent and mostly concern blood donors. The frequency of its occurrence is largely unknown but its duration does not exceed 28 days. It is not detected by all available assays. It is caused by a passive tranfer of antigen by vaccination, and not by viral replication; hence there is no risk for vaccination-induced infection. An important implication resulting from our findings is that the results of HBsAg assays should be interpreted according to the time elapsed since the last administration of a recombinant monovalent vaccine against hepatitis B or a combined vaccine against hepatitis A and B.     

高危人群微量乙肝疫苗免疫效果动态观察及有关问题探讨

采用微量乙肝疫苗（总剂量６μｇ）对ＨＢＶ高流行区的居民进行随机、对照研究，发现免疫Ｉ组（疫苗〈８℃保存）Ｔ１２抗体阳转率和保护率分别为９０．８％和８７．０％，和对照组相比，有显著性差异（Ｐ〈０．０１）；和常规剂量（总剂量９０μｇ）相比，其抗体阳转和保护率基本相同。提示高流行区同样可以用微量乙肝疫苗进行了预防。采用室温存放的乙肝疫苗作为免疫Ⅱ组进行免疫效果观察，其免疫效果和保护率与免疫Ｉ组相比，基本     

Correlation between HBsAg quantitative assay results and HBV DNA levels in chronic HBV

Background

Viral load has been used to diagnose and monitor patients who are being treated for chronic hepatitis B (CHB). The Diagnosis methods are molecular-based and expensive. Quantitation of hepatitis B surface antigen (HBsAg) by automated chemiluminescent micro-particle immunoassay has been proposed to be a surrogate marker. Quantitating HBV DNA levels molecularly is expensive; thus, a cheaper laboratory test as a surrogate diagnostic marker might simplify our management.

Objectives

We determined whether quantitative HBsAg levels correlate with HBV DNA levels in CHB.

Patients and Methods

In this cross-sectional study, all CHB patients who were referred by a gastroenterologist to undergo quantitative HBV DNA assay in a qualified laboratory in Mashhad, Iran in 2009 were enrolled, and blood samples was obtained. Patients who were positive for antibodies to HCV and HDV were excluded. HBV DNA was measured by real-time polymerase chain reaction, and serum HBsAg was quantified byelectrochemiluminescence assay (Roche Diagnostic).

Results

Of 97 patients, 70 were male (72%) and 27 were female (28%); the mean age was 39 ± 11 years. Eighty-seven percent wasHBeAg-negative. By Mann-Whitney test,HBSAg titer differed significantly between HBeAg-positive and -negative patients (P = 0.001), as did HBV DNA levels (P = 0.009). By Spearman test, there was no significant correlation between HBsAg and HBV DNA levels (P= 0.606 and r = 0.53).

Conclusions

HBeAg-negative patients have higher levels of HBsAg and lower levels of HBV DNA. By electrochemiluminescence assay,HBsAg has no significant correlation with HBV DNA levels in CHB with predominant genotype D and HBeAg negativity in Iran.     

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.     

Hepatitis B virus reactivation in hepatitis B virus surface antigen negative patients receiving immunosuppression: A hidden threat

AIM: To present the characteristics and the course of a series of anti- hepatitis B virus core antibody (HBc) antibody positive patients, who experienced hepatitis B virus (HBV) reactivation after immunosuppression. METHODS: We retrospectively evaluated in our tertiary centers the medical records of hepatitis B virus surface antigen (HBsAg) negative patients who suffered from HBV reactivation after chemotherapy or immunosuppression during a 3-year period (2009-2011). Accordingly, the clinical, laboratory and virological characteristics of 10 anti-HBc (+) anti-HBs (-)/HBsAg (-) and 4 anti-HBc (+)/antiHBs (+)/HBsAg (-) patients, who developed HBV reactivation after the initiation of chemotherapy or immunosuppressive treatment were analyzed. Quantitative determination of HBV DNA during reactivation was performed in all cases by a quantitative real time polymerase chain reaction kit (COBAS Taqman HBV Test; cut-off of detection: 6 IU/mL). RESULTS: Twelve out of 14 patients were males; median age 74.5 years. In 71.4% of them the primary diagnosis was hematologic malignancy; 78.6% had received rituximab (R) as part of the immunosuppressive regimen. The median time from last chemotherapy schedule till HBV reactivation for 10 out of 11 patients who received R was 3 (range 2-17) mo. Three patients (21.4%) deteriorated, manifesting ascites and hepatic encephalopathy and 2 (14.3%) of them died due to liver failure. CONCLUSION: HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving.     

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.     

母亲血清乙型肝炎表面抗原、e抗原滴度与新生儿接种乙型肝炎疫苗免疫失败的关系

目的 研究孕妇血清乙型肝炎表面抗原（HBsAg）、乙型肝炎e抗原（HBeAg）滴度与其新生儿接种乙型肝炎（乙肝）疫苗发生免疫失败的关系,探讨能否用孕妇血清HBsAg、HBeAg滴度代替血清HBV DNA浓度来衡量新生儿接种乙肝疫苗后发生免疫失败的危险性。方法 178例HB-sAg、HBeAg双阳性母亲的新生儿接种乙肝疫苗后,随访至24月龄,32例发生免疫失败,用斑点杂交法检测孕妇临产前血清乙型肝炎病毒（HBV）DNA浓度、用酶联免疫吸附试验（ELISA）法测定孕妇HBsAg和HBeAg浓度,研究孕妇HBsAg、HBeAg的滴度与其新生儿接种疫苗发生免疫失败的关系,并与孕妇血清HBV DNA浓度与其新生儿发生免疫的关系相比较。结果 随着母亲血清HB-sAg、HBeAg滴度的升高,其新生儿发生免疫失败的危险性升高,当孕妇血清HBsAg滴度≥1:1000、HBeAg≥1:100时,分别有26.3%、31.4%的新生儿发生乙型疫苗免疫失败,与当孕妇血清HBV DNA浓度≥125pg/ml,新生儿发生免疫失败的危险性相当。结论 孕妇血清HBsAg、HBeAg高滴度与其新生儿接种疫苗发生免疫失败有密切联系,孕妇血清HBsAg滴度≥1:1000、HBeAg滴度≥1：100能够代替血清HBV DNA浓度≥125pg/ml作为衡量孕妇的乙肝高传染性的指标来预测新生儿发生免疫失败的危险性。