Extremely high titer of hepatitis B surface antigen antibodies in a primary hepatocellular carcinoma patient: A case report

BACKGROUNDHepatocellular carcinoma (HCC) may be caused by hepatitis B virus (HBV) infection. Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen (HBsAg) level and increased anti-HBsAg antibody titer. Testing to detect HBV DNA is conducted rarely but could detect latent HBV infection persisting after acute infection and prompt administration of treatments to clear HBV and prevent subsequent HBV-induced HCC development. Here, we present an HCC case with an extremely high anti-HBsAg antibody titer and latent HBV infection.CASE SUMMARYA 57-year-old male patient with abdominal pain who was diagnosed with primary HCC presented with an extremely high level (over 2000 ng/mL) of serum alpha-fetoprotein. Abdominal B-ultrasonography and computed tomography scan results indicated focal liver lesion and mild splenomegaly. Assessments of serological markers revealed a high titer of antibodies against hepatitis B core antigen (anti-HBcAg antibodies), an extremely high titer (1000 mIU/mL) of hepatitis B surface antibodies (anti-HBsAg antibodies, anti-HBs) and absence of detectible HBsAg. Medical records indicated that the patient had reported no history of HBV vaccination, infection or hepatitis. Therefore, to rule out latent HBV infection in this patient, a serum sample was collected then tested to detect HBV DNA, yielding a positive result. Based on the aforementioned information, the final diagnosis was HCC associated with hepatitis B in a compensated stage of liver dysfunction and the patient was hospitalized for surgical treatment.CONCLUSIONA rare HCC case with high serum anti-HBsAg antibody titer and detectable HBV DNA resulted from untreated latent HBV infection.     

Quantitative analysis of hepatitis D virus RNA and hepatitis B surface antigen serum levels in chronic delta hepatitis improves treatment monitoring

BACKGROUND/AIMS: Treatment of chronic delta hepatitis is long and difficult and better monitoring is needed. METHODS: In this study, hepatitis delta virus (HDV) RNA, hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA were retrospectively quantified in 53 patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis delta. Twenty-one had received 28 courses of 3-5 MU interferon-alpha2b (IFN-alpha2b) thrice weekly for a median of 12.6 months (interquartile range [IQR]: 7.3-31.6), five had received eight courses of 100 mg lamivudine (LAM) daily for 23.6 months (IQR: 8.4-61.5) and 27 were untreated. The controls were 54 untreated, randomly selected, HBeAg-negative chronic hepatitis B patients without delta infection. Quantification of serum HDV RNA, HBsAg and HBV DNA were performed at baseline, during and at the end of treatment and end of follow up. RESULTS: Untreated patients had significantly higher median HBsAg levels than controls (5,872 vs 3,501 IU/ml; P = 0.046), but lower median HBV DNA levels (2.933 vs 6.459 log10 copies/ml; P < 0.001). Median baseline HDV RNA (6.374 log10 copies/ml) was similar in IFN-alpha2b-treated, LAM-treated and untreated patients. At the end of treatment, IFN-alpha2b significantly suppressed in paired measurements HDV RNA (P = 0.012) and HBsAg (P = 0.043), but LAM was inefficient. In IFN-alpha2b-treated patients, HDV RNA became undetectable in five patients within a median of 30 months (IQR: 8-90), followed by a slower decrease in HBsAg. CONCLUSIONS: In untreated chronic delta hepatitis, suppressed HBV replication is associated with significantly increased HBsAg serum levels. IFN-alpha2b significantly suppresses both HDV RNA and HBsAg, but LAM has no effect. Long-term IFN-alpha2b treatment (IQR: 1.5-5.0 years) appears necessary for undetectable serum HDV RNA and further treatment is required for HBsAg loss. Monitoring of HDV RNA and HBsAg serum levels in patients with chronic delta hepatitis provides insight during treatment.     

Clinical Prediction of Failure of Lamivudine Prophylaxis for Hepatitis B Virus-Infected Patients Undergoing Cytotoxic Chemotherapy for Malignancy

Although lamivudine (LAM) prophylaxis is recommended for patients infected with hepatitis B virus (HBV) undergoing chemotherapy for malignant disease, HBV reactivation sometimes occurs during or after LAM administration. The aim of this study was to determine predictors of LAM prophylactic failure in patients with malignancies. Patients with malignancies were routinely screened for serum hepatitis B surface antigen (HBsAg) from June 2002 to August 2008. All consecutive, HBsAg-positive patients received LAM prophylaxis during and after completion of chemotherapy. We assessed risk factors for virologic breakthrough and withdrawal hepatitis. Death without HBV reactivation was regarded as a competing risk event, which was adjusted by Fine and Gray''s model. A total of 110 patients were included in this study. They received LAM prophylaxis for a median of 9.2 months. Virologic breakthrough occurred in 15 patients at a median of 10.9 months from the initiation of LAM prophylaxis. Withdrawal hepatitis occurred in 15 patients at a median of 2.4 months after cessation of LAM prophylaxis. Multivariable analysis showed that high baseline HBV DNA titer (≥2,000 IU/ml) (hazard ratio [HR], 9.94; P = 0.0063) and the use of rituximab (HR, 3.19; P = 0.027) were significant predictors of virologic breakthrough and that high baseline HBV DNA titer (HR, 5.90; P = 0.007), liver cirrhosis (HR, 10.4; P = 0.002), and distant metastasis (HR, 5.14; P = 0.008) were independent risk factors for withdrawal hepatitis. Patients with high viremia, liver cirrhosis, rituximab treatment, and distant metastasis are at high risk of prophylactic failure and need antiviral agents with a greater barrier to resistance.     

Clinical cure and liver fibrosis reversal after postoperative antiviral combination therapy in hepatitis B-associated non-cirrhotic hepatocellular carcinoma: A case report

BACKGROUNDThe incidence of hepatocellular carcinoma (HCC) is high in China, and approximately 15%-20% of HCC cases occur in the absence of cirrhosis. Compared with patients with cirrhotic HCC, those with non-cirrhotic HCC have longer postoperative tumor-free survival. However, the overall survival time is not significantly increased, and the risk of postoperative recurrence remains. Strategies to improve the postoperative survival rate in these patients are currently required.CASE SUMMARYA 47-year-old man with a family history of HCC was found to have hepatitis B virus (HBV) infection 25 years ago. In 2000, he was administered lamivudine for 2 years, and entecavir (ETV 0.5 mg) was administered in 2006. In October 2016, magnetic resonance imaging revealed a tumor in the liver (5.3 cm × 5 cm × 5 cm); no intraoperative hepatic and portal vein and bile duct tumor thrombi were found; and postoperative pathological examination confirmed a grade II HCC with no nodular cirrhosis (G1S3). ETV was continued, and no significant changes were observed on imaging. After receiving pegylated interferon alfa-2b (PEG IFNα-2b) (180 μg) + ETV in February 2019, the HBsAg titer decreased significantly within 12 wk. After receiving hepatitis B vaccine (60 μg) in 12 wk, HBsAg serological conversion was realized at 48 wk. During the treatment, no obvious adverse reactions were observed, except for early alanine aminotransferase flares. The reexamination results of liver pathology were G2S1, and reversal of liver fibrosis was achieved.CONCLUSIONThe therapeutic regimen of ETV+ PEG IFNα-2b + hepatitis B vaccine for patients with HBV-associated non-cirrhotic HCC following hepatectomy can achieve an HBV clinical cure and prolong the recurrence-free survival.     

Seropositivity of hepatitis B e antigen and hepatocellular carcinoma

Chronic infection with hepatitis B virus (HBV) is an important clinical problem due to its worldwide distribution and potential of adverse sequelae including hepatocellular carcinoma (HCC). Hepatitis B e antigen (HBeAg) is a biomarker of active viral proliferation in hepatocytes and infectivity. The prevalence of HBeAg among subjects chronically infected with HBV decreases with the increase in age. Case series studies have found a lowest seroprevalence of HBeAg in HCC patients compared with patients affected with chronic hepatitis B and liver cirrhosis. Case‐control studies have shown a significantly higher seroprevalence of HBeAg in HCC cases than matched controls. A recent long‐term follow‐up study has shown a significantly elevated HCC risk for seropositives of both hepatitis B surface antigen (HBsAg) and HBeAg compared with seropositives of HBsAg only and seronegatives. The biological gradient remained in further stratification analyses by serum level of alanine transaminase and status of liver cirrhosis detected by ultrasonography. The cumulative HCC risk from age 30 to 70 years has been estimated to be 87% for those who were persistently seropositive on HBsAg and HBeAg, 12% for those with persistent seropositivity of HBsAg only, and 1% for those who were seronegative on HBsAg and HBeAg.     

Reactivation of hepatitis B virus during targeted therapies for cancer and immune-mediated disorders

ABSTRACT

Introduction: Targeted therapies have gained popularity in the treatment of several oncologic and immune-mediated diseases. Immunosuppression caused by these drugs has been associated to reactivation of hepatitis B virus (HBV) in both hepatitis B surface antigen (HBsAg) positive patients (overt infection) and HBsAg negative/anti-hepatitis B core antigen (anti-HBc) positive carriers (resolved infection), leading to premature discontinuation of therapy and potentially fatal hepatitis.

Areas covered: This review summarizes the evidence of HBV reactivation in patients with overt or resolved HBV infection undergoing targeted therapies for cancer or immune-mediated disorders, providing recommendations for the management of these patients.

Expert opinion: The risk of HBV reactivation relies on the immunosuppressive potency and duration of these therapies, the underlying disease and the virological patient’s profile. However, HBV reactivation is preventable by screening for HBV markers in all patients scheduled to receive targeted therapies, assessing the virological profile and patient’s clinical state, followed by appropriate antiviral treatment or prophylaxis in those patients at high risk of HBV reactivation. Close monitoring of HBV carriers at low risk of reactivation is warranted with the aim to start antiviral therapy as soon as HBV reactivates.     

HBsAg loss is not an ideal indicator for discontinuing treatment of HBeAg-negative chronic hepatitis B: a case report

We experienced a case of a 36-year-old married man who was found to be hepatitis B virus (HBV) positive at 23 years of age. His liver function was repeatedly abnormal in the past 13 years. In November 2007 he presented with fatigue. Laboratory tests showed serum alanine aminotransferase concentration 255.3 U/l, positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antibody, HBV DNA 3.01 × 10⁷ copies/ml; liver biopsy showed necroinflammatory scores 11 and fibrosis scores 4. After 20 weeks of treatment with Peg-IFN α-2b, laboratory tests showed HBV DNA <500 copies/ml and normal liver function. By week 52 of the treatment, HBsAg became negative. By week 92 of continuing treatment, HBsAb became weakly positive and Peg-IFN α-2b treatment was stopped. On follow-up, both HBsAg and HBsAb were negative 28 weeks after discontinuation of Peg-IFN α-2b. We then performed a second liver biopsy and histological examination revealed necroinflammtary scores 2 and fibrosis scores 2. We administered hepatitis B vaccine intramuscularly every 4 weeks combined with IFN α-1b 30 μg intramuscularly every other day. HBsAb was 244.8 IU/l at week 32 of this combined treatment. Follow-up showed that after discontinuation of the combined treatment HBsAb concentration declined rapidly but could be maintained above 100 IU/l by intermittent injections of hepatitis B vaccine. Findings from this case reveal that HBsAg loss may be not sufficient; however, HBsAg seroconversion together with maintenance of certain concentrations of HBsAb may be a better endpoint to HBV treatment.     

Long-term presence of HBV in the sera of chronic hepatitis B patients with HBsAg seroclearance

OBJECTS: The aim of this study was to elucidate the presence of serum hepatitis B virus (HBV) DNA at a prolonged time after seroclearance of hepatitis B surface antigen (HBsAg). METHODS: Seventy Japanese patients who had been observed for >5 years after HBsAg seroclearance were included in this study. Anti-HBs, anti-HBe and anti-HBc antibodies were measured 0, 5 and 10 years after HBsAg seroclearance. Serum HBV DNA was measured using nested polymerase chain reaction (PCR) at 0, 5 and 10 years after HBsAg seroclearance. The PCR detection of serum HBV DNA using the X gene and core gene primers was done. The HBV DNA was regarded as positive when PCR detection of HBV DNA using either or both the X gene and core gene primers was positive. A multivariate regression analysis was used to assess the factors contributing to the positivity of serum HBV DNA 5 years after HBsAg seroclearance: the factors examined included age, gender, histological findings, HBV genotype, aminotransferase, total protein and interferon administration. RESULTS: The titers of 200-fold diluted serum anti-HBc were 6.5 +/- 4.0 at 0 year after HBsAg seroclearance, 1.8 +/- 1.4 at 5 years and 0.9 +/- 0.7 at 10 years. The titers of 200-fold diluted serum anti-HBc decreased 5 and 10 years after HBsAg seroclearance with statistical significance. The positive rate of HBV DNA by the nested PCR was 71.4% (50/70) at 0 year after HBsAg seroclearance, 21.4% (15/70) at 5 years and 14.3% (3/21) at 10 years. However, there were no significant factors contributing to the positivity of serum HBV DNA 5 years after HBsAg seroclearance. CONCLUSION: Our results suggest that serum HBV DNA disappears with an incidence of 10-20% 5 and 10 years after HBsAg seroclearance.     

Posttransfusion hepatitis B transmitted by blood from a hepatitis B surface antigen-negative hepatitis B virus carrier

A female blood donor at our institution was implicated in three cases of clinical posttransfusion hepatitis B. She had given blood 25 times in 8 years. Twenty-seven recipients were followed up, and about one-half of those who were still living had serologic markers of hepatitis B virus (HBV) infection. The donor was repeatedly negative for hepatitis B surface antigen (HBsAg) and antibody, but she had high titers of antibody to hepatitis B core antigen. We conclude that blood from this HBsAg-negative blood donor was capable of transmitting hepatitis B.     

Immunological and Antiviral Responses After Therapeutic DNA Immunization in Chronic Hepatitis B Patients Efficiently Treated by Analogues

A substudy of a phase I/II, prospective, multicenter clinical trial was carried out to investigate the potential benefit of therapeutic vaccination on hepatitis B e antigen-negative patients with chronic hepatitis B (CHB), treated efficiently with analogues. Patients were randomized in 2 arms, one receiving a hepatitis B virus (HBV) envelope DNA vaccine, and one without vaccination. At baseline, HBV-specific interferon (IFN)-γ–producing T cells were detected in both groups after in vitro expansion of peripheral blood mononuclear cells. Vaccine-specific responses remained stable in the vaccine group, whereas in the control group the percentage of patients with HBV-specific IFN-γ–producing T cells decreased over time. The vaccine-specific cytokine-producing T cells were mostly polyfunctional CD4⁺ T cells, and the proportion of triple cytokine-producer T cells was boosted after DNA injections. However, these T-cell responses did not impact on HBV reactivation after stopping analogue treatment. Importantly, before cessation of treatment serum hepatitis B surface antigen (HBsAg) titers were significantly associated with DNA or HBsAg clearance. Therapeutic vaccination in CHB patients with persistent suppression of HBV replication led to the persistence of T-cell responses, but further improvements should be searched for to control infection after treatment discontinuation.     

Thyroid dysfunction is associated with the loss of hepatitis B surface antigen in patients with chronic hepatitis B undergoing treatment with α-interferon

ObjectiveTo investigate the influence of thyroid dysfunction on the antiviral efficacy of α-interferon in adult patients with chronic hepatitis B (CHB).MethodsWe performed a retrospective study of 342 patients with CHB who underwent interferon treatment for >12 weeks. Patients with thyroid dysfunction before or during treatment were defined as the thyroid dysfunction group (n = 141) and those with normal thyroid function were defined as the normal thyroid function group (n = 201). The prevalences of hepatitis B virus (HBV) DNA undetectability, low hepatitis B surface antigen (HBsAg) titre (<250 IU/mL), HBsAg loss, and hepatitis B envelope antigen loss were compared.ResultsDuring interferon treatment, 69 of 270 (25.6%) participants with normal thyroid function at baseline developed thyroid dysfunction, whereas 11 of 72 (15.3%) with thyroid dysfunction at baseline regained normal thyroid function. The thyroid dysfunction group had significantly higher prevalences of low HBsAg titre (29.8% vs. 18.9%) and HBV DNA undetectability (66.0% vs. 40.3%). Multivariate logistic regression analysis showed that thyroid dysfunction was associated with HBsAg loss (odds ratio 4.945, 95% confidence interval 1.325–18.462).ConclusionsThese results suggest that thyroid dysfunction is not an absolute contraindication, but is associated with HBsAg loss, in patients with CHB undergoing α-interferon treatment.     

Effect of Pegylated Interferon Plus Tenofovir Combination on Higher Hepatitis B Surface Antigen Loss in Treatment-naive Patients With Hepatitis B e Antigen -positive Chronic Hepatitis B: A Real-world Experience

PurposeThe loss of serum hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) is considered an ideal clinical outcome but rarely achieved with current standard of care. We evaluated the effectiveness in inducing HBsAg seroclearance in a real-world clinical cohort of Chinese patients with CHB treated with a combination of pegylated interferon (Peg-IFN) with tenofovir disoproxil fumarate (TDF) or monotherapy with each agent.MethodsA total of 330 patients with CHB were assigned to receive Peg-IFN plus TDF for 48 weeks (Peg-IFN plus TDF group), Peg-IFN alone for 48 weeks (Peg-IFN group), or TDF alone for 144 weeks (TDF group). The primary end point was the percentages of patients who achieved HBsAg seroclearance at week 72. Differences from the baseline characteristics and treatment data were compared using the χ² test for categorical variables or 1-way ANOVA for continuous variables. A Kaplan–Meier test was performed to compare the HBsAg loss among the 3 groups. Discrimination of responders versus nonresponders was quantified using AUC curves. Optimal cut-offs were selected based on Youden's J statistic defined as J = sensitivity + specificity-1.FindingsAt week 72, the Kaplan–Meier cumulative HBsAg loss was 11.5% in the Peg-IFN plus TDF group, 5.7% in the Peg-IFN group, and 0% in the TDF group. The percentage of patients with HBsAg loss was comparable in the Peg-IFN plus TDF and Peg-IFN groups (P = 0.143), but both were significantly higher than that in the TDF group (P = 0.000 and P = 0.010). In addition, a significantly higher percentage of patients in the combination group and Peg-IFN group had serum HBsAg of <100 IU/mL compared with the TDF group (32.7% vs 23.6% vs 9.2%; P < 0.001) but no significant differences in the percentages of patients with HBsAg <1000 IU/mL, the undetectable serum HBV DNA and hepatitis B e antigen seroconversion. Our model predicted serum HBsAg loss at week 72 (AUC = 0.846) if the HBsAg level was reduced by > 1.5 log₁₀ IU/mL from baseline at treatment week 24, an optimal timepoint for prediction of HBsAg loss in this cohort.ImplicationsA 48-week course of Peg-IFN and TDF combination therapy led to profound reduction in serum HBsAg level, resulting in a significantly higher rate of HBsAg loss compared with TDF monotherapy. Patients with steep HBsAg decline >1.5 log₁₀ IU/mL at week 24 well signaled a higher probability of achieving HBsAg loss at week 72.     

Seropositivity of hepatitis B e antigen and hepatocellular carcinoma

Chronic infection with hepatitis B virus (HBV) is an important clinical problem due to its worldwide distribution and potential of adverse sequelae including hepatocellular carcinoma (HCC). Hepatitis B e antigen (HBeAg) is a biomarker of active viral proliferation in hepatocytes and infectivity. The prevalence of HBeAg among subjects chronically infected with HBV decreases with the increase in age. Case series studies have found a lowest seroprevalence of HBeAg in HCC patients compared with patients affected with chronic hepatitis B and liver cirrhosis. Case-control studies have shown a significantly higher seroprevalence of HBeAg in HCC cases than matched controls. A recent long-term follow-up study has shown a significantly elevated HCC risk for seropositives of both hepatitis B surface antigen (HBsAg) and HBeAg compared with seropositives of HBsAg only and seronegatives. The biological gradient remained in further stratification analyses by serum level of alanine transaminase and status of liver cirrhosis detected by ultrasonography. The cumulative HCC risk from age 30 to 70 years has been estimated to be 87% for those who were persistently seropositive on HBsAg and HBeAg, 12% for those with persistent seropositivity of HBsAg only, and 1% for those who were seronegative on HBsAg and HBeAg.     

浙江省湖州市自然人群乙型病毒性肝炎的流行特征

目的 了解浙江省湖州市自然人群乙型病毒性肝炎(乙肝)病毒(HBV)感染情况与流行病学特征.方法 在湖州市按农村山区、农村平原水乡、城镇,随机抽取1666名健康人为研究对象,用酶联免疫吸附试验检测血清乙肝病毒表面抗原、乙肝病毒表面抗体、乙肝病毒核心抗体、乙肝病毒e抗原、乙肝病毒e抗体.结果 湖州市自然人群HBV标化流行率为36.47%,乙肝流行率＜10岁组儿童最低,为4.93%;HBsAg携带率为4.14%,10岁以下携带率为0;低于全国和全省人群乙肝流行率.结论 湖州市乙肝流行率已从高流行区进入中流行区,乙肝疫苗接种效果明显.     

乙肝肝硬化患者血清HBsAg与HBVDNA比值在不同病程差异及疗效价值研究

目的 研究分析乙型肝炎表面抗原(HbsAg)与乙型肝炎病毒(HBV)DNA比值在不同严重程度慢性乙型肝炎(CHB)病毒感染患者中差异及其对疗效的预测价值。方法 选取该院33例轻中度CHB者为A组、41例重度CHB者为B组和38例乙型肝炎肝硬化者为C组。对各组患者总胆红素(TBIL)和谷氨酸氨基转移酶(ALT)等指标的水平进行检测,并对其HBsAg,HBV DNA进行检测。结果 ①C组HBsAg,HBV DNA较A,B组均显著降低(P<0.05),而三组间HBsAg与HBV DNA比值的比较,差异无统计学意义(P>0.05); ②A组与B组HBsAg,HBV DNA,HBsAg与HBV DNA比值的比较,差异均无统计学意义(P>0.05)。③完全应答组治疗后3个月HBsAg,HBV DNA较治疗前均显著降低,差异有统计学意义(P<0.05),HBsAg与HBV DNA比值较治疗前显著升高(P<0.05)。④部分应答组、无应答组治疗后3个月HBsAg与治疗前比较,均无统计学意义(P>0.05),而HBV DNA较治疗前均显著降低(P<0.05)。⑤HBsAg与HBV DNA比值较治疗前均显著升高(P<0.05)。⑥相比HBsAg(0.54),HBV DNA(0.42),HBsAg与HBV DNA比值预测临床疗效的ROC曲线下面积(0.67)显著升高。结论 乙型肝炎肝硬化患者HBsAg与HBV DNA比值明显高于CHB患者,并且该比值对疗效的预测价值明显高于HBsAg,HBV DNA。     

Performance of hepatitis B assays on the Bayer ADVIA Centaur Immunoassay System

Bayer HealthCare LLC, Diagnostics Division, has developed several new assays on the ADVIA Centaur immunoassay system for the detection of markers of hepatitis B virus infection in human serum and plasma. This panel includes assays for: hepatitis B surface antigen (HBsAg), a confirmatory test method for HBsAg, antibodies to hepatitis B surface antigen (anti-HBs), IgM and IgG antibodies to hepatitis B core antigen (anti-HBc Total) and IgM antibodies to hepatitis B core antigen (anti-HBc IgM). These assays employ magnetic particle separation technology with direct chemiluminescence for optimal assay performance. All of the assays are fully automated, require sample volumes ranging from 15 microl to 100 microl (with the exception of the ADVIA Centaur HBsAg Confirmatory Assay, which requires 2 x 100 microl), and have throughputs of up to 240 tests per hour. The five ADVIA Centaur HBV assays were tested in extensive performance evaluations conducted at two sites in Europe. The performance evaluations, which included samples from HBV-infected individuals, blood donors, hospitalized/clinical patients, and HBV vaccinees (for Anti-HBs evaluation), generated performance data in support of obtaining the Communautés Européennes (CE) mark for European market distribution. The HBV performance evaluations resulted in an overall diagnostic specificity > 99%, i.e. 99.94% for the ADVIA Centaur HBsAg Assay, 100% for the ADVIA Centaur Anti-HBs Assay, 100% for the ADVIA Centaur HBc IgM Assay and 99.94% for the ADVIA Centaur HBc Total Assay. All of the ADVIA Centaur assays showed a very good diagnostic sensitivity on these populations with 100% for the ADVIA Centaur HBsAg Assay, 99.0% for the ADVIA Centaur Anti-HBs Assay, 98.53% for the ADVIA Centaur HBc IgM Assay and 100% for the ADVIA Centaur HBc Total Assay. The ADVIA Centaur HBsAg Confirmatory Test confirmed 100% of the positive HBsAg samples. Testing of interfering substances and potential cross-reacting samples for all ADVIA Centaur HBV assays resulted in no change in interpretation of the results. Assay performance was further evaluated using HBV seroconversion panels with comparable or better results when compared to the comparison assays. The performance evaluation data demonstrate that the ADVIA Centaur HBV assays are specific and sensitive automated immunoassays for detection of antigens and antibodies to hepatitis B virus with performance that is comparable to those of currently marketed assays. Additionally, these assays have the advantage of being available on the ADVIA Centaur immunoassay system, which provides for the flexibility of high throughput and full automation.     

Risk factors for de novo hepatitis B during solid cancer treatment

BACKGROUNDReactivation of hepatitis B virus (HBV) during anticancer treatment is a critical issue. When treating patients with solid tumors, it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive patients, so-called de novo hepatitis B patients. The risk of de novo hepatitis B may vary based on different background factors.AIMTo determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment.METHODSThis retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies (HBsAbs). The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements. Patient characteristics and disease and treatment information were investigated. HBV DNA measurements were performed using TaqMan polymerase chain reaction (PCR). To identify the risk factors associated with HBV DNA expression, the age, sex, original disease, pathology, treatment method, presence or absence of hepatitis C virus (HCV), and HBsAb and/or HBcAb titers of all subjects were investigated. In patients with HBV DNA, the time of appearance, presence of HBsAgs and HBsAbs at the time of appearance, and course of the subsequent fluctuations in virus levels were also investigated.RESULTSAmong the 1040 patients, 938 were HBcAb positive, and 102 were HBcAb negative and HBsAb positive. HBV DNA expression was observed before the onset of treatment in nine patients (0.9%) and after treatment in 35 patients (3.7%), all of whom were HBcAb positive. The HBV reactivation group showed significantly higher median HBcAb values [9.00 (8.12-9.89) vs 7.22 (7.02-7.43), P = 0.0001] and significantly lower HBsAb values (14 vs 46, P = 0.0342) than the group without reactivation. Notably, the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption (79.0% vs 58.7%, P = 0.0051). A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation (multivariate analysis, P = 0.0002 and P = 0.0095). The group without HBsAbs tended to have a shorter time to reactivation (day 43 vs day 193), and the frequency of reactivation within 6 mo was significantly higher in this group (P = 0.0459) than in the other group.CONCLUSIONA high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.     

In vitro antiviral activity of three enantiomeric sesquiterpene lactones from Senecio species against hepatitis B virus

Three enantiomeric sesquiterpene lactones were isolated under the bioguidance of the suppression of hepatitis B virus (HBV) surface antigen (HBsAg) from Senecio species, a widely distributed Chinese medicinal herb traditionally used for the treatment of hepatitis B, dermatosis and inflammation. The anti-HBV activity of the purified compounds was measured; all of them showed suppressive activity on the expression of HBsAg and HBV e antigen (HBeAg) in the HepG2.2.15 cell line. Real-time quantitative PCR analysis showed that the studied compounds decreased the number of infectious virions released, but did not inhibit the intracellular HBV DNA. The results suggest that enantiomeric sesquiterpene lactones may possess the potential to work synergistically with other antiviral compounds for the treatment of HBV infection.     

A decline in hepatitis B virus surface antigen (hbsag) predicts clearance, but does not correlate with quantitative hbeag or HBV DNA levels

BACKGROUND: The elimination of hepatitis B virus surface antigen (HBsAg) is the final goal of hepatitis B treatment, but is rarely achieved. As quantitative assays for HBsAg recently became available, we have investigated whether quantitative HBsAg measurements can substitute for hepatitis B virus (HBV) DNA quantification in treatment monitoring. METHODS: Within this study, 23 liver transplant patients and 18 heart transplant recipients were retrospectively analysed. Patients had been treated with famciclovir and/or lamivudine, in addition some had also received adefovir in cases of lamivudine resistance. Quantitative HBsAg and hepatitis B virus e antigen (HBeAg) levels were determined with the Architect assay. HBV DNA levels were determined with different assays available at given time points. RESULTS: We did not find a significant correlation between either HBsAg or HBeAg and HBV DNA levels - both in treated and untreated patients. More importantly, there was no significant concordance between an increase or decrease of HBsAg or HBeAg with HBV DNA. However, the curve and decline of quantitative HBsAg enabled prediction of eventual viral clearance. Eight patients showed a 2 log10 drop of HBsAg levels and eight patients demonstrated a reduction of HBsAg levels below 100 IU/ml; five patients fulfilled both criteria. Three of those five cleared HBsAg and became positive for antibodies against HBsAg. CONCLUSIONS: Quantitative HBsAg and HBeAg cannot substitute for HBV DNA quantification during the assessment of antiviral therapy; however, the decline of HBsAg does predict eventual HBsAg clearance. A 2 log10 drop to below 100 IU/ml is associated with a high likelihood of HBsAg clearance.     

乙型肝炎病毒表面抗原阴性271例隐匿性感染的研究

目的了解在乙型肝炎表面抗原（HBsAg）阴性人群中隐匿性感染情况。方法采用实时荧光定量聚合酶链反应检测271例重庆黔江区HBsAg阴性住院患者血清中HBV-DNA含量。结果271例HBsAg阴性人群血清HBV—DNA阳性率为10．7％，HBV-DNA含量均低于10^3 copy／mL。HBV—DNA检出率与性别、年龄无关。在HBV-DNA阳性人群中抗-HBc抗体出现率较高，抗-HBs阳性或乙型肝炎病毒标志物全阴性也可检出HBV-DNA。结论血清HBsAg阴性者存在一定比例的隐匿性感染，对不明原因的肝损害、输血、器官移植等应结合灵敏度高的HBV-DNA检测结果再作判断。