Incidence and prediction of HBsAg seroclearance in a prospective multi-ethnic HBeAg-negative chronic hepatitis B cohort.

BACKGROUND AND AIMS: Achieving HBsAg loss is an important landmark in the natural history of chronic hepatitis B (CHB). A more personalized approach to prediction of HBsAg loss is relevant in counseling patients. This study sought to develop and validate a prediction model for HBsAg loss based on quantitative HBsAg levels (qHBsAg) and other baseline characteristics. METHODS: The Hepatitis B Research Network (HBRN) is a prospective cohort including 1240 untreated HBeAg-negative patients (1150 adults, 90 children) with median follow-up of 5.5 years. Incidence rates of HBsAg loss and hepatitis B surface antibody (anti-HBs) acquisition were determined, and a predictor score of HBsAg loss using readily available variables was developed and externally validated. RESULTS: Crude incidence rates of HBsAg loss and anti-HBs acquisition were 1.6 and 1.1 per 100 person-years (PY); 67 achieved sustained HBsAg loss for an incidence rate of 1.2 per 100 PY. Increased HBsAg loss was significantly associated with older age, non-Asian race, HBV phenotype (inactive CHB vs. others), HBV genotype A, lower HBV-DNA levels, and lower and greater change in qHBsAg. The HBRN-SQuARe (sex,∆quantHBsAg, age, race) score predicted HBsAg loss over time with area under the receiver operating characteristic curve (AUROC) (95% CIs) at 1 and 3 years of 0.99 (95% CI: 0.987-1.00) and 0.95 (95% CI 0.91-1.00), respectively. In validation in another cohort of 1253 HBeAg-negative patients with median follow-up of 3.1 years, HBRN SQuARe predicted HBsAg loss at 1 and 3 years with AUROC values of 0.99 (0.98-1.00) and 0.88 (0.77-0.99), respectively. CONCLUSION: HBsAg loss in predominantly untreated patients with HBeAg-negative CHB can be accurately predicted over a 3-year horizon using a simple validated score (HBRN SQuARe). This prognostication tool can be used to support patient care and counseling.

EVALUATION OF SOME BIOCHEMICAL MARKERS AND THE ANTIBODY RESPONSE TO HEPATITIS B VACCINE IN HEMODIALYSIS PATIENTS.

OBJECTIVE: The aim: The goal of this study was to assess the immune response to the HB vaccine (the level of anti-HBs titer), as well as the prevalence of serum creatinine, urea, CRP, and serum albumin levels, and the relationship between these and immune response to the vaccine. PATIENTS AND METHODS: Materials and methods: 127 patients with chronic renal disease on hemodialysis (HD) were compared to 40 healthy people in Iraqi dialysis center, Baghdad. Antibodies to the hepatitis B core antigen (anti-HBc) were detected using the ARCHITECT SYSTEM and the Anti-HBs titer, HBs Ag, Anti-HCV determined by ELISA. RESULTS: Results: When compared to the poor and non-responder groups, the mean value of anti-HBs titer increased considerably in the good responder group. The good responder and control groups, on the other hand, showed no significant changes. The anti-HBs titer was found to have the strongest negative correlation with serum creatinine, blood urea, and C-reactive protein levels. There was a considerable positive connection between anti-HBs titer and albumin levels. CONCLUSION: Conclusions: The responses of HD patients to the HB vaccine revealed the significant negative relation between serum creatinine, blood urea levels, and CRP, as well as a significant positive correlation between serum albumin.

Ubiquitous expression of HBsAg from integrated HBV DNA in patients with low viral load.

BACKGROUND & AIMS: Loss of serum HBsAg is a hallmark of spontaneous and therapy induced resolution of HBV infection, since it generally reflects a profound decrease in viral replication. However, integrated HBV DNA can contribute to HBsAg expression independent of viral replication. The relative contributions of these sources of HBsAg are not well understood. Specifically, it is not known whether actively transcribed HBV integration could spread throughout the entire liver. METHODS: The relative distribution of HBsAg and HBV RNA in liver biopsy tissue from HBeAg-negative (HBe-) patients was analyzed by immunohistochemistry and in situ hybridization (ISH), respectively. Frozen biopsy tissue was used for molecular analysis of intrahepatic viral RNA, virus-host chimeric transcripts and viral DNA. RESULTS: Immunohistochemistry and ISH analysis revealed HBsAg and HBV RNA positivity in virtually all hepatocytes in the liver of some HBe- patients despite very low viremia. Reverse transcription quantitative PCR and RNA-sequencing analysis confirmed high expression levels of HBV envelope-encoding RNAs. However, the amount of viral transcriptional template (covalently closed circular (ccc)DNA) was too low to support this ubiquitous HBV RNA expression. In contrast, levels of total cellular HBV DNA were consistent with ubiquitous HBV integration. Finally, RNA-sequencing revealed the presence of many HBV-host chimeric transcripts with the potential for HBsAg expression. CONCLUSIONS: Transcriptionally active HBV integration can extend to the entire liver in some HBe- patients. This can lead to ubiquitous HBsAg expression independent of HBV replication. In such patients, HBsAg is probably not a clinically useful surrogate marker for viral resolution or functional cure. LAY SUMMARY: Loss of serum hepatitis B surface antigen (HBsAg) indicates resolution of HBV infection. However, integrated HBV DNA can contribute to HBsAg production independently of viral replication. We investigated the extent of HBsAg-producing viral integration in the livers of patients with low serum viral loads. Our findings suggest that transcriptionally active HBV integration can extend to the entire liver in some patients, questioning the clinical utility of HBsAg as a surrogate marker for viral replication.

Clinical efficacy of a novel, high-sensitivity HBcrAg assay in the management of chronic hepatitis B and HBV reactivation.

BACKGROUND & AIMS: A fully automated, novel high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developed. We demonstrate the clinical utility of iTACT-HBcrAg for monitoring chronic hepatitis B (CHB) and for the early detection of HBV reactivation. METHODS: After fundamental assessments, the clinical performance of iTACT-HBcrAg was compared with other HBV markers. i) Serial sera, available from 161 HBeAg-negative patients with CHB and persistently undetectable HBV DNA, were measured by iTACT-HBcrAg and a conventional HBcrAg assay (G-HBcrAg). ii) Serial sera from 13 HBV-reactivated patients were measured by iTACT-HBcrAg and an ultra-high-sensitivity HBsAg immune complex transfer-chemiluminescent enzyme immunoassay (lower limit of detection; 0.0005 IU/ml, ICT-CLEIA) to compare HBV DNA detection. iii) To elucidate the various HBcrAg components detected by iTACT-HBcrAg, OptiPrep density gradient centrifugation analysis was performed on sera obtained before and after HBV reactivation. RESULTS: The analytical performance of iTACT-HBcrAg was satisfactory. The sensitivity of iTACT-HBcrAg (2.1 Log U/ml) was approximately 10-fold greater than that of G-HBcrAg (2.8 Log U/ml). i) HBcrAg was detectable in the sera of 97.5% (157/161) of patients with CHB by iTACT-HBcrAg, of whom 75.2% (121/161) had ≥2.8 Log U/ml HBcrAg and 22.4% (36/161) had 2.1-2.8 Log U/ml HBcrAg, which was undetectable by G-HBcrAg. ii) 9 and 2 of 13 HBV-reactivated patients were HBcrAg-positive by iTACT-HBcrAg before and at HBV DNA positivity, respectively; 7 and 4 were HBcrAg-positive by iTACT-HBcrAg before and at HBsAg-positivity by ICT-CLEIA, respectively. iii) The HBcrAg detected by iTACT-HBcrAg before HBV reactivation was contained in empty particles (22 KDa precore protein). CONCLUSIONS: iTACT-HBcrAg could be used to better monitor responses to anti-HBV treatments in HBeAg-negative patients and for the early detection of HBV reactivation. LAY SUMMARY: A fully automated, novel high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developed. iTACT-HBcrAg can be used to monitor HBeAg-negative patients with chronic hepatitis B, as well as for the early detection of HBV reactivation. iTACT-HBcrAg could be used as a general marker of disease progression and treatment response.

Liver transplantation using hepatitis B core positive grafts with antiviral monotherapy prophylaxis.

BACKGROUND & AIMS: The impact of hepatitis B core antibody (anti-HBc) positive liver grafts on survival and the risk of de novo hepatitis B virus (HBV) infection after liver transplantation (LT) remain controversial. Therefore, we aimed to analyze this risk and the associated outcomes in a large cohort of patients. METHODS: This was a retrospective study that included all adults who underwent LT at Queen Mary Hospital, Hong Kong, between 2000 and 2015. Data were retrieved from a prospectively collected database. Antiviral monotherapy prophylaxis was given for patients receiving grafts from anti-HBc positive donors. RESULTS: A total of 964 LTs were performed during the study period, with 416 (43.2%) anti-HBc positive and 548 (56.8%) anti-HBc negative donors. The median follow-up time was 7.8 years. Perioperative outcomes (hospital mortality, complications, primary nonfunction and delayed graft function) were similar between the 2 groups. The 1-, 5- and 10-year graft survival rates were comparable in anti-HBc positive (93.3%, 85.3% and 76.8%) and anti-HBc negative groups (92.5%, 82.9% and 78.4%, p = 0.944). The 1-, 5- and 10-year patient survival rates in anti-HBc positive group were 94.2%, 87% and 79% and were similar to the anti-HBc negative group (93.5%, 84% and 79.7%, p = 0.712). One-hundred and eight HBsAg negative recipients received anti-HBc positive grafts, of whom 64 received lamivudine and 44 entecavir monotherapy prophylaxis. The risk of de novo HBV was 3/108 (2.8%) and all occurred in the lamivudine era. There were 659 HBsAg-positive patients and 308 (46.7%) received anti-HBc positive grafts. The risk of HBV recurrence was similar between the 2 groups. Donor anti-HBc status did not impact on long-term patient and graft survival, or the risk of hepatocellular carcinoma recurrence after LT. CONCLUSIONS: De novo HBV was exceedingly rare especially with entecavir prophylaxis. Anti-HBc positive grafts did not impact on perioperative and long-term outcomes after transplant. LAY SUMMARY: The risk of de novo hepatitis B infection after liver transplantation was rare when using hepatitis B core positive liver grafts with entecavir monotherapy prophylaxis. Hepatitis B core antibody status did not impact on perioperative and long-term outcomes after liver transplantation. This provides support for the clinical use of hepatitis B core positive liver grafts when required.

Monitoring and Treatment of Patients Undergoing Immunotherapy With Anti-CD20 Who are Exposed to HBV.

Reactivation of hepatitis B virus (HBV) is a potentially fatal complication of immunosuppressive therapy, and can occur in individuals who are hepatitis B surface antigen (HBsAg) negative but positive for hepatitis B core antibody (anti-HBc). While anti-HBc positivity indicates prior HBV exposure, it may also reflect clearance of HBsAg, but with viral persistence at low intrahepatic replicative and transcriptional levels.1 HBV reactivation can still occur during intense immunosuppression, including B cell-depleting therapy with anti-CD20 antibodies2 and hematopoietic stem cell transplantation.3 While prevention via antiviral prophylaxis is recommended, it remains uncertain, from a global perspective, if this is an ideal and cost-effective strategy. An alternative is regular HBV DNA monitoring.4 However, this approach is problematic in resource-constrained regions, where the logistics of sample collection, transportation, and molecular analysis in dedicated facilities poses challenges.5 We aimed to evaluate the effectiveness of simple monitoring strategies using routine liver biochemistry and serum HBsAg in preventing HBV-related complications during anti-CD20 therapy.

Late hepatitis B reactivation following direct-acting antiviral-based treatment of recurrent hepatitis C in an anti-HBc-positive liver transplant recipient.

Direct-acting antivirals (DAAs) have changed the landscape of hepatitis C virus (HCV) treatment, but chronic hepatitis C (CHC) remains a leading indication for liver transplantation (LT). Hepatitis B virus (HBV) reactivation has been reported in HBV-HCV-coinfected patients treated with DAAs. We report on a case of late HBV reactivation after DAA-based treatment of recurrent hepatitis C in an antibody against hepatitis B core antigen (anti-HBc)-positive LT recipient. (Hepatology 2018;67:791-793).

Utility of oral fluid samples for hepatitis B antibody detection in real life conditions.

BACKGROUND: Hepatitis B virus (HBV) testing in oral fluid samples may provide advantages in diagnosis, screening or prevalence studies, especially among individuals with venous access difficulties. This study aims to optimize one commercially available assay for detecting total anti-HBc marker in oral fluid samples and to evaluate its utility under real life conditions in different settings for the purposes of prevalence and diagnostic studies. METHODS: Oral fluid was collected using a Salivette device and some parameters were initially evaluated: type of elution buffer and sample volume. Thereafter, the utility of oral fluid samples for detection of anti-HBc was evaluated in real life conditions in which, 1296 individuals gave serum and oral fluid samples. All serum samples were submitted to commercial EIAs to detect total anti-HBc, according to the manufacturer's instructions and oral fluid samples according to previous optimization. RESULTS: In optimization evaluation, PBS/BSA 0.5% and 100 µL of oral fluid (volume was two-fold increased compared to serum in EIA) were chosen as transport buffer and sample volume. In the field study, anti-HBc was detected in 211 out of 1296 serum samples giving overall oral fluid sensitivity of 52.6% and specificity of 96%. Concordance was higher in ambulatory setting (67.7) compared to general population (31.8). Mean ± standard deviation values of optical density/cutoff (OD/CO) in serum samples were higher in false-negative oral fluid samples than those seen in true positive samples. Sensitivity was higher in those presenting active infection compared to anti-HBc isolate and past infection. Sensitivity also increased in the ambulatory group when HCV individuals were excluded. CONCLUSIONS: It was possible to optimize a commercial EIA for detecting anti-HBc in oral fluid samples and where the highest concordance was found in ambulatory settings and among individuals with active infection.

Determination of Hepatitis B Immunoglobulin Infusion Interval Using Pharmacokinetic Half-life Simulation for Posttransplant Hepatitis B Prophylaxis.

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. This study established an individualized HBV prophylaxis protocol, through optimization of hepatitis B immunoglobulin (HBIG) administration, with application of simulative half-life (SHL). METHODS: This study involved five parts: Part 1 developed the SHL estimation method with 20 patients; Parts 2 and 3 assessed the SHL variability and developed a simulation model to apply SHL in 100 patients; Part 4 validated the simulation model in 114 patients, and Part 5 was a cross-sectional study on the current status of HBIG infusion intervals in 660 patients. RESULTS: In Part 1, infusion of 10,000 IU HBIG induced add-on rise hepatitis B surface antibody (anti-HBs) titer of 5,252.5 ± 873.7 IU/L, which was 4.4% lower than actual measurement. Mean SHL of 20.0 ± 3.7 days was 2.2% longer than actual measurement. In Part 2, the medians of the intra- and inter-individual coefficient of variation in SHL were 13.5% and 18.5%, respectively. Pretransplant HBV DNA load and posttransplant antiviral therapy did not affect SHL. In Part 3, a simulation model was developed to determine the interval of HBIG infusion, by using SHL. In Part 4, all 114 patients were successfully managed with regular HBIG infusion intervals of ≥ 8 weeks, and the interval was prolonged to ≥ 12 weeks in 89.4%, with a target trough anti-HBs titer ≥ 200 IU/L. In Part 5, 47.4% of our patients received HBIG excessively, at a target trough titer of 500 IU/L. CONCLUSION: SHL estimation using only clinically available parameters seems to be reliably accurate when compared with actual measurements. We believe that SHL estimation is helpful to establish a personalized HBV prophylaxis protocol for optimizing HBIG administration.

Evaluation of occult hepatitis B infection in tissue donors: a multicenter analysis in Spain.

Traditionally, when antibody to the Hepatitis B core antigen (anti-HBc) and antibody to the Hepatitis B surface antigen (anti-HBs) are positive, the donor is considered suitable. However, the literature contains cases with this profile and circulating hepatitis B virus DNA. The aim of the study is to analyze the incidence of occult hepatitis B virus infection (OBI). Retrospective data were evaluated for deceased tissue donors in ten Tissue Establishments (Spain) during 2017. The data included demographic data and the serological markers for hepatitis B that each tissue establishment performed. A total number of 1933 tissue donors were evaluated. A total of 180 donors were excluded: 6 (0.3%) with Hepatitis B surface antigen (HBs positive), and 174 in which DNA testing was not performed. Anti-HBc was positive in 175 donors (10%), in which anti-HBs was negative in 30 (17.1%) and positive in 145 (82.9%). In total, 27 donors with DNA positive (1.5%) were found, of which 3 of 117 donors (1.7%) showed anti-HBc negative and anti-HBs positive (> 10 IU/ml), 4 of 30 donors (13.3%) showed anti-HBc positive and anti-HBs negative and 20 of 145 donors (13.8%) showed both anti-HBc and anti-HBs positive. The highest probability of finding DNA occurs when anti-HBc is positive, regardless of the presence of anti-HBs. In our study, the probability of OBI was 1.5%. The classic concept that when anti-HBc and anti-HBs are positive (even with a titer of over 100 IU/ml) the donor can be accepted should, therefore, be reconsidered, and DNA testing should be mandatory.

Patients with core antibody positive and surface antigen negative Hepatitis B (anti-HBc+, HBsAg-) on anti-TNF therapy have a low rate of reactivation.

Anti-TNF agents are widely used to treat immune-mediated disorders. Reactivation of Hepatitis B virus (HBV) is associated with immunosuppressive agents and biologics such as anti-TNF. There are limited data and differing guidelines for patients with negative hepatitis B surface antigen (HBsAg-) but positive antibody to hepatitis B core antigen (anti-HBc+) on anti-TNF with regards to outcomes and need for anti-viral prophylaxis. We examined the prevalence of HBV reactivation in a single-center retrospective cohort study of 120 HBsAg-, anti-HBc+ patients on anti-TNF, totaling 346.6 patient years. One patient (0.8%) who had a detectable VL (<20 IU) prior to starting anti-TNF had reactivation of HBV with sero-conversion to positive HBsAg. Three patients (2.5%) had undetectable HBV VL prior to anti-TNF and developed detectable VL while on anti-TNF. In conclusion, there was a low rate of HBV reactivation or development of detectable HBV DNA in HBsAg-, anti-HBc+ patients on anti-TNF.

Determination of hepatitis B, C and D prevalence among urban and Amerindian populations from the Eastern Brazilian Amazon: a cross sectional study.

BACKGROUND: This study was conducted to determine the prevalence of HBV, HCV, and HDV in urban populations and Amerindians living in the state of Tocantins (Eastern Amazon). METHODS: A total of 948 individuals were recruited in Tocantinopolis city (Tocantins state) of whom 603 were Amerindians (from 6 tribes) and 345 were non-Amerindians (6 urban areas of Tocantinópolis city). Anti-HCV, HBsAg, anti-HBc, anti-HBs, anti-HBc IgM, anti-HBe, HBeAg, and anti-delta antibodies were determined using enzyme immunoassay. RESULTS: HBV cleared infection (both anti-HBc/anti-HBs+), chronic inactive/immune controlled HBV infection (anti-HBc + only), previous HBV vaccination (anti-HBs + only), active HBV infection (HBsAg+), individuals susceptible to HBV, and anti-HCV reactivity were found in 12.9, 1.8, 27.2, 0.5, 57.7, 1.2% in Amerindians and 12.1, 2.0, 37.1, 0.3, 55.4, 0.3% in non-Amerindians respectively. Out of 139 anti-HBc reactive individuals, 70 were anti-HBe reactive and none presented HBeAg or anti-HBc IgM. Anti-HBc prevalence was associated to older age (p < 0.0001). Overall anti-Delta prevalence was 0.3% and regarding anti-HBc reactive individuals, anti-delta prevalence was 3.4 and 0% in Amerindians and non-Amerindians respectively. CONCLUSIONS: Overall low prevalence of HBV and HCV infection was found in the populations studied, but high HBV and HCV prevalence was observed in Amerindians compared to non-Amerindians suggesting that these individuals have a higher likelihood of acquiring to these infections. Anti-delta antibodies were found among Amerindians from Eastern Amazon suggesting a risk for this population. Of note is that nearly half of Amerindians had no anti-HBs, indicating a need for HBV vaccination campaigns in this population.

Examining Hepatitis, A and B Vaccination, and HBV Reactivation Monitoring During Direct-Acting Antiviral Therapy for Hepatitis C.

The objective of this study was to examine Hepatitis A (HAV) and Hepatitis B (HBV) screening, and the risk of HBV reactivation during Hepatitis C (HCV) therapy with direct-acting antivirals (DAAs). A retrospective chart review was performed of patients treated with second generation DAA therapy from January 2014 to September 2016 at the Iowa City VA Healthcare System. In total 409 patients initiated HCV treatment, 308 (75%) and 241 (59%) were HAV and HBV vaccine eligible, respectively. Among those, 24 (8%) received a HAV vaccine, while only 20 (8%) received a HBV vaccine. Of these, 7 patients initiating an immunization in the clinic had record of completing the series. Further, 101 patients had a reactive Hepatitis B core Antibody indicating previous HBV infection, and 3 of these were tested for HBV reactivation during HCV therapy. Overall, the assessment found low rates of HAV and HBV vaccine administration, indicating missed opportunities for preventative care during HCV therapy. With the known risk of HBV reactivation with DAAs, the need for HAV and HBV screening is essential.

Detection of occult hepatitis B in serum and oral fluid samples.

In occult hepatitis B infection (OBI), hepatitis B virus DNA (HBV DNA) can be detected in serum samples; however, oral fluid collection for detection of HBV DNA has not yet been explored, despite the availability of collection devices. Serum and oral fluid samples from 45 hepatitis B core antibody (anti-HBc)-positive patients were collected for the amplification of the HBV polymerase gene. HBV DNA was detected in five serum and four oral fluid samples (the detection limit for oral fluid was 1.656 log IU/mL in paired serum). In conclusion, simple methodologies of sample collection and in-house polymerase chain reaction (PCR) allowed detection of HBV DNA, and these could be used to improve the diagnosis of OBI, especially in locations with limited resources.

Plasmonic Hepatitis B Biosensor for the Analysis of Clinical Saliva.

A biosensor for the detection of hepatitis B antibodies in clinical saliva was developed. Compared to conventional analysis of blood serum, it offers the advantage of noninvasive collection of samples. Detection of biomarkers in saliva imposes two major challenges associated with the low analyte concentration and increased surface fouling. The detection of minute amounts of hepatitis B antibodies was performed by plasmonically amplified fluorescence sandwich immunoassay. To have access to specific detection, we prevented the nonspecific adsorption of biomolecules present in saliva by brushes of poly[(N-(2-hydroxypropyl) methacrylamide)-co-(carboxybetaine methacrylamide)] grafted from the gold sensor surface and post modified with hepatitis B surface antigen. Obtained results were validated against the response measured with ELISA at a certified laboratory using serum from the same patients.

Assessment of the HBV vaccine response in a group of HIV-infected children in Morocco.

BACKGROUND: Since its development in the early 1980s, Hepatitis B virus (HBV) vaccine has been proven to be highly protective. However, its immunogenicity may be ineffective among HIV-infected children. In Morocco, HBV vaccine was introduced in 1999, and since then all infants, including vertically HIV-infected infants, have been following the vaccination schedule, implemented by the Moroccan ministry of health. An assessment of the immunization of these children is important to optimize efforts aimed at tackling Hepatitis B coinfection, within the country. METHODS: Forty-nine HIV-infected children (HIV group) and 112 HIV uninfected children (control group) were enrolled in this study. Samples were tested by Elisa (Monolisa Anti-HBs, Biorad) to quantify the anti-HBs antibodies. The % of lymphocyte subsets i.e. CD4+ T cells, CD8+ T cells, B cells, and NK, was determined by flow cytometry, using CellQuest Pro software (Becton-Dickinson), and for HIV group, HIV viral load was measured by real time PCR assay (Abbott). All variables were statistically compared in the two groups. RESULTS: The median age was 51 ± 35 months for the HIV group and 50 ± 36 months (p > 0.05) for the control group. Female represented 63% and 41% (p = 0.01), among the HIV group and the control group, respectively. Among HIV-infected children, 71.4% (35/49) were under HAART therapy at the enrollment in the study. Seroprotection titer i.e. anti-HBs ≥10mUI/ml among control group was 76% (85/112), and only 29% (14/49) among the perinatally HIV-infected children (p < 0.0001). Lower % of CD4 + T cells was observed in HIV-infected children with a poor anti-HBs response. CONCLUSION: In this studied group, we have shown that despite the vaccination of HIV-children with HBV vaccine, 71% did not show any seroprotective response. These findings support the need for monitoring HBV vaccine response among HIV-infected children in Morocco, in order to revaccinate non-immunized children.

Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues.

OBJECTIVE: The investigation regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) during chronic hepatitis B (CHB) treatment is limited. The aim of this study was to determine the performance of anti-HBc as a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive CHB patients treated with peginterferon (Peg-IFN) or nucleos(t)ide analogues (NUCs), respectively. DESIGN: This was a retrospective cohort study consisting of 231 and 560 patients enrolled in two phase IV, multicentre, randomised, controlled trials treated with Peg-IFN or NUC-based therapy for up to 2 years, respectively. Quantitative anti-HBc evaluation was conducted for all the available samples in the two trials by using a newly developed double-sandwich anti-HBc immunoassay. RESULTS: At the end of trials, 99 (42.9%) and 137 (24.5%) patients achieved HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. We defined 4.4 log10 IU/mL, with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict HBeAg seroconversion for both Peg-IFN and NUC. Patients with baseline anti-HBc ≥4.4 log10 IU/mL and baseline HBV DNA <9 log10 copies/mL had 65.8% (50/76) and 37.1% (52/140) rates of HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. In pooled analysis, other than treatment strategy, the baseline anti-HBc level was the best independent predictor for HBeAg seroconversion (OR 2.178; 95% CI 1.577 to 3.009; p<0.001). CONCLUSIONS: Baseline anti-HBc titre is a useful predictor of Peg-IFN and NUC therapy efficacy in HBeAg-positive CHB patients, which could be used for optimising the antiviral therapy of CHB.

Screening rate for hepatitis B virus infection in patients undergoing chemotherapy in Japan.

BACKGROUND: The aim of this study was to investigate the screening rate for hepatitis B virus (HBV) infection, which is recommended by some guidelines for the prevention of HBV reactivation, in patients undergoing chemotherapy for malignancy in Japan. METHODS: The study subjects were 3302 patients who had received first-line chemotherapy for malignancy from Apr 2008 through Mar 2013 utilizing the Claims Database of the Japan Medical Data Center. The proportion of patients who had been tested for HBsAg (P-HBsAg) and the proportion of HBsAg-negative patients who had undergone tests for anti-HBc and anti-HBs (P-HBc/HBsAb) before chemotherapy were investigated. RESULTS: P-HBsAg and P-HBc/HBsAb in all 3302 patients were 66.3 and 19.9 %, respectively. P-HBsAg in patients with solid tumors and those with hematological malignancies were 66.1 and 67.5 % (p = 0.61), respectively, and P-HBc/HBsAb were 12.3 and 75.8 % (p < 0.0001), respectively. P-HBsAg in patients from cancer centers and non-cancer centers were 66.9 and 65.5 % (p = 0.43), respectively, and P-HBc/HBsAb were 25.1 and 12.4 % (p < 0.0001), respectively. P-HBsAg in patients encountered before and after the announcement of the Japanese guideline were 51.3 and 67.1 % (p < 0.001), respectively, and P-HBc/HBsAb were 7.9 and 20.4 % (p = 0.01), respectively. CONCLUSIONS: The screening rate for HBV among cancer patients scheduled for chemotherapy remains unsatisfactory, especially in patients with solid tumors and those from non-cancer centers. Although the figures are improving after the announcement of the Japanese guideline, intensive measures to improve awareness about HBV reactivation during/after chemotherapy are needed.

Antibodies against Hepatitis A and Hepatitis B Virus in Intravenous Immunoglobulin Products.

The worldwide seroprevalence of hepatitis A virus (HAV) and hepatitis B virus (HBV) has changed over the last two decades, indicating a declining incidence of HAV and HBV infections. Therefore, vaccinations against HAV and HBV are recommended for unimmunized people before traveling to an endemic area. Unfortunately, primary antibody deficiency (PAD) patients can only obtain humoral immunity through intravenous immunoglobulin G (IVIG) replacement and not from vaccination because of a defect in antibody production. However, few studies have analyzed the titers of antibodies against HAV or HBV in IVIG products. In this study, the titers of anti-HAV and anti-HBs antibodies were measured in nineteen lots of IVIG products from five manufacturers from three countries (A, B from Korea; C, D from Japan; and E from the USA), and trough titers in plasma were estimated. Concentrations of anti-HAV antibody ranged from 1,888-8,927 mIU/mL and estimated trough titers exceeded the minimal protective value in all evaluated IVIG products. Concentrations of anti-HBs antibody ranged from 438-965 mIU/mL in products A and B and were 157, 123, and 1,945 mIU/mL in products C, D, and E, respectively. Estimated trough titers in products A, B, and E exceeded the minimal protective value but those in products C and D did not reach this threshold. These data demonstrated that available IVIG products generally provide sufficient antibodies against HAV and HBV to protect patients with PAD, although the trough concentrations of anti-HBs antibody in two IVIG products did not reach the minimum protective value.

Evaluation of seroprevalence of Hepatitis B virus infection among patients attending a hospital of semi-urban North India using rapid immunoassay test.

BACKGROUND: Viral hepatitis is a serious public health problem with hepatitis B virus (HBV) being one of its principle causes affecting billions of people globally. The laboratory diagnosis of HBV infection is made by detection of hepatitis B surface antigen (HBsAg) in serum. OBJECTIVE: The present study was done to evaluate the seroprevalence of hepatitis B infection among patients attending a hospital at a semi-urban North India using rapid immunoassay test kit. MATERIALS AND METHODS: A total of 1537 patients were included in the study whose venous blood samples were collected, and serum was tested for the presence of HBsAg using a rapid one-step immunoassay test kit. RESULTS: Out of 1537 patients whose blood samples were tested, 61 were found to be reactive to HBsAg giving the prevalence to be 3.9%, with 49 males and 12 females. Out of 61 reactive patient's majority belonged to inpatient (82.0%) as compared to outpatient department (18.0%). The majority of the reactive patients belonged to age group 28-37 years (37.7%), belonged to rural areas (86.9%), were illiterate (67.2%), were skilled workers (63.9%) and belonged to socioeconomic Class 4 (50.8%). Among the reactive patients, the most frequent suspected risk factor for hepatitis B infection was found to be visiting a community barber (19.7%). CONCLUSION: HBV infection is a dreadful disease, and its accurate and timely diagnosis using rapid immunoassay test kit is useful as it gives an indication about its seroprevalence in a given geographical area even with limited resources.