The viral hepatitis B care cascade: A population-based comparison of immigrant groups.

BACKGROUND AND AIMS: The global burden of viral hepatitis B is substantial, and monitoring infections across the care cascade is important for elimination efforts. There is little information on care disparities by immigration status, and we aimed to quantify disease burden among immigrant subgroups. APPROACH AND RESULTS: In this population-based, retrospective cohort study, we used linked laboratory and health administrative records to describe the HBV care cascade in five distinct stages: (1) lifetime prevalence; (2) diagnosis; (3) engagement with care; (4) treatment initiation; and (5) treatment continuation. Infections were identified based on at least one reactive antigen or nucleic acid test, and lifetime prevalence was estimated as the sum of diagnosed and estimated undiagnosed cases. Care cascades were compared between long-term residents and immigrant groups, including subgroups born in hepatitis B endemic countries. Stratified analyses and multivariable Poisson regression were used to identify drivers for cascade progression. Between January 1997 and December 2014, 2,014,470 persons were included, 50,475 with infections, of whom 30,118 were engaged with care, 11,450 initiated treatment, and 6554 continued treatment >1 year. Lifetime prevalence was estimated as 163,309 (1.34%) overall, 115,722 (3.42%) among all immigrants, and 50,876 (9.37%) among those from highly endemic countries. Compared to long-term residents, immigrants were more likely to be diagnosed (adjusted rate ratio [aRR], 4.55; 95% CI, 4.46, 4.63), engaged with care (aRR, 1.07; 95% CI, 1.04, 1.09), and initiate treatment (aRR, 1.09; 95% CI, 1.03, 1.16). CONCLUSIONS: In conclusion, immigrants fared well compared to long-term residents along the care cascade, having higher rates of diagnosis and slightly better measures in subsequent cascade stages, although intensified screening efforts and better strategies to facilitate linkage to care are still needed.

Quantitative assessment of LPS-HBsAg interaction by introducing a novel application of immunoaffinity chromatography.

Lipopolysaccharide (LPS), as a stubborn contamination, should be monitored and kept in an acceptable level during the pharmaceutical production process. Recombinant hepatitis B surface antigen (r-HBsAg) is one of the recombinant biological products, which is probable to suffer from extrinsic endotoxin due to its long and complex production process. This research aims to assess the potential interaction between LPS and r-HBsAg by recruiting immunoaffinity chromatography (IAC) as a novel tool to quantify the interaction. Molecular modeling was performed on the HBsAg molecule to theoretically predict its potential binding and interaction sites. Then dynamic light scattering (DLS) analysis was implemented on HBsAg, LPS, and mixtures of them to reveal the interaction. The virus-like particle (VLP) structure of HBsAg and the ribbon-like structure of LPS were visualized by transmission electron microscopy (TEM). Finally, the interaction was quantified by applying various LPS/HBsAg ratios ranging from 1.67 to 120 EU/dose in the IAC. Consequently, the LPS/HBsAg ratios in the eluate were measured from 1.67 to a maximum of 92.5 EU/dose. The results indicated that 77 to 100% of total LPS interacted with HBsAg by an inverse relationship to the incubated LPS concentration. The findings implied that the introduced procedure is remarkably practical in the quantification of LPS interaction with a target recombinant protein.

Current and Past Infections of HBV Do Not Increase Mortality in Patients With COVID-19.

BACKGROUND AND AIMS: We compared risk of acute liver injury and mortality in patients with COVID-19 and current, past, and no HBV infection. APPROACH AND RESULTS: This was a territory-wide retrospective cohort study in Hong Kong. Patients with COVID-19 between January 23, 2020, and January 1, 2021, were identified. Patients with hepatitis C or no HBsAg results were excluded. The primary outcome was mortality. Acute liver injury was defined as alanine aminotransferase or aspartate aminotransferase ≥2 × upper limit of normal (ULN; i.e., 80 U/L), with total bilirubin ≥2 × ULN (i.e., 2.2 mg/dL) and/or international normalized ratio ≥1.7. Of 5,639 patients included, 353 (6.3%) and 359 (6.4%) had current and past HBV infection, respectively. Compared to patients without known HBV exposure, current HBV-infected patients were older and more likely to have cirrhosis. Past HBV-infected patients were the oldest, and more had diabetes and cardiovascular disease. At a median follow-up of 14 (9-20) days, 138 (2.4%) patients died; acute liver injury occurred in 58 (1.2%), 8 (2.3%), and 11 (3.1%) patients with no, current, and past HBV infection, respectively. Acute liver injury (adjusted HR [aHR], 2.45; 95% CI, 1.52-3.96; P < 0.001), but not current (aHR, 1.29; 95% CI, 0.61-2.70; P = 0.507) or past (aHR, 0.90; 95% CI, 0.56-1.46; P = 0.681) HBV infection, was associated with mortality. Use of corticosteroid, antifungal, ribavirin, or lopinavir-ritonavir (adjusted OR [aOR], 2.55-5.63), but not current (aOR, 1.93; 95% CI, 0.88-4.24; P = 0.102) or past (aOR, 1.25; 95% CI, 0.62-2.55; P = 0.533) HBV infection, was associated with acute liver injury. CONCLUSION: Current or past HBV infections were not associated with more liver injury and mortality in COVID-19.

Surgical plume from tissue infected with human hepatitis B virus can contain viral substances.

INTRODUCTION: Evidence on the biological danger associated with surgical plume is lacking. We examined whether surgical plume, generated by the energy devices ultrasonically activated scalpel (US) or electrocautery (EC) contains virus-related substances. MATERIAL AND METHODS: Experiment 1, ex-vivo model: Tumor mass of a hepatocellular carcinoma line was prepared in a Nod/SCID mouse. Surgical plume generated on the mass by US or EC was collected and detection of HBs gene fragment and antigens (HBsAg or AFP) was conducted. Experiment 2, clinical specimen: Detection of HBV-DNA and HBsAg was conducted following the collection of surgical plume generated from clinically obtained liver specimens from six HBV-associated hepatocellular carcinoma patients. RESULTS: Experiment 1: HBs gene fragment was detected in the solutions regardless of the device used. HBsAg was detected in US and EC solutions and AFP was also detected in a US solution. Experiment 2: HBV-DNA was detected in both devices, in all three cases whose preoperative serum HBV-DNA was positive. In the other serum-negative cases, HBV-DNA was not detected. While serum HBsAg was positive in five of six cases, it was not detected in any solution. CONCLUSIONS: DNA fragments or antigens of virus can exist in the surgical plume generated by EC or US.

Generation of HBsAg DNA aptamer using modified cell-based SELEX strategy.

Aptamers as potential alternatives for antibodies could be employed against hepatitis B surface antigen (HBsAg), the great hallmark and first serological marker in HBV, for further theragnostic applications. Therefore, isolation HBsAg specific aptamer was performed in this study with a modified Cell-SELEX method. HEK293T overexpressing HBsAg and HEK293T as target and control cells respectively, were incubated with single-stranded rounds of DNA library during six SELEX and Counter SELEX rounds. Here, we introduced the new modified Cell-SELEX using deoxyribonuclease I digestion to separate single stranded DNA aptamers against the HBsAg. Characterization and evaluation of selected sequences were performed using flow cytometry analysis. The results led to isolation of 15 different ssDNA clones in six rounds of selection which were categorized to four clusters based on common structural motifs. The evaluation of SELEX progress showed growth in aptamer affinity with increasing in the cycle number. Taken together, the application of modified cell-SELEX demonstrated the isolation of HBsAg-specific ssDNA aptamers with proper affinity. Modified cell-SELEX as an efficient method can shorten the selection procedure and increase the success rate while the benefits of cell-based SELEX will be retained. Selected aptamers could be applied in purification columns, diagnostic kits, and drug delivery system against HBV-related liver cancer.

Factors Associated With Hepatitis B Exposure Among People Who Report Using Methamphetamine: National Health and Nutrition Examination Survey 2009-2016.

BACKGROUND: With the nation's focus on the opioid crisis, methamphetamine has made a comeback, potentially increasing risk for hepatitis B. We examined factors associated with hepatitis B virus (HBV) exposure among people who reported ever using methamphetamine in a nationally representative survey. METHODS: We used the National Health and Nutrition Examination Survey to examine factors associated with HBV exposure among participants who reported ever using methamphetamine using bivariate and multivariable logistic regression. RESULTS: Overall, 847 participants met the study inclusion criteria. In multivariable logistic regression, female sex (adjusted odds ratio, 3.83; 95% confidence interval, 1.65-8.90), living below the poverty threshold (3.17; 1.39-7.21), injection drug use (4.89; 1.95-12.26), active hepatitis C virus infection (3.39; 1.10-12.26), and identifying as men who have sex with men (28.21; 5.19-153.38) were significantly associated with HBV exposure. CONCLUSIONS: The odds of HBV exposure for female participants who reported using methamphetamine were 4 times than that for male participants. Poverty, injection drug use, and hepatitis C virus infection were also associated. As methamphetamine use increases, it is critical to identify those at risk of acquiring HBV infections in order to target testing and vaccination.

Evaluation of Hepatitis B Reactivation Among Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors.

Hepatitis B reactivation (HBVr) in cancer patients is a well-established complication due to chemotherapy-induced immunosuppression. Studies have reported HBVr associated with immunosuppressive medications, such as rituximab, methotrexate, and high dose steroids. There are different risks for different types of chemotherapy with rituximab carrying one of the highest risks for hepatitis B reactivation. Tyrosine kinase inhibitors (TKIs) are the standard of care in patients with chronic myeloid leukemia (CML). The risk of HBVr in chronic myeloid leukemia has been reported in many studies, but to this date, there are no clear guidelines or recommendations regarding screening and monitoring of HBV in CML patients receiving TKIs. We conducted this review to identify the risk of HBVr in patients with CML who are treated with tyrosine kinase inhibitors. We recommend testing for HBV status in patients who are to be treated with TKIs and to consider giving prophylaxis in those who are positive for HBsAg at baseline. More studies are needed to assess the risk of reactivation in patients with Hepatitis B core antibody positive receiving TKIs. Currently, monitoring such patients for reactivation may be the best strategy.

Risk of hepatitis B reactivation in hepatitis B surface antigen seronegative and core antibody seropositive kidney transplant recipients.

BACKGROUND: Previous contact with Hepatitis B virus (HBV) is common in patients undergoing hemodialysis. Literature has shown conflicting results on the risk of HBV reactivation in kidney transplant (KT) recipients with serologic evidence of past HBV infection. METHODS: We reviewed 631 consecutive KT recipients and selected 70 patients simultaneously HBsAg negative and anti-HBc positive before KT, regardless of hepatitis B surface antibody (anti-HBs) status. Demographic characteristics, coinfection with other viruses, the presence of a previous KT, induction and maintenance immunosuppression, length of follow up, biopsy-proven acute rejection episodes, incidence of impaired liver function, and causes of graft loss and mortality were collected. Hepatitis B virus reactivation was defined as detection of HBV DNA viral load >2000 IU/mL during follow up. Outcome data included HBV reactivation episodes, graft function, and patient survival. RESULTS: Median follow-up was 151 months; 91.4% of patients were positive to anti-HBs prior to KT. No patient received HBV prophylaxis and 11 patients (15.7%) received rituximab as part of induction therapy. Anti-HBs titers remained stable in all patients throughout the observation period but two patient showed evidence of HBV reactivation after KT. CONCLUSION: Hepatitis B virus reactivation in HBsAg-negative and anti-HBc-positive after KT is rare but possible. We suggest evaluating HBV serologies, HBV DNA viral load, and liver enzymes before KT and routinely monitoring serologic HBV markers after KT. As only two patients experienced HBV reactivation, it is neither possible to define risk factors for HBV reactivation nor to evaluate the impact of different immunosuppressants or the benefit of prophylactic regimens. Further studies regarding HBV reactivation in solid organ transplant recipients are necessary.

Nucleic acid amplification test: Bridging the gap in blood safety & re-evaluation of blood screening for cryptic transfusion-transmitted infection among Indian donors.

Background & objectives: : Nucleic acid amplification test (NAT) in blood donor screening not only detects window period (WP) donors but also those with chronic occult infections which are negative by routine serological screening. This study was conducted to determine the time trend of NAT positivity and seroprevalence of transfusion-transmitted infections (TTIs) through a period of six years and evaluate the strength of NAT as a supplementary test in identifying the cryptic carriers in blood donor population. Methods: : A total of 1,01,411 blood donations were screened between January 2011 and December 2016 by the ELISA and individual donor (ID) NAT Procleix Ultrio Plus Assay. Additional molecular and serological assays were done on the NAT yield samples to differentiate the type of cryptic carriers. Results: : NAT yields comprised 0.05 per cent (50/101411) of the total samples tested with a yield rate of 1/2028. Hepatitis B virus (HBV) contributed to 80 per cent of the total NAT yields and the rest 20 per cent due to hepatitis C virus (HCV). Majority of HBV NAT yields (75%) were from chronic occult donors and 25 per cent were WP donors. Both HBV and HCV NAT yields had a wide range of viral count. There was no HIV NAT yield. A significant decline in the prevalence rate of TTIs through the study period of six years was observed. Interpretation & conclusions: : The cryptic infections found in blood donors increase the risk of TTIs. Blood screening by both serology and NAT can reduce this threat.

Pattern and predictors of medical care received by hepatitis B carriers during pregnancy and after delivery.

OBJECTIVE: The objective of the study is to evaluate the pattern and predictors of medical care received by hepatitis B virus (HBV) carriers during pregnancy and after delivery in Hong Kong. STUDY DESIGN: The study is a retrospective analysis. METHODS: Pregnant HBV carriers and their infants were followed up for 9-12 months after delivery. Face-to-face interviews were conducted to investigate what medical care they received for HBV before, during and after pregnancy. RESULTS: Data were available for 412 HBV carriers. A total of 375 (91.0%) women were known HBV carriers before pregnancy. Routine antenatal screening picked out the remaining 37 (9.0%) HBV carriers; these women were younger, more likely to be smokers and had a lower level of education (P < 0.05) than known HBV carriers. In total, 356 of 412 (86.4%) HBV carriers did not receive any medical care for HBV during pregnancy. Known HBV carrier status, history of medical check-up and the use of antiviral treatment before pregnancy were significant predictors for HBV medical care during pregnancy (P < 0.05). The results show that 217 of 412 (52.6%) HBV carriers did not receive medical care for HBV after delivery. HBV medical care before pregnancy, use of antiviral treatment before pregnancy and a higher level of education were significant predictors for postpartum HBV medical care (P < 0.05). Multivariate analysis showed that HBV medical care before pregnancy (odds ratio [OR], 7.73; 95% confidence interval [CI], 3.21-18.65; P < 0.001) and the use of antiviral treatment (OR, 5.02; 95% CI, 1.41-17.81; P = 0.013) were associated with medical care during pregnancy. Medical care before pregnancy was also associated with postpartum HBV medical care (OR, 5.05; 95% CI, 3.29-7.51; P < 0.001). CONCLUSIONS: A significant proportion of HBV carriers did not receive HBV-related medical check-ups during and after pregnancy in Hong Kong despite the majority being aware of their carrier status. Medical care before pregnancy predicted antenatal and postpartum HBV medical care.

Application of hydrocyclone for separation of Pichia pastoris produced r-HBsAg from fermentation culture: impact of concentration and pressure on hydrocyclone performance.

Separation of biomass from culture media by centrifugation and then washing the biomass are mandatory steps in the fermentation process of recombinant Pichia pastoris expressed HBsAg intracellularly. Biomass has to be washed many times to eliminate the culture media residues thoroughly. In this study, we tried to develop the hydrocyclone as an alternative method for separation of biomass from fermentation culture, an attractive replacement for centrifugation processes. The advantages of using hydrocyclone in biomass separation could be summarized in its suitability for continuous separation and its low risk of contamination. To evaluate the performance of hydrocyclone, concentration ratio in underflow to feed stream, capacity, and centrifugal force by considering three parameters of pressure drop, concentration, and the type of hydrocyclone were investigated. Using three level factorial design a concentration ratio equation was developed, with the correlation coefficient R2 = 0.977 ensured the good fitness of the predicted data with the experimental results. In optimal conditions, maximum concentration ratio was 1.246, for flow rate 13.5 LPM and C-force equal to 1276.11 at maximum pressure drop (3 bar) and minimum concentration (0.5% w/w) in hydrocyclone 1. Herein, two different hydrocyclones with the cylindrical diameters of 19 mm and 21 mm were used for separating the yeast cells.

Integration of size-exclusion chromatography and ultracentrifugation for purification of recombinant hepatitis B surface antigen: An alternative method for immunoaffinity chromatography.

In purification process of recombinant hepatitis B surface antigen (rHBsAg), immunoaffinity chromatography (IAF) is one of the most important and effective steps in rHBsAg purification. However, the buffer composition and the interaction of ligands-rHBsAg often lead to disassembly, deformation, and clumping of a portion of these virus-like particles (VLPs). Besides, the expensive media, variable biospecific ligand density and the possibility of product contamination are other reported drawbacks of using IAF which makes the production process of rHBsAg more challenging. This study investigated the possibility of substituting IAF with purification methods of size-exclusion chromatography (SEC) and ultracentrifugation. In the SEC, the efficacy of rHBsAg purification was examined by four different media in which Toyopearl HW 65S resin demonstrated the best results. By integrating Toyopearl HW 65S resin - with a bed height of 51 cm - and ultracentrifugation process at 47,000 rpm for 48 hr, 95% of protein impurities were removed. Compared to the IAF in rHBsAg production, the purified sample contained a higher percentage of multimeric rHBsAg particles without any noticeable monomer and aggregate forms. The result of this study indicates that the proposed integrated system could be an efficient mild purification alternative for conventional IAF.

A novel general and efficient technique for dissociating antigen in circulating immune complexes.

Circulating immune complexes (CICs) are produced during the immune response. It is more clinically important to establish a general and efficient CICs dissociation technique for the detection of antigens for CICs other than the detection of free antigens in the serum. Polyethylene glycol (PEG) two-precipitation separation and glycine-HCl as a buffer system were employed to develop a general and efficient buffer dissociation technique to separate CICs from serum and dissociate antigens from CICs. The measurement value of new PEG two-precipitation separation technique was higher than traditional PEG precipitation separation technique. There were slight differences in the dissociation conditions of HCV Core-IC, HIV P24-IC, Ins-IC and TG-IC as compared to HBsAg-IC. The detection of antigens in HBsAg-IC, HCV Core-IC, HIV P24-IC, Ins-IC and TG-IC with this technique was superior to that with HCl Dissociation, Trypsin Digestion or Immune Complex Transfer technique. PEG two-precipitation dissociation technique may reduce macromolecular protein and the adhesion of free antigens during the co-precipitation, which increases the efficiency of separation and precipitation of CICs. This technique also avoids the damage of reagents to antigens, assuring the repeatability, reliability and validity. Thus, this technique is application in samples negative or positive for free antigens.

Isolation of recombinant Hepatitis B surface antigen with antibody-conjugated superparamagnetic Fe3O4/SiO2 core-shell nanoparticles.

In the production process of recombinant Hepatitis B surface antigen (rHBsAg) various separation techniques are used to purify this virus-like particle (VLP). In this study, we developed antibody-conjugated super-paramagnetic Fe3O4/SiO2 core-shell nanoparticles as a highly selective method for isolation of expressed rHBsAg in yeast Pichia pastoris. For this purpose, first, iron oxide magnetic nanoparticles (MNPs) were prepared by co-precipitation method in alkali media and coated with silica. Then the surface was activated by amine groups and conjugated with oxidized antibodies. X-ray diffraction (XRD), transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM) were used to study the physical properties of MNPs. To evaluate the efficacy of these MNPs as a purification technique successfully synthesized MNPs were added to the rHBsAg sample to couple with the antigen and then be isolated based on their magnetic property. In the present research, in the optimum condition, we could isolate 65% of total rHBsAg from the final vaccine sample with purity above 95%. In this procedure, the maximum obtained specific yield (mg HBsAg/mg MNPs) was equal to 37.6. These results underline the potential application of the immune-magnetic separation (IMS) in the future bioseparation systems.

Enhancing recovery of recombinant hepatitis B surface antigen in lab-scale and large-scale anion-exchange chromatography by optimizing the conductivity of buffers.

In biopharmaceutical science, ion-exchange chromatography (IEC) is a well-known purification technique to separate the impurities such as host cell proteins from recombinant proteins. However, IEC is one of the limiting steps in the purification process of recombinant hepatitis B surface antigen (rHBsAg), due to its low recovery rate (<50%). In the current study, we hypothesized that ionic strengths of IEC buffers are easy-to-control parameters which can play a major role in optimizing the process and increasing the recovery. Thus, we investigated the effects of ionic strengths of buffers on rHBsAg recovery via adjusting Tris-HCl and NaCl concentrations. Increasing the conductivity of equilibration (Eq.), washing (Wash.) and elution (Elut.) buffers from their initial values of 1.6 mS/cm, 1.6 mS/cm, and 7.0 mS/cm to 1.6 mS/cm, 7 mS/cm and 50 mS/cm, respectively yielded an average recovery rate of 82% in both lab-scale and large-scale weak anion-exchange chromatography without any harsh effect on the purity percentage of rHBsAg. The recovery enhancement via increasing the conductivity of Eq. and Wash. buffers can be explained by their roles in reducing the binding strength and aggregation of retained particles in the column. Moreover, further increase in the salt concentration of Elut. Buffer could substantially promote the ion exchange process and the elution of retained rHBsAg.

Improving the recovery of clarification process of recombinant hepatitis B surface antigen in large-scale by optimizing adsorption-desorption parameters on Aerosil-380.

In the downstream process of recombinant hepatitis B surface antigen (rHBsAg), nano-colloidal silica adsorbent (Aerosil-380) is one of the possible methods to separate the antigen from other main impurities partially. The current study aimed to maximize the adsorptive capacity of Aerosil-380 as well as rHBsAg recovery for large-scale production of recombinant hepatitis B vaccine. The experimental design methodology was used to optimize the eight critical parameters influencing the efficiency, rHBsAg recovery, of the adsorption-desorption process in the lab-scale. These examined parameters were the adsorption-desorption temperature, pH, contact time, agitation speed, antigen concentration, and desorption buffer. Under optimal condition, the maximum adsorption capacity of Aerosil-380 was equal to 3333 µg.g-1 (rHBsAg/adsorbent), and we could recover about 95% of rHBsAg with purity of 54% (rHBsAg/total protein) in the lab scale. Using the optimum parameters for rHBsAg clarification process in large-scale by Aerosil-380, we recovered about 78% of rHBsAg with 43% purity. Based on the obtained experimental data, Langmuir adsorption isotherm and pseudo-first-order kinetic model provide the best correlations of experimental data for the adsorbent. Findings of this study significantly increase the recovery of clarification process of rHBsAg in large-scale compared to previous reports.

Large-scale purification of recombinant hepatitis B surface antigen from Pichia pastoris with non-affinity chromatographic methods as a substitute to immunoaffinity chromatography.

The costly media, inconsistent ligand density, ligand leakage, and possible destabilization of recombinant hepatitis B surface antigen (rHBsAg) particles are main drawbacks of using immunoaffinity chromatography (IAF) in the large-scale downstream processing. In this study, we aimed to use an efficient large-scale purification system as an alternative purification method for immunoaffinity chromatography. For this purpose, we suggested integrating non-affinity chromatographic methods of hydrophobic interaction chromatography (HIC) and size-exclusion chromatography (SEC) for cost-effective purification of rHBsAg expressed in P. pastoris. The optimization of such process is not trivial and straightforward since diverse molecular characteristics of expressed rHBsAg in each type of host cell cause different interactions in non-affinity chromatography processes. The working buffer composition and chromatography parameters are the most influential factors in hydrophobic interaction chromatography. The best result for lab-scale HIC was achieved by using ammonium sulfate buffer in 10% of saturation concentration in pH 7.0 with Butyl-S Sepharose 6 Fast Flow medium and with subsequent Tween-100 and urea elution. In this process, the recovery, purity, and total yield were about 84%, 82%, and 69%, respectively. By scaling-up the HIC and integrating it with Sephacryl S-400 SEC, we obtained highly pure, i.e., > 90%, rHBsAg virus-like particles (VLP).

[A typical investigation on the status of diagnosis and reporting of hepatitis B inpatients in non-surveillance hospitals in three provinces in China, 2015].

Objective: To review the consistency of diagnosis and reporting of hepatitis B (HB) patient in non-surveillance hospitals in three provinces and analyze the influencing factors. Methods: In 2016, using typical survey methods, we carried out a hospital-based pilot study in three provinces: Fujian, Hainan and Gansu. In each province, we chose two hospitals with grade 3 and grade 2 respectively in each province, using the following criteria: (1) in 2015, the hospital reported a greater number of hepatitis B cases compared the hospital-based provincial mean; (2) the hospital had an advanced laboratory information system (LIS) with access to HBsAg test results; (3) the hospital had an electronic hospital information system (HIS) which linked to the LIS via the inpatient medical record number; (4) general hospital; (5) non-surveillance hospitals for hepatitis B. Using national notifiable infectious disease reporting system (NNDRS), we chose all HB patients who were reported by the investigated hospitals in 2015, and we linked NNDRS HBV case-reports with patient-data from hospital information systems (HIS) to review the diagnosis, and then to compare the consistency of reviewed diagnosis and NNDRS report diagnosis, which we made a descriptive analysis. We used multivariable logistic regression to examine factors associated with misclassification of case-reports to NNDRS. Results: We found the NNDRS report accuracy was 47.11% (669) among 1 420 eligible inpatient hepatitis B inpatients. Of the 352 reported acute HBV cases, 6.53% (23) were consistent with our medical record review, the accuracy rate for level 2 hospitals and level 3 hospitals was 9.42% (21) and 1.55% (2), respectively. Of the1 068 reported chronic HBV cases, 60.49% (646) were consistent with our medical record review, the accuracy rate for level 2 hospitals and level 3 hospitals was 57.92% (106) and 60.02% (540), respectively. Compared to primary diagnosis of HB patients, the OR(95%CI) for mis-report was 29.36 (19.21-44.76) in non-primary diagnosis of HB patients. Compared to Fujian Province, the mis-report risk was higher in Hainan province and Gansu Province, with the values of OR (95%CI) being 2.33 (1.58-3.44) and 20.38 (11.29-36.78), respectively; compared to level 3 hospitals, the OR (95%CI) for mis-report was 2.38 (1.66-3.42) for level 2 hospitals; compared to HB related wards, the OR (95%CI) for mis-report was 1.45 (1.04-2.01) in non-HB-related wards. Conclusion: In some non-surveillance areas of China, the consistency between hepatitis B diagnosed in hospital and reported in NNDRS was low. Factors affecting the accuracy of HB surveillance data in NNDRS were level 2 hospitals, non-liver disease departments and nonprimary diagnosis of HB.

Hepatitis B virus infection is associated with younger median age at diagnosis and death in cancers.

Several non-hepatocellular cancers were linked with hepatitis B virus (HBV) infection. This study was aimed to quantify the potential associations between HBV infection and multiple non-hepatocellular cancers. Continuous cases, including 5,715 non-cancer and 40,963 cancer cases diagnosed from 2008 to 2014 in Sun Yat-sen University Cancer Center were analyzed. HBV DNA and hepatitis B core antigen (HBcAg) were examed in gastric cancer tissues by polymerase chain reaction and immunohistochemical staining. After adjusting for age, sex, year of diagnosis, smoking, drinking and family history of cancer, significant associations were found between serum HBsAg and frequently reported HBV-related non-hepatocellular cancers, including non-Hodgkin's lymphoma, cholangiocarcinoma and pancreatic cancer [adjusted odds ratio (AOR) and 95% confidence interval (CI): 1.89 (1.65-2.16)], as well as total other non-hepatocellular cancers [AOR and 95% CI: 1.12 (1.03-1.22)]. The median ages at diagnosis, all-cause death and cancer-specific death of serum HBsAg positive cancer patients were all significantly younger than those with serum HBsAg negative. HBV DNA was detected in 12.4% (34/275) gastric cancer tissues and HBcAg was most commonly detected in lymphocytes. This was the first report that HBV infection had a modest but significant nonspecific association with total non-hepatocellular cancers. Median age at diagnosis and death was significantly younger in serum HBsAg positive cancer patients. The underlying mechanism needs further investigation.

Active immunization for prevention of De novo hepatitis B virus infection after adult living donor liver transplantation with a hepatitis B core antigen-positive graft.

De novo hepatitis B virus (DNHB) infections may occur in recipients who do not receive prophylaxis after liver transplantation (LT) with antibody to hepatitis B core antigen (anti-HBc)-positive donor grafts. Active immunization has been shown to prevent DNHB in pediatric recipients. Our aim is to investigate the efficacy of HBV vaccination for preventing DNHB in adult living donor liver transplantation (LDLT). In total, 71 adult antibody to hepatitis B surface antigen (anti-HBs)-negative LDLT patients who received anti-HBc+ grafts from 2000 to 2010 were enrolled into this study. Patients were given hepatitis B virus vaccinations with the aim of achieving anti-HBs > 1000 IU/L before transplant and >100 IU/L after transplant. The cohort was stratified into 3 groups: patients with pretransplant anti-HBs titer of > 1000 IU/L without the need for posttransplant prophylaxis (group 1, n = 24), patients with pretransplant low titer of <1000 IU/L who were given posttransplant lamivudine prophylaxis and responded appropriately to posttransplant vaccination by maintaining anti-HBs titers of > 100 IU/L (group 2, n = 30), and low titer nonresponders (anti-HBs titer of < 100 IU/L despite vaccination), for whom lamivudine was continued indefinitely (group 3, n = 17). All DNHB occurred in group 3 patients with posttransplant anti-HBs levels of < 100 IU/L, with an incidence rate of 17.6% compared with 0% in patients with posttransplant anti-HBs levels of > 100 IU/L (P = 0.001). A pretransplant anti-HBs level of >1000 IU/L was significantly associated with early attainment and a sustained level of posttransplant anti-HBs of >100 IU/L (P < 0.001). Active immunization is effective in preventing DNHB in adult LDLT if the posttransplant anti-HBs level is maintained above 100 IU/L with vaccination. Antiviral prophylaxis can be safely discontinued in patients who obtain this immunity. Liver Transplantation 23 1266-1272 2017 AASLD.