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To assess the seroprevalence of Hepatitis B (HBV), Hepatitis C (HCV), and Human Immunodeficiency Virus (HIV) among newly admitted health track students in a large university in the Eastern Province of Saudi Arabia, and determine the students' immunity against HBV, and bloodborne viral infection risk factors or practices among them.Information about the 1145 students, vaccination history, and exposure to bloodborne viral infections risk factors/practices were collected using a structured questionnaire during August 2020. The results of serological data were obtained from students' electronic files.All students tested negative for HBV, HCV, and HIV infections. The seroprevalence of positivity against HBV was 25.8%, and the frequencies of students with protective levels of anti-HBV were inversely related to their age. The majority (70.8%) of students had 1 or 2 identifiable risk factors for bloodborne diseases, and the most frequent risk factor was history of dental intervention. Female students were more than four-times likely to be in the high-risk group for bloodborne infections than males (OR = 4.4; 95% CI: 3.3-5.9). Being from the Central Province of Saudi Arabia (OR = 1.9; 95% CI: 1.2-3.1) and having a mother's educational level of master or doctorate (OR = 3.0; 95% CI: 1.3-6.7) were found to be independent predictors of being in the high-risk group. On the other hand, having a family member in the healthcare field was found as a predictor of being in the low-risk group for bloodborne diseases (OR = 0.7; 95% CI: 0.5-0.9).About three-fourth of students in this study were susceptible to HBV. Our findings stress the need to develop policies to raise awareness regarding bloodborne infectious diseases, in addition to expanding access to HBV vaccination for healthcare staff, especially in older ages.

Background and Aims This retrospective study aimed to investigate the impact of positive hepatitis B core antibody (anti-HBc) and metabolic disorders on clinical characteristics of hepatocellular carcinoma (HCC) patients in an HBV-endemic area. Methods A total of 1950 consecutive patients newly diagnosed with HCC between 2002 and 2015 were included. Patient records were reviewed. We compared non-viral and non-alcoholic HCC patients with other etiological groups for HCC. In addition, we compared HCC patients with negative hepatitis B surface antigen (HBsAg) and positive anti-HBc to those with negative HBsAg and negative anti-HBc, and to those with HBV. Results The prevalence of non-viral and non-alcoholic HCC increased from 7% in 2002–2011 to 12% in 2012–2015. The proportion of non-viral and non-alcoholic HCC gradually increased with age. Patients with non-viral and non-alcoholic HCC exhibited higher rates of metabolic disorders and preserved liver function. The rate of anti-HBc positivity was similarly high in all HCC etiological groups. The clinical features of HCC patients with negative HBsAg and positive anti-HBc were similar to those with negative HBsAg and negative anti-HBc, but significantly different from those with HBV HCC. Regarding tumor characteristics, patients in the non-viral and non-alcoholic HCC group had more advanced stages of tumors (mUICC stage III–V and BCLC stage C/D). There was no significant difference in overall survival among the patient groups. The presence of anti-HBc did not affect patient survival. Conclusion Patients with non-viral and non-alcoholic HCC had a relatively high prevalence of metabolic disorders and preserved liver function. However, they had advanced tumor stage compared to patients from other etiological groups. Anti-HBc positivity did not affect the clinical characteristics or prognosis of non-HBV HCC patients in this study.

Background Chronic hepatitis B is a highly heterogeneous disease that can be divided into four phases: Immune tolerant (IT), immune active (IA), inactive carrier (IC) and hepatitis B envelope antigen (HBeAg)-negative hepatitis (ENEG). Aim To investigate the immune status of natural killer (NK) and T cells in different phases of chronic hepatitis B. Methods The frequency, phenotype and function of circulating NK cells, as well as nonantigen-specific and hepatitis B virus (HBV)-specific T cell responses were detected by flow cytometry in healthy and HBV-infected subjects. Results The ability of NK cells to produce IFN-γ was markedly attenuated in HBV-infected patients overall but was less compromised in IC patients. Patients in the IT and IA phases also displayed significantly lower TNF-α production compared to healthy subjects. NK cells were phenotypically activated in the IA and ENEG phases, as evidenced by the upregulation of NKp44 in CD56bright NK cells and CD69 in CD56dim NK cells. Furthermore, global T-cells from the ENEG phase displayed a proinflammatory cytokine profile with upregulated IFN-γ and TNF-α expression, while this profile was suppressed in IT and IA patients. Finally, core and S antigen-specific T cell responses were significantly stronger after in vitro expansion in the IC phase compared to other phases. Conclusion Our findings demonstrate the changes in immune response pattern during the natural history of HBV infection. Both NK and T cells are functionally impaired in the IT and IA phases. With the spontaneous clearance of HBeAg and hepatitis B surface antigen decline, NK cell cytokine production and HBV-specific T responses are partially restored in IC phase, and the ENEG phase is dominated by nonantigen-specific T cell responses.

Summary Background During the natural hepatitis B virus (HBV) infection process, some infected subjects are characterized by a sustained low serum HBV surface antigen (HBsAg) expression level. Most members in this population are chronic asymptomatic HBV carriers (ASCs). To elucidate the mechanism underlying low-level HBsAg expression in ASCs, we sequenced the HBV S gene in these patients to reveal specific sequence characteristics. Methods Overall, 1308 cases of chronic ASCs were grouped according to their HBsAg serum expression levels (10 IU/mL). The clinical characteristics of the population were analysed in detail. The HBV S gene was sequenced from 276 ASC cases with low-level HBsAg expression. Additionally, 100 of 1032 ASC cases with high-level HBsAg expression were randomly selected for HBV S gene sequencing based on age matching according to the low-level HBsAg group. A comparative analysis was conducted with the HBV S gene sequences from ASCs with low HBsAg expression and the HBV reference S gene sequences from ASCs with high HBsAg expression. Results The population with low-level HBsAg expression displayed the following primary clinical characteristics: mostly chronic asymptomatic HBV carriers, older age (mean age 55.09 years), HBsAg/anti-HBe/anti-HBc (core) positivity as the main serological pattern (97.1%), low HBV DNA replication (1.32 ± 1.60 log10 IU/mL), a low HBV-DNA positive rate (45.65%) and primarily genotype B (82.54%) and serotype adw (84.13%). The comparative analysis of the HBV S gene sequences from ASCs with low-level HBsAg showed significant mutations (including co-mutations) on both sides of the main hydrophilic region (MHR). Conclusion Significant mutations in multiple regions and at multiple sites (including co-mutations) on both sides of the MHR may be one cause of the low HBsAg expression level in this population.

Hepatitis B virus (HBV) infection is a global health problem with different immunological phases and therapeutic approaches. The serological condition of inactive carrier (IC) was recently well defined as a clinical and virological stable status, in which specific treatment is usually deferred, while the active chronic hepatitis B (CHB) condition requires an immediate treatment strategy. Recently, a possible broad antiviral effect of oxysterols, in particular 25-hydroxycholesterol (25OHC) and 27-hydroxycholesterol (27OHC), was observed, as most likely linked to the positive modulation of innate immunity, but no clear evidence is available about their possible role in chronic HBV infection. Thus, we examined the relationship between the plasma levels of oxysterols and the disease condition of 40 HBV patients, without treatment at the start of the study. Of these, 33 were ICs and 7 were active CHB subjects. A marked reduction of 25OHC and 27OHC plasma levels was detectable in all active CHB recruited patients, while the plasma values observed in ICs all remained within the physiological range. No difference was observed between the two groups of patients with regard to the plasma levels of 24-hydroxycholesterol (24OHC). Further, the plasma level of 27OHC ≥ 140 μg/L was shown to be predictive of an inactive carrier status. This cohort study points to 27OHC as a good candidate biomarker to differentiate active and inactive CHB status. An increasing bulk of research reports is supporting the very likely contribution of this oxysterol to the immunological control of chronic hepatitis B.

The natural course of chronic hepatitis B virus (HBV) infections follows distinct clinical disease phases, characterized by fluctuating levels of serum HBV DNA and ALT. The immune cells and their features that govern these clinical disease transitions remain unknown. In the current study, we performed RNA sequencing on purified B cells from blood (n = 42) and liver (n = 10) of healthy controls and chronic HBV patients. We found distinct gene expression profiles between healthy controls and chronic HBV patients, as evidenced by 190 differentially expressed genes (DEG), but also between the clinical phenotypes of a chronic HBV infection (17–110 DEG between each phase). Numerous immune pathways, including the B cell receptor pathway were upregulated in liver B cells when compared to peripheral B cells. Further investigation of the detected DEG suggested an activation of B cells during HBeAg seroconversion and an active regulation of B cell signalling in the liver.

High antigen burden during chronic hepatitis B (CHB) results in a low frequency HBV-specific T cell response with restricted functionality. However, this observation is based on limited data because low T cell frequencies have hindered effective ex vivo analysis. We adapted the ELISpot assay to overcome this obstacle to measure ex vivo T cell responses in CHB patients. We modified the key variables of cell number and the peptide pulsing method to improve ex vivo detection of HBV-specific T cells. We detected IFN-γ responses in 10/15 vaccinated controls and 20/30 CHB patients, averaging 195 and 84 SFUs/2 × 106 PBMCs respectively. Multi-analyte FluoroSpots improved functional characterization of T cells. We detected IFN-γ responses in all tested vaccinated controls (n = 10) and CHB patients (n = 13). IL-2 responses were detectable in 9/10 controls and 10/13 patients. TNF-α displayed less sensitivity, detectable in only 7/10 controls and 7/13 patients. Antigen-specific analysis demonstrated that IFN-γ responses were dominated by polymerase and core, with weak responses to envelope and X. IL-2 responses were found in 3/5 patients and equally directed towards polymerase and core. While their ex vivo frequency is extremely low, a fraction of HBV-specific T cells are detectable and display multi-functionality ex vivo.

WOS: 000433285000006, PubMed ID: 29669510, Long non-coding RNAs (lncRNAs) have been implicated in numerous biological processes, including epigenetic regulation, cell-cycle control, and transcriptional/translational regulation of gene expression. Differential expression of lncRNAs and disruption of the regulatory processes are recognized as critical steps in cancer development. The role of lncRNAs in hepatitis B virus (HBV) infection is not well understood. Here we analyzed the expression of 135 lncRNAs in plasma samples of 82 HBV patients (classified as chronic patients, inactive carriers, or resolved patients) at diagnosis and at 12 months of treatment in relation to control group (81 healthy volunteers). We also investigated the effect of small interfering RNA (siRNA)-mediated silencing of lincRNA-SFMBT2 on HBV-positive human liver cancer cell line. lncRNA expression was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Chemically synthesized siRNAs were transfected into the cell lines using Lipofectamine 2000 Reagent (Thermo Fisher Scientific). HBV DNA and HBsAg and HBeAg were detected in transfected cultures by real-time PCR and ELISA, respectively, using commercial kits. We observed changes in lncRNA expression in all three HBV groups, compared to control group. Most notably, the expression of anti-NOS2A, lincRNA-SFMBT2, and Zfhx2as was significantly increased and expression of Y5 lncRNA was decreased in chronic HBV patients. A decreased Y5 expression and increased lincRNA-SFMBT2 expression were observed in inactive HBsAg carriers. The expression of HOTTIP, MEG9, and PCAT-32 was increased in resolved HBV patients, and no significant change in the expression of Y5 was observed, compared to control group. siRNA-mediated inhibition of lincRNA-SFMBT2 decreased the level of HBV DNA in human liver cancer cells. Further research is needed to confirm the prognostic as well as therapeutic role of these lncRNAs in HBV patients., TUBITAK (the Scientific and Technological Research Council of Turkey) grantTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [215S225], This work was supported by TUBITAK (the Scientific and Technological Research Council of Turkey) grant (Project No: 215S225).

BACKGROUND The aim of this study was to characterize the expression and secretion of hepatitis B surface-antigen (HBsAg) in the hepatocytes of hepatitis B virus (HBV)-infected patients at different phases of infection; as such, the association of intrahepatic HBsAg expression with virological markers and the histological characteristics were analyzed. MATERIAL AND METHODS 302 chronic HBV infection patients who had not received antiviral therapy were stratified by HBeAg status. The proportion of HBsAg-positive cells was used as an indicator for HBsAg expression level. RESULTS In HBeAg-positive patients, there was a significant correlation between serum HBsAg and serum HBV DNA levels (r=0.569, p

As a member of the liver tropic virus family, hepatitis B virus (HBV) was thought to only infect and replicate within the liver. Sodium taurocholate co‑transporting polypeptide (NTCP) has been identified as a functional cellular receptor and a major determinant of liver tropism and HBV entry level species specificity. In the present study, the Oncomine database was used to explore differences in NTCP expression among cancerous and normal tissues. The results revealed that NTCP was highly expressed in breast cancer (BC), which was subsequently verified in clinical samples. Furthermore, in the BC tissue of patients with chronic HBV, HBV antigens, viral DNA/RNA and specific viral particles were detected via immunohistochemistry, ELISA, western blotting, reverse transcription‑quantitative PCR and electron microscopy. Different HBV biomarkers and Dane particles were detected in BC. Furthermore, high levels of HBV‑specific RNAs, the characteristic signals of HBV replication, were also detected, indicating that HBV infects BC tissue by binding to NTCP and replicating within. Based on the data of the present study, BC tissue may represent a second location of HBV infection and replication in addition to the liver.

BACKGROUND We investigated the relationship between hepatitis B virus (HBV)-related pathogenesis and single nucleotide polymorphisms (SNPs) in interleukin-21 (IL-21)-JAK-STAT signaling pathway genes. METHODS We used the high-resolution melting (HRM) method to genotype five SNPs (IL-21 rs2221903, IL-21 rs4833837, IL-21 receptor (IL-21R) rs2285452, JAK3 rs3008, and STAT3 rs1053023) in 546 HBV-infected patients and 353 healthy Chinese subjects. The HBV-infected patients were further divided into subgroups based on the HBV-related pathologies: chronic hepatitis B (CHB), HBV-related liver cirrhosis (LC), and HBV-related hepatocellular carcinoma (HCC). RESULTS There were no significant differences in the genotype and allele distributions of the five SNPs between the HBV-infected patients and healthy subjects. The genotype and allele frequencies were similar in the two groups for IL-21 rs2221903 (A>G, P = 0.83 and 0.67), rs4833837 (A>G, P = 0.80 and 0.49), IL-21R rs2285452 (G>A, P = 0.25 and 0.68), STAT3 rs1053023 (A>G, P = 1.00 and 0.96), and JAK3 rs3008 (C>T, P = 0.32 and 0.54). However, patients with the IL-21R rs2285452 AA genotype were more susceptible to HBV-related HCC than those with the IL-21R rs2285452 GA/GG genotype (P = 0.03, OR = 3.27, 95% CI = 1.16-9.20). The serological marker model of "HBsAg+, HBeAg+, HBcAb+" was predominant among patients with HBV infection. However, there was no association between the genotype's distribution of the five SNPs and the serological marker models (P > 0.05). CONCLUSIONS These findings demonstrate that the IL-21R rs2285452 AA genotype increases the risk of HBV-related HCC in Chinese patients.

The aim of this study was to determine the seroprevalence of HIV, the hepatitis B and C viruses, and syphilis as well the risk factors for these diseases among blood donors in Bangui, Central Africa Republic. This cross-sectional study examined samples from donors giving blood in August and September, 2013. HIV1/2 antibodies was screened with the Determine and Unigold HIV tests. Hepatitis B surface antigens were detected by sandwich immunochromatographic methods (DIAspot HBsAg test), and antibodies to HCV by the DIAspot test strip. Syphilis was diagnosed with the VDRL and TPHA methods (Omega Diagnostic, UK). The Chi(2) test was used for statistical analysis. The study included samples from 551 individuals, 350 (63.52%) of whom were frequent volunteer donors. In all, 132 (23.95%) were infected with at least one pathogen. The overall seroprevalence rate was 8.89% for HBV, 4.72% for HCV, 4.36% for syphilis, and 5.98% for HIV. Eight patients had two concomitant infections, with HIV-HBV the most common combination. Compared to long-term volunteers, first-time donors were more often infected by at least one of the pathogens we screened for, most especially HVB (OR = 5.06; 95% CI = 4.22-7.11) and syphilis (OR = 2.05; 95% CI = 2.02-7.44). Our findings indicate the high seroprevalence of transfusion-transmitted infections in blood donated in Bangui. The most common combined infections were HIV-HBV. The most common risk factor was a family history of HBV infection, and especially, mother-child transmission.

Background: China has been one of the countries with high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) liver disease. And lichen planus is an extrahepatic manifestation of patients with chronic HCV infection. This case-control study was conducted to investigate the relationship between oral lichen planus (OLP) and HBV/HCV infection in China. Material and Methods: A total of 776 patients, including 150 patients with OLP (Group OLP), 429 inpatients from the Trauma Ward of Oral and Maxillofacial Surgery Department (Group A), 110 patients with other oral mucosal diseases, but without a reported association with HCV infection (Group B) and 87 patients with oral lichenoid lesion (Group OLL), were compared with their seroprevalence of anti-HCV antibody (HCVAb), hepatitis B surface antigen (HBsAg) and the parameters of liver functions. Moreover, the clinical characteristics of OLP were also observed, such as gender, age, chief complaint, course of the disease, clinical type, sites involved and so on. Results: The positive rates of HCVAb and HBsAg in OLP patients were 0.7% and 4%, respectively. Neither HCVAb nor HBsAg was associated with OLP as demonstrated by both the univariate and the multivariate analyses. The clinical features and liver functions of OLP patients with negative or positive HBsAg were nearly the same. Conclusions: Our findings verify that there is no association between OLP and hepatitis and there is no need to run a screening test for HCV or HBV in OLP patients in China

Hepatitis B virus (HBV) infection is a serious nosocomial infection that affects patients undergoing hemodialysis (HD). However, certain HBV variants are not detected by routine serological tests in Egyptian dialysis units because of mutations that change important viral antigens (Ags). Of note, these mutations can result in the appearance of different HBV variants with different clinical manifestations. Thus, the present study aimed to assess different clinical forms of HBV infections and viral genotypes among patients undergoing HD in the Ismailia governorate of Egypt. To this end, serum samples were collected from 150 patients undergoing HD and screened for HBV-DNA using a nested PCR technique. Positive samples were then screened for HBV serological markers (hepatitis B core antibody [HBcAb], hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B e antigen and hepatitis B e antibody) using ELISA and the HBV viral load quantitated by qPCR. HBV genotypes were detected by direct sequencing of the partial surface (S) gene. The most common clinical form of HBV infection in our study cohort was overt HBV infection (10%); followed by seropositive occult hepatitis B infection (7.3%), most of whom had an isolated HBcAb. The least common form was the precore mutant (1.3%). All HBV isolates were genotype D. This study reveals the importance of HBcAb and PCR in screening for HBV, especially for detection of occult hepatitis B infection.

Patients with acute hepatitis B (AHB) usually present after developing symptoms; therefore, the temporal kinetics of viral markers during the incubation period have not been documented clearly. We describe an AHB infection before the onset of hepatitis, throughout the course of the disease and without anti-viral therapy. The patient initially visited our hospital for immunization against HBV and was found to be positive for viral markers: 0.0 IU/mL of anti-HBs, 0.06 S/CO of anti-HBc and 2.93 IU/mL of HBsAg. During the 14 days after his first visit, HBsAg, HBV DNA, HBe antigen and HBV core-related antigen, but not anti-HBc or anti-HBs, levels increased. On day 22, he developed acute hepatitis. The period of logarithmic viral replication was estimated to be 7.0 days. HBV genomic sequencing and phylogenetic analysis indicated transmission from the patient’s wife. Although sexual intercourse could not be ruled, another possible route of transmission was the unusual occurrence of kissing his wife when she had macroscopic bleeding after tooth brushing, 2 months before his positive HBsAg result; the day of the episode being consistent with the calculated HBV replication velocity. This study reveals the temporal kinetics of viral markers during the incubation period of AHB.

Background Previous studies have revealed that hepatitis B virus (HBV) infection may be related to rheumatoid arthritis (RA), but there are no studies on the presence of HBV antigens or nucleic acid in synovium from patients with RA with HBV infection. In the present study, we investigated the presence of HBV in the synovium and its clinical significance in RA. Methods Fifty-seven consecutive patients with active RA (Disease Activity Score 28-joint assessment based on C-reactive protein ≥ 2.6) and available synovial tissue who had completed 1 year of follow-up were recruited from a prospective cohort. The patients were divided into chronic HBV infection (CHB, n = 11) and non-CHB groups according to baseline HBV infection status. Clinical data were collected at baseline and at 1-, 3-, 6-, and 12-month follow-up. Radiographic changes of hand/wrist at baseline and month 12 were assessed with the Sharp/van der Heijde-modified Sharp score (mTSS). HBV in synovium was determined by immunohistochemical staining for hepatitis B virus surface antigen and hepatitis B virus core antigen (HBcAg) and by nested PCR for the HBV S gene. Results HBcAg was found in the synovium of patients with RA with CHB (7 of 11, 64%), which was confirmed by PCR for the HBV S gene. Compared with the non-CHB group, more CD68-positive macrophages, CD20-positive B cells, and CD15-positive neutrophils infiltrated the synovium in the CHB group (all p

To evaluate the detection rate of markers for hepatitis B virus (HBV) in the blood samples taken from patients with blood system diseases, by applying the current approaches to examining donated blood and its components for markers of viral infections.The investigation included blood samples from patients with blood system diseases (n=364) and donors (n=5,011). The results of laboratory screening of donated blood samples (n=13,081) were retrospectively analyzed. Commercial kits of reagents were used for immunochemical assay and polymerase chain reaction.Patients with blood system diseases were recorded to have markers of active HBV infection in 12.6% of cases, anti-HBc in 31.3%, and anti-HBs in 37.6%. A retrospective analysis of the results of screening donated blood samples showed the presence of markers for active HBV infection in 0.28% of cases. A prospective examination of blood donors revealed markers of HBV infection in 4.83% of cases, including those of active forms in 0.54% and anti-HBc in 4.79%. The markers of active HBV infection in donors were only anti-HBc IgM in 0.42% of cases. The blood samples from donors with an anti-HBs titer of200 mIU/ml contained anti-HBc IgM in 10.5%.In the last 5-7 years, the detection rate of markers of HBV infection in the blood samples of patients with blood system diseases have remained at a high level. Screening for decreed markers fails to identify people with inapparent infections among the donors. Even high anti-HBs concentrations in the donated blood may be a risk for HBV transmission by transfusion to a recipient.Цель исследования. Оценка частоты выявления маркеров вируса гепатита В (HBV) в образцах крови больных с заболеваниями системы крови с использованием современных подходов к обследованию доноров крови и ее компонентов на маркеры вирусных инфекций. Материалы и методы. В исследование включили образцы крови пациентов с заболеваниями системы крови (n=364) и доноров (n=5011). Ретроспективно проанализированы результаты лабораторного скрининга образцов крови доноров (n=13 081). Для проведения иммунохимического анализа и полимеразной цепной реакции использовали коммерческие наборы реагентов. Результаты. Маркеры активной инфекции HBV у больных с заболеваниями системы крови зарегистрированы в 12,6% случаев, анти-HBc - 31,3%, анти-НВs - 37,6%. Ретроспективный анализ результатов скрининга образцов крови доноров показал наличие маркеров активной инфекции HBV в 0,28% случаев. В проспективном обследовании доноров крови у 4,83% выявлены маркеры инфекции HBV, в том числе активной формы 0,54%, анти-HBc 4,79%. В 0,42% случаев маркерами активной инфекции HBV у доноров были только aнти-HBc-IgM. Образцы крови доноров с aнти-HBs в титре200 мМЕ/мл в 10,5% содержали aнти-HBc-IgM. Заключение. В последние 5-7 лет частота обнаружения маркеров инфекции HBV в образцах крови пациентов с заболеваниями системы крови сохраняется на высоком уровне. Скрининг на декретированные маркеры не позволяет выявлять скрыто инфицированных лиц среди доноров. Даже при высокой концентрации aнти-HBs в крови донора существует риск потенциальной трансфузионной передачи HBV реципиенту.

Hepatitis B virus infection (HBV) is a significant public health problem in sub-Saharan Africa. Universal infant vaccination with the hepatitis B (HB) vaccine has been implemented within the South African Expanded Programme of Immunization since April 1995 with concomitant reduction in HBV infection in children. However, the first vaccine dose is only administered at six weeks of age. This delay may lead to a failure to reduce the risk of perinatal HBV transmission to infants born to HIV/HBV co-infected women, in whom HBV infection is often upregulated. The aim of this study was to determine the prevalence of HBV infection in babies born to HIV-infected mothers in the Western Cape, South Africa. HBV serological markers were tested in all infant serum samples and following HB viral load testing, sequencing and genotyping were also performed. Three of 1000 samples screened tested positive for HBsAg and HBV DNA. An additional infant tested positive for HBV DNA alone. All babies had received the HB vaccine at 6, 10 and 14 weeks. The prevalence of HBV infection was therefore 4/1000 (0.4%; 95% CI, 0.01–0.79%). Three of four infants and all four mothers were followed-up. Two infants were persistently positive for HBsAg with viral loads above 108 International Units per millilitre. All four maternal samples were positive for HBsAg and HBeAg and one was also positive for anti-HBe. Sequencing analysis of two mother–child HBV pairs showed 100% sequence identity. This study demonstrates HBV infection in HIV-exposed infants despite HB vaccination from 6 weeks of age. A more strategic approach is needed to prevent mother to child transmission of HBV, including screening of pregnant women, HBV-targeted antiviral therapy and HB birth dose vaccine.

BACKGROUND Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is a rare subtype of primary liver cancer consisting of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Because of the rarity of this tumor, its feature is poorly understood. The present study aimed to evaluate the clinicopathological features and long-term prognosis of patients with cHCC-CC after surgery and to compare with those of the patients with stage-matched HCC and CC. METHODS The clinicopathological features of the patients who underwent surgery for cHCC-CC at our center during the period of 2001-2010 were retrospectively analyzed and compared with those of stage-matched HCC and CC patients. Cancer staging was performed according to the AJCC Cancer Staging Manual (6th ed.). Overall survival and disease-free survival were compared among the groups and prognostic factors of cHCC-CC were evaluated. RESULTS Significant differences were observed in clinicopathological features among 42 patients with cHCC-CC, 90 patients with HCC and 45 patients with CC. Similar to HCC patients, cHCC-CC patients had frequent hepatitis B virus antigen positivity, microscopic vessel invasion, cirrhosis and high level of serum alpha-fetoprotein. Similar to CC patients, cHCC-CC patients showed increased bile duct invasion and decreased capsule. The 1-, 3-, and 5-year overall survival and disease-free survival of patients with cHCC-CC were not significantly different from those with stage-matched patients with CC; but significantly poorer than those with HCC. In subanalysis of patients with stage II, the overall survival in patients with cHCC-CC or CC was significantly poorer than that in patients with HCC. We did not find the difference in patients with other stages. Univariate analysis of overall and disease-free survival of patients with cHCC-CC showed that the vascular invasion and intrahepatic metastasis were the significant predictive factors. CONCLUSION Patients with cHCC-CC showed similar clinicopathological features as those with HCC or CC, and patients with cHCC-CC or CC had a poorer prognosis compared with those with HCC, especially at matched stage II. (Hepatobiliary Pancreat Dis Int 2014;13:594-601)

Chronic hepatitis B (CHB) has become a treatable and controllable disease. The current nucleos(t)ide analogue (NUC) and pegylated interferon therapies effectively help slow disease progression and reduce the risk of cirrhosis, hepatocellular carcinoma (HCC), and CHB-associated mortality. Long-term viral suppression is easily achievable by NUC therapy, with limited adverse reactions. However, several unmet requirements still exist, including safety and risk-stratified HCC surveillance among patients who received long-term NUC therapy. Criteria for determining which patients should receive finite-duration NUC therapy and which should receive combination therapy with both NUC and pegylated interferon remain unsettled. The management of hepatitis B virus (HBV) e antigen-positive viremic patients with normal liver function and the incorporation of new biomarkers to help manage CHB require further exploration. To achieve functional cure (ie, HBV surface antigen seroclearance) and complete cure (ie, eradication of covalently closed circular DNA) of CHB, several challenges in basic research must be addressed, including the development of an efficient cell culture system and animal models for HBV investigation, development of treatment to eradicate covalently closed circular HBV DNA, and development of immunotherapy for CHB. This brief review focuses on unmet needs in both clinical and basic HBV research.

Introduction: Diagnosis of chronic hepatitis B virus (HBV) infection particularly its occult form requires monitoring and repeat serological and molecular studies. The aim of the study was to investigate the possible relation between the case of a family outbreak of hepatitis A and the finding that a member of this family was diagnosed with chronic hepatitis B. Methodology: A mother and her two sons, one previously diagnosed with chronic HBV infection, were hospitalized due to suspected acute hepatitis. Serological markers for hepatitis A, hepatitis B and hepatitis C were assessed. Additionally, HBV DNA was tested with a sensitive PCR. Hepatitis B vaccine was administered to the mother to differentiate resolved from occult HBV infection. Results: A family outbreak of hepatitis A was confirmed, alongside a focus of chronic HBV infection. The serological profile for two brothers was HBsAg(+), anti-HBcIgM(-), anti-HBc(+), HBcAg(-)/anti-HBe(+). The mother was negative for all HBV markers except anti-HBc. HBV DNA was detected at a level of 461 IU/mL in the elder brother, 3647 IU/mL in the younger brother and was negative in the mother on two occasions. Her anti-HBc alone, having two sons with chronic HBV infection, and her lack of antibody response to hepatitis B vaccine despite being negative for HBV DNA, led to the diagnosis of probable occult HBV infection. Conclusion: Our results confirmed that a vaccination approach could facilitate diagnosis of chronic HBV infection in the presence of isolated anti-HBc. If it were not for a family outbreak of hepatitis A, this unexpected family HBV focus would not have been revealed.

Entecavir 0.5 mg (ETV) is widely used among treatment-naive chronic hepatitis B (CHB) patients. However, 10%-30% of patients show partial virologic response (PVR) to the drug. If the hepatitis B virus (HBV) continues to replicate, the underlying liver disease may progress. Herein, we compared the efficacy of switching to tenofovir disoproxil fumarate (TDF) with that of continuing ETV in CHB patients with PVR to ETV. This was an open-label randomized controlled trial including CHB patients who had been receiving 0.5 mg of ETV for >12 months, but who still had detectable HBV DNA levels of >60 IU/mL without known resistance to ETV. Sixty patients were enrolled and 45 qualified for the study: Twenty-two patients were randomly assigned into the TDF group and 23 into the ETV group. After 12 months of treatment, the virologic response rate (HBV DNA

In 70 chronic hepatitis B patients with hepatitis B surface antigen seroclearance during nucleos(t)ide analogue therapy, response was sustained in all 54 patients who discontinued treatment. Clinically significant relapses as indicated by high hepatitis B virus DNA and ALT levels were not observed. Anti-HBs positivity may not be required to ensure sustained off-treatment response.

OBJECTIVE: In Denmark, pregnant women have been screened for hepatitis B virus (HBV) since 2005, and children born to HBV-infected mothers offered hepatitis B immunoglobulin at birth, vaccination against HBV at birth and after 1, 2 and 12 months. The purpose of this study was to determine the risk of vertical HBV transmission in children born to mothers with chronic HBV infection, to investigate the antibody response in the children and to investigate possible maternal predictive risk factors for HBV transmission.MATERIALS AND METHODS: Through the Danish Database for Hepatitis B and C, we identified 589 HBV-infected women who had given birth to 686 children, of whom 370 children were born to 322 women referred to hospital. 132 (36%) children, born to 109 mothers, were included in the study; 128 children had blood samples tested for HBsAg, anti-HBc (total), anti-HBs and HBV-DNA and four children had saliva samples tested for anti-HBc.RESULTS: We found vertical HBV transmission in Denmark to be 2.3% [95% CI: 0.5, 6.5], a high proportion of HBsAg-negative children with low levels of anti-HBs (18.4%) and a high proportion (15.2%) with resolved HBV infection. No maternal risk factor was statistically significantly associated with HBV vertical transmission.CONCLUSION: In a HBV low prevalence setting as Denmark, despite a national vaccination program, vertical HBV transmission occurred in 2.3% of children born to HBV-infected mothers. In addition, a high proportion of the children had insufficient anti-HBs levels and a high proportion had serological signs of resolved HBV infection.

Summary Given the importance of the control of sexually transmitted infections in the general population and specifically in the prison system, we rolled out this cross-sectional study in 2007. Standard questionnaires and blood samples were accessed among 680 prisoners. The protocol was approved by the Ethics Committee. We determined the following seroprevalences: HIV, 1.8% (95%CI = 0.1–3.3); HBV, 21.0% (95%CI = 17.8–25.1); HBV, 5.3% (95%CI = 3.5–7.6) and syphilis 5.3% (95%CI = 3.5–7.6). Logistic regression identified significant associations with ( p

AIM To investigate whether hepatitis viral DNA load at 24 wk of treatment predicts response at 96 wk in patients with chronic hepatitis B. METHODS A total of 172 hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B patients who received initial treatment at 16 tertiary hospitals in Hunan Province, China were enrolled in this study. All patients received conventional doses of lamivudine and adefovir dipivoxil, telbivudine, entecavir dispersible tablets, or entecavir tablets for 96 wk. Patients who used other antiviral drugs or antitumor and immune regulation therapy were excluded. Patients were stratified into three groups according to their viral DNA load at 24 wk: < 10 IU/mL (group 1), 10-103 IU/mL (group 2), and > 103 IU/mL (group 3). Correlations of 24-wk DNA load with HBeAg negative status and HBeAg seroconversion at 96 wk were analyzed. Receiver operating characteristic curve analysis was used to test the predictive value of the HBV DNA load at 24 wk for long-term response. RESULTS The rates of conversion to HBeAg negative status and HBeAg seroconversion rates were 53.7% and 51.9%, respectively, in group 1; 35.21% and 32.39% in group 2; and 6.38% and 6.38% in group 3. The receiver operating characteristic curves for the three subgroups revealed that the lowest DNA load (< 10 IU/mL) was better correlated with response at 96 wk than a higher DNA load (10-103 IU/mL). Nested PCR was used for amplifying and sequencing viral DNA in patients with a viral DNA load > 200 IU/mL at 96 wk; resistance mutations involving different loci were present in 26 patients, and three of these patients had a viral DNA load 10-103 IU/mL at 96 wk. CONCLUSION Hepatitis B viral DNA load at 24 wk of antiviral treatment in patients with chronic hepatitis B is a predictor of the viral load and response rate at 96 wk.

Hepatitis B virus (HBV) infection can lead to different types of chronic kidney diseases (CKD) in clinical practice. However, HBV infection has been observed to have no significant association with CKD indicators in some epidemiological surveys. This research aims to estimate CKD prevalence in HBV infection population and clarify the relationship between HBV infection status and CKD. The participants aged 20 to 49 years were selected by multistage random sampling from January 1, 2010 to December 31, 2012 across 31 provinces and regions in rural China. The data was collected by standard questionnaire and physical check-up. Status of HBV infection was diagnosed as immune tolerant phase, hepatitis B envelope antigen -positive chronic HBV infection, inactive HBV carrier, hepatitis B envelope antigen -negative chronic HBV infection and resolved HBV infection based on serological markers, and the level of hepatic function, respectively. In total, 2,969,502 subjects were included in the study. In population aged 20 to 49 years in rural China, prevalence of HBV infection was 12.17%. Prevalence of proteinuria, hematuria, estimated glomerular filtration rate less than 60 mL/min/1.73m2 and CKD was 0.94%(95% CI = 0.91–0.97%) vs. 0.65%(95% CI = 0.64–0.66%), 1.92%(95% CI = 1.87–1.96%) vs. 1.19% (95% CI = 1.18–1.21%), 1.02%(95% CI = 0.99–1.06%) vs. 0.77% (95% CI = 0.76–0.78%), and 3.85%(95% CI = 3.78–3.91%) vs. 2.60%(95% CI = 2.58–2.62%) in population with HBV infection and without infection, respectively. Prevalence of CKD and indicators was higher in population in every status of HBV infection than in population without infection, respectively (all P

Background & objectives: This study was undertaken to evaluate a community based programme of antenatal screening for hepatitis B surface antigen (HBsAg) and selective immunization of children commencing at birth, at a secondary care hospital in south India. The primary objective was to assess immunization coverage among children born to HBsAg positive women; secondary objectives were to study the prevalence of HBsAg among antenatal women, prevalence of HBsAg among immunized children (to estimate vaccine efficacy), seroconversion rate and relationship of maternal hepatitis B e antigen (HBeAg) to hepatitis infection. Methods: The prevalence of hepatitis B antigen among antenatal women and immunization coverage achieved with hepatitis B vaccine in a rural block in Vellore, Tamil Nadu were assessed through examination of records. Children born between May 2002 and December 2007 to hepatitis B positive women were followed up for a serological evaluation, based on which vaccine efficacy and the effect of maternal hepatitis B e antigen (HBeAg) on breakthrough infection was estimated. Results: The prevalence of hepatitis B surface antigen among antenatal women was 1.58 % (95% CI: 1.35-1.81%). Vaccine coverage for three doses as per a recommended schedule (including a birth dose) was 70 per cent, while 82.4 per cent eventually received three doses (including a birth dose). Estimated vaccine efficacy was 68 per cent and seroconversion 92.4 per cent in children aged 6-24 months. Maternal HBeAg was significantly associated with either anti-HBc or HBsAg in immunized children, RR=5.89 (95% CI: 1.21-28.52%). Interpretation & conclusions: The prevalence of hepatitis B among antenatal women in this region was low and a programme of selective immunization was found to be feasible, achieving a high coverage for three doses of the vaccine including a birth dose.

We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation.

BACKGROUND: The course of hepatitis B virus (HBV) infection does not appear to be determined by variations in viral virulence and may be influenced by the host immune response. We studied the distribution of human leukocyte antigens in children and adult men in the Gambia who spontaneously recovered from HBV infection as compared with the distribution of these antigens in subjects with persistent infection. METHODS: In a two-stage, case-control study, we analyzed the frequency of MHC class I antigens and class II haplotypes in people with either transient or persistent HBV infection. MHC class I typing was performed by microlymphocytotoxicity assays. MHC class II typing was performed with analysis of restriction-fragment-length polymorphisms (RFLPs), supplemented by other techniques. RESULTS: In the first stage (the study of children up to the age of 10 years), the RFLP pattern 25-1, which includes the class II allele HLA-DRB1*1302, was found in 58 of 218 subjects with transient HBV infection (26.6 percent) and 30 of 185 subjects with persistent infection (16.2 percent) (relative risk of carrying the 25-1 pattern in the persistently infected group as compared with the transiently infected group, 0.53; 95 percent confidence interval, 0.32 to 0.90; P = 0.012). In the second stage (the study of adults), HLA-DRB1*1302 was found in 50 of 195 subjects with transient HBV infection (25.6 percent) and in 3 of 40 subjects with persistent infection (7.5 percent) (relative risk, 0.24; 95 percent confidence interval, 0.04 to 0.80; P = 0.012). The RFLP pattern 13-2, which includes the class II allele DRB1*1301, was less frequent in children with persistent infection than in those with transient infection, an association that was neither confirmed nor excluded by the data on adults. Possible associations with HLA class I antigens found in children were not supported by the data on adults. CONCLUSIONS: The MHC class II allele DRB1*1302 was associated with protection against persistent HBV infection among both children and adults in the Gambia.

Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%-2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%-3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%-7.8%). Sixty-one (8.0%; 95% CI, 6.2%-10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB.

OBJECTIVE: The aim of the present study was to determine the genotype association for alleles of class II human leukocyte antigens (HLA) in the DRB1* locus among blood donors at the Fundacao Hemope (Brazil) infected by or immunized for the hepatitis B virus (HBV). METHODS: A case-control study was performed, comprising a group of individuals infected by HBV and a control group of immunized individuals at a proportion of 1:4. Blood samples were taken for the HLA typing of the DRB1* locus. Univariate and multivariate analyses were performed for the assessment of associations between the categorical variables using the chi-squared test and Fisher's exact test. RESULTS: A total of 320 blood donors were analyzed (241 males [75%] and 79 females [25%] with a mean age of 39 years). The case group consisted of 64 HBV-infected donors and the control group was composed of 256 HBV-immunized donors. The multivariate analysis stratified by gender revealed that the DRB1*09 allele was associated with infected male donors (p = 0.016) and the DRB1*08 allele was associated with infected donors aged 39 years or younger (p = 0.031). CONCLUSION: The results of the present study reveal that younger blood donors and male blood donors who respectively exhibit the DRB1*08 and DRB1*09 alleles are more susceptible to intensification of HBV infection.

Objectives: To compare B-type natriuretic peptide (BNP) and echocardiographic parameters in patients with hepatitis B virus (HBV) and healthy control subjects. Subjects and Methods: 52 consecutive patients with HBV and 47 healthy controls were examined. All subjects underwent transthoracic echocardiography after a complete medical history and laboratory examination including BNP, C-reactive protein (CRP) and high-sensitivity CRP (hsCRP). Results: Demographic characteristics were similar in patients with HBV and the control group. No significant difference was found in conventional Doppler and tissue Doppler parameters between the two groups. BNP levels were significantly higher in patients with HBV [6.5 ng/l (range 0.5-85.2)] than controls [4.3 ng/l (range 0.5-18.3)], p = 0.039. hsCRP [3.25 mg/l (0.02-40.2) vs. 0.5 mg/l (0.02-8.0)] levels were significantly higher in patients with HBV than control subjects (p < 0.001). Conclusion: Patients with HBV had higher BNP, CRP, and hsCRP levels than controls. Echocardiographic findings were similar in both groups. This slight BNP elevation in HBV patients may be related to chronic inflammation due to HBV.

Background: Around a quarter of individuals infected with hepatitis C virus (HCV) are spontaneously able to clear the virus. Correlates of spontaneous HCV clearance are not well established and the aim of this study was to characterize factors associated with spontaneous HCV clearance in a human immunodeficiency virus (HIV)-co-infected cohort. Methods: We analyzed 327 anti-HCV-positive HIV-1-infected patients using multivariate logistic regression. HCV clearance was defined as the presence of anti-HCV with undetectable HCV RNA from at least 2 measurements more than 6 months apart. Results: We included 327 HIV-1-infected individuals, predominantly of Caucasian race; 112 (34%) were females, 258 (79%) were injecting drug users (IDU), 25 (8%) were men who have sex with men (MSM), and 20 (6%) were hepatitis B surface antigen (HBsAg)-positive. Seventy-six (23%; 95% confidence interval (CI) 18-28) had cleared their HCV infection and 251 (77%; 95% CI 72-82) had a chronic infection. The clearance rate in HBsAg-positive individuals was 65%. Being female, HBsAg-positive, or belonging to HIV exposure groups IDU and MSM predicted higher HCV clearance rates (adjusted odds ratio (aOR) 1.8, 95% CI 1-3.2; aOR 7.6, 95% CI 2.7-21; aOR 5.2, 1.2-23.5; and aOR 10.2, 95% CI 1.8-58, respectively). Race, acquired immunodeficiency syndrome (AIDS), and antiretroviral therapy were not associated with HCV clearance. Conclusions: The HCV clearance rate in this HIV-1 cohort was 23%. MSM and IDUs may have higher clearance rates due to their repeated exposure to low-dose HCV, leading to immune memory. Our data suggest an interaction of hepatitis B virus and HCV that influences the outcome of acute HCV infection.

To compare the management and the virological and serological efficacy of treatments for chronic hepatitis B (CHB) in HIV positive and negative patients.Two hundred and forty-six HIV positive and 205 HIV negative consecutive patients with past or present CHB, seen in October 2008 in participating departments, were included in a multicenter study. All the data were retrospectively collected from the first visit to October 2008 through a standardized questionnaire.Compared to HIV negative patients, HIV positive patients more often presented positive HBeAg (46.4% vs. 32.8%, p=0.01), HBV genotype A (54.8% vs. 17.1%, p0.0001), co-infection with HCV (12.4% vs. 5.9%, p=0.0002) or HDV (12.6% vs. 2.9%, p=0.04). HIV positive patients were more often on HBV therapy (92.7% vs. 57.1%, p0.0001), leading to undetectable serum HBV DNA levels (71.0% vs. 44.1%, p0.0001). In HIV positive patients, multivariate analysis showed that older age, lower initial HBV DNA levels, and longer time on HBV therapy significantly correlated with undetectable HBV DNA. No difference in efficacy was observed between tenofovir used alone or in combination. HBsAg (but not HBe) loss was more often observed in HIV positive patients, sometimes followed by HBsAg re-appearance after withdrawal of HBV treatment. Excluding the 37 HBV-HCV-co-infected patients, the last clinical presentation and liver fibrosis scores were similar in HIV positive and negative patients.The assessment of CHB and the efficacy of HBV therapy have improved in HIV positive patients. HIV infection did not have a negative impact on the likelihood of HBV therapeutic success.

Asian Americans exhibit a high prevalence of chronic hepatitis B (CHB) compared with the general population in the United States. However, there are specific barriers to appropriate health care in the Asian American population, and CHB awareness is low. The aim of this study was to examine CHB awareness among the Asian American population and to assess the role and attitudes of primary care physicians in CHB diagnosis and treatment, particularly in relation to Asian American communities.Participants from the Asian American community were randomly selected using telephone directories, and completed a questionnaire regarding attitudes toward CHB during telephone interviews. Primary care physicians completed a structured, online questionnaire.A total of 610 Asian Americans (Chinese, Korean, and Vietnamese communities) and 393 physicians participated in the study. There appeared to be some level of awareness of CHB and its seriousness among the Asian American participants; many respondents agreed with statements regarding the seriousness of the disease (66%) and a high proportion (71%) reported having had a blood test for hepatitis B virus (HBV). Of those who were found to be negative for HBV, only 61% reported that they had been vaccinated, and almost one-third agreed that vaccination was unnecessary (30%). Most primary care physicians perceived CHB to be an important disease (83% thought it was very or extremely serious). However, despite awareness of the high prevalence of CHB among the Asian American community, universal screening is not practiced by most physicians. Furthermore, there was low awareness of current major CHB guidelines (62% were unfamiliar with the major treatment guidelines).Improved education regarding CHB disease progression, prevention, and treatment is needed among both the Asian American community and primary care physicians to increase awareness of the seriousness of the disease and ultimately reduce the burden of CHB in the United States.

Urine was examined for the presence of hepatitis associated antigen (HAA) by means of gel diffusion and immunoelectrophoresis in thirteen renal transplant recipients who were known serum carriers of HAA. Three 24-hour urine collections were obtained from twelve of the patients and two from one. All unconcentrated urine specimens examined were HAA negative. After 500-fold concentration HAA could be demonstrated in the urinary samples obtained from four of the patients. HAA urinary excretion was not related to any of the kidney or liver parameters studied. Antigenuria could not be explained by increased glomerular permeability suggesting that HAA may propagate in the renal parenchyma and/or in the urinary tract.

Forty-two consecutive patients with biopsy verified chronic hepatitis and available serum specimens were examined for the occurrence of Australia antigen, antinuclear antibodies, smooth muscle antibodies and mitochondrial antibodies. Twelve patients with persistent Australia antigen, but without circulating autoantibodies (group 1) were compared with twenty-seven patients without Australia antigen, but with circulating autoantibodies (group 2). Young males with a history of serum hepatitis were predominant in group 1, while most of the patients in group 2 were middle-aged women with an insidious onset of the disease. The biochemical activity of the liver disease was more pronounced in group 2. It is concluded, that the histological defined chronic hepatitis may include several disease entities of which at least two can be separated by the serology. The relevance of this classification is supported by the fact, that there are more patients developing cirrhosis in group 2 than in group 1.

Smooth-muscle antibodies (SMA) of the IgG and IgM class in titres of 10 to 80 were demonstrated in 19 of 38 patients with acute hepatitis (50 per cent). No IgA-SMA were detected. IgM-SMA occurred in the beginning of the disease, while IgG-SMA were found both early and late in the course of disease. There was no correlation between the occurrence of SMA and the biochemical liver parameters or the mode of exposure to infection, but IgM-SMA were found more often in the first serum sample obtained from patients without hepatitis-B-associated antigen (HBAg) than in HBAg-positive patients (P1 + P2 = 0.04) and it is suggested that hepatitis virus A more readily than hepatitis virus B can elicit the formation of SMA. The mean PHA-induced lymphocyte-transformation response was significantly lower in hepatitis patients than in the controls (0.02 greater than p greater than 0.01). The lymphocyte-transformation response to a low PHA dose (1 mug per ml) was lower in hepatitis patients without SMA than in those with SMA (0.10 greater than p greater than 0.05). SMA were not found in 28 control persons, and the incidence of tissue antibodies other than SMA did not differ in hepatitis patients and controls.

Toxoplasma gondii infections can induce serious complications in HIV-infected pregnant women, leading to miscarriage; favour the mother-to-child transmission of HBV and HIV and birth defects. The purposes of this study were: (1) to quantify IgM and IgG antibodies to Toxoplasma gondii in HIV-seropositive and seronegative pregnant women, (2) to identify hepatitis B antigens (HBsAg) in pregnant women and (3) to determine T. gondii and HBV co-infections among these patients. The study was conducted at Centre Medical Saint Camille, in Burkina Faso from January to June 2009. A total of 276 HIV-infected and uninfected pregnant women were included. All women had less than 32 weeks of amenorrhoea and were aged from 19 to 42 years. Toxoplasma gondii antibodies and HBsAg were detected using ELISA method. In addition, women freely agreed to answer a questionnaire. The results of our investigations revealed that, among these pregnant women, 38.8% were illiterates, 50.4% were housewives and only 5.4% were civil servants. Positive T. gondii-specific IgM (4.7%) and IgG (27.2%) were detected. In this study, we found that HIV-seropositive status seem to be associated with great prevalence rates of both T. gondii (31.9 vs. 22.5%) and HBV (13.0 vs. 5.8%). The elevated co-infection rate in HIV-positive women suggested that they are exposed to T. gondii and HBV infections prevalently because of their immune depression. Therefore, to reduce the prevalence of T. gondii and HBV among HIV-seropositive pregnant women, lamivudine could be included in their HEART and women should follow healthy lifestyle formation.

The number of circulating T and B lymphocytes was estimated in 25 patients with biopsy-verified chronic non alcoholic liver disease. Fifteen of these had circulating HBSAg and/or anti-HBSAg and 10 were without these markers of HB virus infection. In both groups of patients a significant decrease of T cells and a parallel significant increase in null cells was found, but any difference with respect to T and null cells in patients in the two groups was not observed. Liver biopsies from five of the patients with and four without HBSAg and/or anti-HBSAg were studied for the presence of immunoglobulin bearing cells. In three out of five liver biopsies from the HBSAg and/or Ab positive patients and in two out of the four liver biopsies from the HBSAg and anti-HBSAg negative patients, a heavy periportal infiltration with plasma cells was found. However, the number and classes of the immunoglobulin containing cells could not be correlated either to the histological evaluation of the stage of activity of the liver disease or to the markers for HB virus infection. The immunological findings in the two groups of patients with chronic liver disease seem to be of the same nature and are most likely a consequence of the liver disease and not the cause of it.

Objectives Tenofovir disoproxil fumarate (TDF) is active against hepatitis B virus (HBV) and HIV. However, the long-term efficacy of tenofovir disoproxil fumarate (TDF) is not well known and the appearance of resistance is a major concern. We have studied the efficacy of TDF against HBV in patients treated at an Infectious Diseases Unit. Methods We carried out a retrospective observational study of the efficacy of TDF against HBV replication in a cohort of 52 HIV-coinfected patients who received TDF for at least 6 months. Results The median duration of follow-up of TDF treatment was 34 months. Forty-one patients (79%) were positive for HBV envelope antigen (HBeAg) and 35 had received previous lamivudine monotherapy for a median duration of 32 months. Virological breakthrough was observed in nine cases (17%). At the end of the follow-up period, HBV DNA levels were

T lymphocyte responses to hepatitis B virus (HBV) core antigen (HBcAg) are vigorous and easily detectable in vitro during recovery from acute hepatitis B but significantly weaker in patients with chronic HBV infection. In contrast, T cell responses to hepatitis B surface antigen (HBsAg) are almost undetectable during infection and even in a substantial fraction of subjects receiving vaccination with HBsAg. The aim of this study was to investigate whether the use of dendritic cells (DCs) in an in vitro assay could increase the detection of HBV-specific T cells in these conditions. Autologous monocyte-derived DCs, compared to direct HBsAg addition to the cultures, increased the stimulation of HBs-specific T cells. These were detected in 73% of healthy subjects who had recently received hepatitis B vaccine and in 43% of patients recovering from acute hepatitis B. Likewise, proliferation in response to DC-presented HBcAg was detected in both CD4(+) and CD8(+) T cells from the majority of chronic hepatitis B patients. A longitudinal evaluation of HBc-specific T cell responses during and after a 1-year treatment with pegylated interferon (IFN)-alpha showed that HBc-specific CD4(+) T cell responses had no correlation with sustained virus suppression whereas CD8(+) T cell responses were more frequently detected in patients able to control HBV replication after therapy interruption. The use of autologous DCs as antigen-presenting cells appears applicable to clinically relevant in vitro evaluation of T cell responses, particularly in those conditions characterized by low frequency of circulating antigen-specific cells and suboptimal in vivo activation. J. Med. Virol. 81:332-339, 2009. (c) 2008 Wiley-Liss, Inc.

Hepatitis B surface antigen (HBsAg) loss under antiviral therapy is rare in chronic hepatitis B patients and the dynamics of serum HBsAg in these patients are not available. The changes in serum HBsAg following treatment with adefovir (n=31) or peg-interferon-alpha-2a (n=23) were studied in hepatitis B e-antigen (HBeAg) positive chronic hepatitis B patients. Abbott Architect HBsAg assay was used to quantify serum HBsAg. HBsAg levels were significantly decreased during the first 12 weeks of treatment with median change of -397.0 IU/ml and -555.4 IU/ml, respectively for adefovir and peg-interferon-alpha-2a (p=0.005 and 0.001, respectively). Beyond 12 weeks, no further significant HBsAg reductions were found even in patients with sustained viral replication inhibition in either group. Three distinct patterns of HBsAg changes were observed in most patients in both treatment groups: biphasic pattern (rapid HBsAg reduction from baseline to week 12); assurgent pattern (higher HBsAg level at week 12 than at baseline); and wavy pattern (HBsAg reduction from baseline to week 12, followed by relapse at week 24 or week 28). These results might offer insights into the possible mechanism(s) underlying the unusual occurrences of HBsAg loss under antiviral therapy.

— Eight patients with chronic (mean 52 months) type B hepatitis (chronic active hepatitis and active cirrhosis) and markers of active viral replication (presence of HBeAg and HBV-DNA in serum) were treated with Ara-AMP for 7–12 weeks. The mean follow-up time was 18.3 months. All but one patient responded to treatment. In seven patients, HBeAg and HBV-DNA became negative and developed anti-HBe. One patient lost HBsAg as well as HBeAg and HBV-DNA. HBcAg in liver tissue became undetectable or greatly reduced in the seven patients in whom it was strongly positive. Aminotransferase and immunoglobulin levels reverted to normal in the seven responders and remained normal through the entire follow-up period. A second liver biopsy, performed after completion of therapy, showed improvement in six of eight cases, with disappearance of lobular activity. Two patients treated for 12 weeks developed a severe polyneuropathy lasting for 6 months. A 7-week course of Ara-AMP seems to induce long-lasting inhibition of viral replication, along with an improvement in liver function tests and liver histology, without significant side effects. On the other hand, a 12-week course was associated with the development of a severe and prolonged polyneuropathy.

IgM antibody to hepatitis B core antigen (IgM anti-HBc) may indicate an active immune response to persistent infection with hepatitis B virus (HBV). We studied 186 Greek HBsAg carriers for IgM anti-HBc and attempted to correlate it with other HBV and hepatitis delta virus (HDV) markers. Overall, IgM anti-HBc was detected more frequently than HBV DNA in this population (50% vs 34, p less than 0.001); this was also true for the 149 of the 186 HBsAg carriers with antibody to hepatitis B e antigen (anti-HBe) (48% vs 22%, p less than 0.001). The opposite was found in the carriers positive for hepatitis B e antigen (HBeAg): HBV DNA was observed in 93% and IgM anti-HBc in 64% of the cases (p less than 0.05). The detection of these markers was independent of sex. Serum alanine aminotransferase (ALT) levels were significantly more elevated in patients with positive tests for IgM anti-HBc and HBV DNA than in patients positive only for HBV DNA (p less than 0.001) irrespective of their HBeAg or anti-HBe status. Moreover, the detection of elevated ALT was independent of the intensity of the HBV DNA hybridization signal. Antibodies to hepatitis delta antigen (HDAg) were only found in 4 (2.4%) of 167 patients tested.

Background and Aim: The localization of hepatitis B virus (HBV) core antigen to the nucleus or cytoplasm of hepatocytes has biological implications for viral packaging and persistence. This study examined the relationship between the localization of hepatitis B virus antigens, histological activity, and viral titer in patients with chronic HBV infection. Methods: Liver biopsies from 110 patients with chronic HBV infection were studied. Ishak's scoring system was used for the histological analysis. The localization of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) and the percentage of hepatocytes stained positive by immunohistochemistry were correlated with viral titer, histological activity, and fibrosis indices using Spearman rank correlation. Results: In 88 hepatitis B e-antigen (HBeAg)-positive individuals, the nuclear localization of HBcAg correlated significantly with DNA titer (r = 0.435, P = 0.001) and negatively with fibrosis (r = −0.297, P = 0.005). The cytoplasmic localization correlated significantly with histological activity (r = 0.211, P = 0.049). In 22 HBeAg-negative individuals, the nuclear localization of HBcAg correlated significantly with histological activity (r = 0.625, P = 0.002), DNA titer (r = 0.651, P = 0.009), and fibrosis (r = 0.447, P = 0.042). The cytoplasmic localization correlated significantly with DNA titer (r = 0.524, P = 0.045) and fibrosis (r = 0.528, P = 0.012). There was no correlation of HBsAg expression with DNA titer, histological activity index, or fibrosis in both groups. HBeAg-positive patients presented at a younger age. Conclusion: In HBeAg-positive individuals, nuclear core antigen correlated with DNA titer, and cytoplasmic localization with histological activity, whereas in HBeAg-negative individuals, nuclear localization correlated with DNA titer, histological activity, and fibrosis, and cytoplasmic localization correlated with DNA titer and fibrosis, but not with histological activity. These observations suggest biological differences between HBeAg-positive and -negative disease.