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Abstract Background To evaluate the efficacy and safety of telbivudine in chronic hepatitis B women during the second and third trimesters of pregnancy. Methods The week 12–34 of pregnant women were screened in this prospective non-intervention study, with HBV DNA > 106 IU/mL and alanine aminotransferase > 50 IU/L. The patients were received telbivudine treatment as a treatment group or without antiviral treatment as a control group. All infants were received recombinant hepatitis B vaccine 10 μg within 12 h of birth, at week 4 and week 24, immunoglobulin G within 12 h of birth and were detected HBV markers at the range from 7 to 12 months after delivery. Results A total of 241 patients were finally enrolled, 139 patients in telbivudine group and 102 patients in control group. HBsAg negative rate of infants was 99.3% (135/136) in telbivudine group and was 91.9% (91/99) in control group after 7 months (P = 0.005), respectively. The incidence of undetectable HBV DNA levels (47.5%) was significantly lower in telbivudine-treated mothers than that in the controls (0%), and 75.5% patients alanine aminotransferase returned to normal in telbivudine group, and 51% in control group at delivery (P

Abstract Background Hepatitis B virus (HBV) infection is a major public health burden in China although it has steadily declined over the last two decades. A valid updated prevalence of HBV infection in China relies on a large sample size. Hence this study aimed to estimate HBV seroprevalence using a large inpatient population in Northeast China. Methods We consecutively enrolled 218,627 inpatients aged 1–70 years admitted to the First Hospital of Jilin University from January 2010 through December 2014. HBV serological markers were detected by chemiluminescence immunoassay (CLIA). Results Among the 218,627 collected samples, 16,254 (7.43%) were positive for HBsAg and 41.64% of patients were negative for all the HBV markers. The highest HBsAg prevalence was 10.05% in the 41–50 year age group and the lowest were 0.47% in the 1–10 and 2.35% in the 11–20 year age groups, respectively. HBsAg positivity was higher in males compared to females (8.94% vs. 5.80%). An HBsAg positivity of nearly 14% was found in middle-aged males, and positivity was 6.2% in females of childbearing age. One-third of this population only had a single HBsAb marker, which was also detected in 60% of patients aged under 20 years. Conclusion Though universal hepatitis B vaccination of infants has significantly reduced HBsAg prevalence in children, the number of most adults who have been infected with HBV remains steady. Extra care and resources should be provided to HBV-infected middle-aged males to stop the progression of chronic hepatitis B, and HBsAg positive females of childbearing age to block vertical HBV transmission.

Background: Chinese population has a high prevalence of chronic hepatitis B virus (HBV) infection, the impact of which on pregnancy outcome remains controversial. A single-center retrospective cohort study was performed in Kunming, a multi-ethnic city in south-western China to examine this issue.Methods: The singleton pregnancies delivering at ≥28 weeks gestation under our care in 2005-2017 constituted the study cohort. Maternal characteristics and pregnancy outcome were compared between mothers with and without seropositivity for hepatitis B surface antigen (HBsAg) determined at routine antenatal screening.Results: Among the 49,479 gravidae in the cohort, the 1624 (3.3%) HBsAg seropositive gravidae had a lower incidence of nulliparity (RR 0.963, 95% CI 0.935-0.992) and having received tertiary education (RR 0.829, 95% CI 0.784-0.827). There was no significant difference in the medical history, pregnancy complications, or labor or perinatal outcome, except that HBV carriers had significantly lower incidence of labor induction (RR 0.827, 95% CI 0.714-0.958) and of small-for-gestational age (SGA) infants (RR 0.854, 95% CI 0.734-0.994). On regression analysis, maternal HBV carriage was independently associated with spontaneous labor (aRR 1.231, 95% CI 1.044-1.451) and reduced SGA infants (aRR 0.842, 95% CI 0.712-0.997).Conclusions: Our 3.3% prevalence of maternal HBV infection was around the lower range determined in the Chinese population. The association with spontaneous labor and reduced SGA infants could have helped to promote the perpetuation of the infection through enhanced survival of the offspring infected at birth, thus explaining the high prevalence in the Chinese population. [ABSTRACT FROM AUTHOR]

Background: T cells play an important role in the prognosis of hepatitis B virus (HBV) infection, and are involved in the seroconversion of a patient from HBsAb negative to positive. To compare the T-cell receptor β-chain variable region (TcRBV) complementarity-determining region 3 (CDR3) in subjects with or without hepatitis B surface antigen (HBsAg) convert to hepatitis B surface antibody (HBsAb), the TcRBV was determined using high throughput sequencing (HTS).Methods: The clonotype and diversity of CDR3 in peripheral blood mononuclear cells of subjects with resolved acute hepatitis B (AHB, HBsAb+, HBsAg-) (n = 5), chronic hepatitis B (CHB, HBsAb-, HBsAg+) (n = 5), and healthy controls (HC, HBsAb-, HBsAg-) (n = 3) were determined and analyzed using HTS (MiSeq).Results: The overlapping rate of CDR3 clones of any two samples in AHB group was 2.00% (1.74% ~ 2.30%), CHB group was 1.77% (1.43% ~ 2.61%), and HC group was 1.82% (1.62% ~ 2.12%), and there was no significant difference among the three groups by Kruskal-Wallis H test. However, among the top 10 cumulative frequencies of clonotypes, only the frequency of clonotype (TcRBV20-1/BD1/BJ1-2) in AHB group was lower than that of HC group (P < 0.001). Moreover, exclude the 10 top clonotypes, there are 57 markedly different frequency of clones between AHB and CHB groups (18 clones up, 39 clones down), 179 (180-1) different clones between AHB and HC groups, and 134 different clones between CHB and HC groups. With regard to BV and BJ genotypes, there was no significant different frequency among the groups. Furthermore, there was no significant difference in the diversity of TcRBV CDR3 among the three groups (P > 0.05).Conclusions: Thus, there are 57 TcRBV clonotypes that may be related to HBsAg seroconversion of AHB subjects, but the diversity of TcRBV CDR3 is not significantly related to the HBsAb positive status. [ABSTRACT FROM AUTHOR]

Background: Evaluate the safety and efficacy of 104-week regimen of Telbivudine(LdT)-based optimization strategy for Chinese patients who have chronic hepatits B(CHB) with HBeAg-negative.Methods: This multi-center, open-label, prospective study enrolled 108 HBeAg-negative CHB patients who received LdT (600 mg/day) for 24 weeks, Adefovir (ADV) was added if HBV DNA remained detectable at week 24, otherwise LdT was maintained to use until 104 weeks. HBV DNA, alanine amino transferase (ALT), hepatitis B surface antigen(HBsAg), creatinine kinase(CK), and estimated glomerular filtration rate (eGFR) were measured, safety was assessed.Results: Eighty-eight patients (81%) had HBV-DNA undetectable at 24 weeks and maintained to receive LdT monotherapy until 104 weeks, whereas the other 20 patients had HBV-DNA detectable and ADV was used in combination. For all patients, 72% of patients reached ALT normalization at 24 weeks, which increased to 80% at 52 weeks and 104 weeks, respectively.. 81% of total patients had undetectable HBV-DNA at 24 weeks, 92% at 52 weeks, and 94% at 104 weeks. The HBsAg titre declined steadily from baseline to 104 weeks (3.62 vs. 2.98 log10 IU/mL, p < 0.05), and the eGFR increased steadily from baseline to 104 weeks (92.9 vs. 104.4 mL/min/1.73 m2, p < 0.05). Although 79 patients (73%) had at least one time of elevated CK, most of these patients had CK elevated in Grade 1/2.Conclusions: LdT was well tolerated and effective, and 94% of patients achieved virological suppression after 104 weeks.Trial Registration: This study was registered in clinicaltrials.gov on January 31, 2012 and the ID No. was NCT01521975 . [ABSTRACT FROM AUTHOR]

Abstract Background Persons with chronic hepatitis B (CHB) infection were reported to suffer severe disease after hepatitis E virus (HEV) superinfection, but the studies regarding HEV seroprevalence in this population were limited. A recent study in Vietnam found higher HEV seroprevalence among CHB patients compared with healthy controls. Methods A community-based case-control study was conducted in two counties of Shandong province, China, where hepatitis E incidence was at the highest (Rushan) and lowest (Zhangqiu) in the province based on data from routine public health surveillance. Four townships were selected randomly from each county and all residents in these townships were tested for hepatitis B surface antigen (HBsAg). Those tested positive for HBsAg (CHB group) and the 1:1 age and sex-matched HBsAg-negative residents (control group) were included. Anti-HEV IgM and IgG were tested and positive rates of IgG and IgM were compared between the CHB group and the control group. Results In total, 2048 CHB participants and 2054 controls were included in the study. In the CHB group, HEV IgG seroprevalence was 9.16% (95% CI: 7.47–11.09) in Zhangqiue and 38.06% (95% CI: 35.07–41.19) in Rushan (P

Background: Antiviral therapy is recommended for patients with immune-active chronic hepatitis B (CHB) to decrease the risk of liver-related complications. However, the outcomes of the pegylated IFN-α (PEG-IFN-α) therapy vary among CHB patients. We aimed to identify factors that can influence the outcomes in CHB patients who received antiviral PEG-IFN-α monotherapy.Methods: Thirty-two CHB patients who received PEG-IFN-α monotherapy were enrolled in this study. All of the patients underwent two liver biopsies at baseline and 6 months after the initiation of the therapy. CD8+ T cells, CD4+ T cells, CD68+ mononuclear cells, and PD-1 levels in the 64 liver biopsy specimens were examined via immunofluorescence.Results: The overall median frequency of CD8+ T cells in the liver tissues of 32 CHB patients significantly decreased at 6 months after the therapy initiation (p < 0.01). In the FIER (fibrosis and inflammation response with HBeAg seroconversion) group, CD8+PD-1+ T cells significantly decreased at 6 months (p < 0.05), while CD8+PD-1- T cells had no significant difference. On the contrary, in the FIENR (no fibrosis and inflammation response and HBeAg seroconversion) group, CD8+PD-1- T cells significantly decreased after 6 months of PEG-IFN-α treatment (p < 0.05), while CD8+PD-1+ T cells had no significant difference. In addition, the levels of CD68+ mononuclear cells in the FIER group showed an overall increasing trend after treatment (p < 0.05).Conclusions: The changes in the levels of CD8+PD-1+ T cells and CD68+ mononuclear cells may be related to the response to PEG-IFN-α therapy. [ABSTRACT FROM AUTHOR]

Background: Complete clearance of intracellular viruses depends on effector cells of innate and adaptive immune systems. This study aimed to identify the relationships among antiviral cytokines produced by natural killer (NK) and T cells and clinical-virological characteristics in untreated chronic hepatitis B (CHB) patients.Methods: We measured antiviral cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) produced by T, NK and natural killer T (NKT) cells, respectively, in a cohort with chronic hepatitis B virus (HBV) infection (CHB). We also correlated these cytokines with clinical-virological characteristics using a linear regression model.Results: levels of IFN-γ+ and TNF-α+ CD4+ and CD8+ T cells were significantly higher in immune active (IA) phase than in other phases. Immune tolerant (IT) patients showed the lowest expression of IFN-γ by NK and NKT cells, and TNF-α by NK cells. IFN-γ+, TNF-α+ and IL-2+ CD4+ and CD8+ T cells frequencies were similar between IA and gray zone (GZ) phases. Principal component analysis based on cytokines confirmed that most IT patients significantly differed from inactive carriers (IC) and IA patients, while GZ patients were widely scattered. Multivariate analysis showed both T and NK cells producing IFN-γ and TNF-α, but not IL-2, had significant association with serum alanine aminotransferase (ALT). Moreover, IFN-γ+ NKT cells were associated with HBV DNA, while IFN-γ+ CD4+ and CD8+ T cells were correlated with age.Conclusion: HBV clinical phases are characterized by distinct cytokine signatures, which showed relationship to viral features in these untreated CHB patients. [ABSTRACT FROM AUTHOR]

Background: Tanzania has a high prevalence (7.17%) of chronic hepatitis B infection. Mother to Child transmission is very common, resulting in high rate of chronic infections. Currently, there is no screening program for HBV in pregnant women. This study investigated the prevalence and risk factors for chronic HBV infection in pregnant women in a tertiary hospital in Mwanza, Tanzania.Methods: Seven hundred and forty-three women attending antenatal care and/or delivering at the Bugando Medical Centre were enrolled. All answered a questionnaire on sociodemographic and other risk factors and were tested for HBsAg using a rapid test. In HBsAg positive mothers, maternal blood and umbilical cord blood samples collected after delivery were analyzed for serological (HBsAg, HBeAg and anti-HBe) and virologic (HBV-DNA viral load and genotype) markers. All their babies were vaccinated within 24 h of delivery. The children were followed up at 3 years of age. Data was analyzed using the Mann-Whitney U-test, independent sample T-test and logistic regression.Results: Of the 743 participants, 22 (3%) were positive for HBsAg, and 2 (9%) had detectable HBe-antigen. Low condom use was the only statistically significant risk factor for chronic HBV infection (OR = 3.514, 95%CI = 1.4-8.0). Of 14 maternal blood samples genotyped, 10 (71%) were genotype A and 4 (29%) were genotype D. HBV-DNA was detected in 21/22 samples, with a median of 241 IU/ml (range: 27.4-25.9 × 107 IU/ml). Five (33%) of 15 available cord blood samples were positive for HBsAg and 10 (67%) were negative. At follow-up, one child showed chronic HBV infection characteristics, one had anti-HBs level of 7 mIU/ml and 5/7(71%) had protective anti-HBs levels (> 10 mIU/ml).Conclusion: This cohort of pregnant women showed a lower-intermediate prevalence of HBV of 3%. In the 3 years follow-up only 1 out of 7 children showed evidence of chronic HBV infection. The child's mother with high viral load (25.9 × 107 IU/ml), was positive for HBeAg with a high degree of sequence similarity suggesting vertical transmission. These results highlight a need for improved diagnosis and treatment of HBV infection in pregnant women in Tanzania, in order to prevent vertical transmission. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection is a major public health burden in China although it has steadily declined over the last two decades. A valid updated prevalence of HBV infection in China relies on a large sample size. Hence this study aimed to estimate HBV seroprevalence using a large inpatient population in Northeast China.Methods: We consecutively enrolled 218,627 inpatients aged 1-70 years admitted to the First Hospital of Jilin University from January 2010 through December 2014. HBV serological markers were detected by chemiluminescence immunoassay (CLIA).Results: Among the 218,627 collected samples, 16,254 (7.43%) were positive for HBsAg and 41.64% of patients were negative for all the HBV markers. The highest HBsAg prevalence was 10.05% in the 41-50 year age group and the lowest were 0.47% in the 1-10 and 2.35% in the 11-20 year age groups, respectively. HBsAg positivity was higher in males compared to females (8.94% vs. 5.80%). An HBsAg positivity of nearly 14% was found in middle-aged males, and positivity was 6.2% in females of childbearing age. One-third of this population only had a single HBsAb marker, which was also detected in 60% of patients aged under 20 years.Conclusion: Though universal hepatitis B vaccination of infants has significantly reduced HBsAg prevalence in children, the number of most adults who have been infected with HBV remains steady. Extra care and resources should be provided to HBV-infected middle-aged males to stop the progression of chronic hepatitis B, and HBsAg positive females of childbearing age to block vertical HBV transmission. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B (CHB) related morbidity and mortality can be reduced through risk group screening, linkage to care and anti-viral treatment. This study estimates the number of CHB cases among foreign-born (migrants) in the European Union and European Economic Area (EU/EEA) countries in order to identify the most affected migrant populations. Methods: The CHB burden was estimated by combining: demographic data on migrant population size by country of birth in the EU/EEA, extracted from European statistical databases; and CHB prevalence in migrants' countries of birth and in EU/EEA countries, derived from a systematic literature search. The relative contribution of migrants from endemic countries to the total CHB burden in each country was also estimated. The reliability of using country of birth prevalence as a proxy for prevalence among migrants was assessed by comparing it to the prevalence found in studies among migrants in Europe. Results: An estimated 1-1.9 million CHB-infected migrants from endemic countries (prevalence ≥2%) reside in the EU/ EEA. Migrants from endemic countries comprise 10.3% of the total EU/EEA population but account for 25% (15%-35%) of all CHB cases. Migrants born in China and Romania contribute the largest number of infections, with over 100,000 estimated CHB cases each, followed by migrants from Turkey, Albania and Russia, in descending order, with over 50,000 estimated CHB cases each. The CHB prevalence reported in studies among migrants in EU/EEA countries was lower than the country of birth prevalence in 9 of 14 studies. Conclusions: Migrants from endemic countries are disproportionately affected by CHB; their contribution however varies between EU/EEA countries. Migrant focused screening strategies would be most effective in countries with a high relative contribution of migrants and a low general population prevalence. In countries with a higher general population prevalence and a lower relative contribution of migrants, screening specific birth cohorts may be a more effective use of scarce resources. Quantifying the number of CHB infections among 50 different migrant groups residing in each of the 31 EU/EEA host countries helps to identify the most affected migrant communities who would benefit from targeted screening and linkage to care. [ABSTRACT FROM AUTHOR]

Background: Because of the high prevalence and absence of cure for infection, chronic hepatitis B virus (HBV) infection has been acknowledged as a pressing public health issue. Toll-like receptors (TLRs) activate the human innate immune system and the polymorphisms in TLRs may alter their function. The present study aimed to investigate the association between TLR polymorphisms and disease progression of chronic HBV infection.Methods: During the study period, 211 treatment-naïve patients with chronic HBV infection were recruited, and blood samples were collected from each individual. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was employed to genotype the selected TLR polymorphisms after human genome extraction. In addition, HbsAg, TNF-α, and IL-6 levels were quantified using enzyme linked immunosorbent assay (ELISA). Statistical analyses were conducted to investigate the association between TLR polymorphisms and hepatitis activity, liver function parameters, HbsAg level, and cytokine level.Results: We did not observe any mutations in rs4986790, rs4986791, and rs5743708 among all study subjects. A logistic regression revealed that mutations in rs3804099 and rs4696480 were associated with milder hepatitis activity. Consistent with the logistic regression, improved liver function parameters and reduced level of both HbsAg and cytokines were also correlated with the mutant carriers of rs3804099 and rs4696480.Conclusions: TLR mutations were significantly associated with milder hepatitis activity among patients with chronic HBV infection. Therefore, we conclude that the activation of TLR pathways may further intensify the inflammation of hepatocytes, and leads to progression of disease. [ABSTRACT FROM AUTHOR]

A large burden of undiagnosed hepatitis virus cases remains globally. Despite the 257 million people living with chronic hepatitis B virus infection, and 71 million with chronic viraemic HCV infection, most people with hepatitis remain unaware of their infection. Advances in rapid detection technology have created new opportunities for enhancing access to testing and care, as well as monitoring of treatment. This article examines a range of other technological innovations that can be leveraged to provide more affordable and simplified approaches to testing for HBV and HCV infection and monitoring of treatment response. These include improved access to testing through alternative sampling methods (use of dried blood spots, oral fluids, self-testing) and combination rapid diagnostic tests for detection of HIV, HBV and HCV infection; more affordable options for confirmation of virological infection (HBV DNA and HCV RNA) such as point-of-care molecular assays, HCV core antigen and multi-disease polyvalent molecular platforms that make use of existing centralised laboratory based or decentralised TB and HIV instrumentation for viral hepatitis testing; and finally health system improvements such as integration of laboratory services for procurement and sample transportation and enhanced data connectivity to support quality assurance and supply chain management. [ABSTRACT FROM AUTHOR]

Background: For hepatitis B patients who do not meet the treatment criteria recommended by guidelines, therapy decisions depend on hepatic histology. Angiopoietin-like protein 2 (Angptl2) is a mediator of chronic inflammation that contributes to extracellular matrix remodeling. The aim of this study was to explore the predictive value of Angptl2 as a novel biomarker of liver histology.Methods: Hepatitis B patients with normal to minimally raised ALT were recruited. Serum Angptl2 concentrations were detected using commercial ELISA kit. The fibrosis score were assessed according to Ishak criteria. Significant fibrosis was defined as ISHAK score ≥ 3.Results: Of 460 patients, 223 cases served as training cohort and 237 ones as validation cohort. Serum Angptl2 concentration was significantly associated with fibrosis scores in both training and validation group. Angptl2 combined index (ACI) for assessing significant fibrosis was developed from training cohort, based on Angptl2 and conventional variables. ACI showed areas under receiver-operating characteristic curve (AUC) of 0.835 for predicting significant fibrosis, which was superior to APRI (AUC = 0.776, P = 0.049), FIB-4 (AUC = 0.750, P = 0.010), Hui model (AUC = 0.756, P = 0.028), and had a better trend than Forn's index (AUC = 0.796, P = 0.083) in training cohort. Finally, validation cohort revealed its robustness and reliability.Conclusion: Higher Angptl2 level represents as a potential biomarker independently associated with fibrosis stages. Compared with APRI, Hui model, FIB-4, Forn's index, ACI did better in diagnosing significant fibrosis in hepatitis B patients.Trial Registration: The complete clinical trials protocol is available by request at clinicaltrials.gov ( NCT01962155 ) and chictr.org ( ChiCTR-DDT-13003724 ). [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection is a major public health problem globally. HBV genotypes and subgenotypes influence disease transmission, progression, and treatment outcome. A study was conducted among treatment naive chronic HBV patients in southern Vietnam to determine the genotypes and subgenotypes of HBV.Methods: A prospective, exploratory study was conducted among treatment naïve chronic HBV patients attending at the Hospital for Tropical Diseases, in Ho Chi Minh City, Vietnam during 2012, 2014 and 2016. HBV DNA positive samples (systematically selected 2% of all treatment naïve chronic patients during 2012 and 2014, and 8% of all treatment naïve chronic patients during 2016) were subjected to whole genome sequencing (WGS) either by Sanger or Illumina sequencing. WGS was used to define genotype, sub-genotype, recombination, and the prevalence of drug resistance and virulence-associated mutations.Results: One hundred thirty five treatment naïve chronic HBV patients including 18 from 2012, 24 from 2014, and 93 from 2016 were enrolled. Of 135 sequenced viruses, 72.6% and 27.4% were genotypes B and C respectively. Among genotype B isolates, 87.8% and 12.2% were subgenotypes B4 and B2 respectively. A G1896A mutation in the precore gene was present in 30.6% of genotype B isolates. The genotype C isolates were all subgenotype C1 and 78.4% (29/37) of them had at least one basal core promoter (BCP) mutation. A1762T and G1764 T mutations and a double mutation (A1762T and G1764 T) in the BCP region were significantly more frequent in genotype C1 isolates (p < 0.001).Conclusion: HBV genotype B including subgenotype B4 is predominant in southern Vietnam. However, one fourth of the chronic HBV infections were caused by subgenotype C1. [ABSTRACT FROM AUTHOR]

Background: Treatment for chronic hepatitis B (CHB) is virtually absent in sub-Saharan Africa. Here we present early experiences from a pilot program for treatment of CHB in Ethiopia.Methods: Adults (≥18 years) with CHB were included in a cohort study at St. Paul's Hospital Millennium Medical College, Addis Ababa, from February 2015. The baseline assessment included liver function tests, viral markers and transient elastography (Fibroscan 402, Echosense, France). Logistic regression models were used to identify predictors of fibrosis. Tenofovir disoproxil fumarate (TDF) was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. The initial 300 patients underwent a more comprehensive evaluation and are presented here.Results: One-hundred-and-thirty-eight patients (46.0%) were women and median age was 30 years (interquartile range 26-40). Co-infections were rare: four patients (1.3%) were anti-HCV positive, 11 (3.7%) were anti-HDV positive, whereas 5 (1.7%) had HIV-infection. The majority were hepatitis B e-antigen (HBeAg) negative (n = 262; 90.7%) and had a normal (≤40 U/L) alanine aminotransferase (ALT) (n = 245; 83.1%). Of 268 patients with a valid Fibroscan result, 79 (29.5%) had significant fibrosis (>7.9 kPa). Independent predictors of fibrosis were male sex, age > 35 years and viral load >20,000 IU/ml. In total, 74 patients (24.7%) started TDF therapy, of whom 46 (62.2%) had cirrhosis.Conclusions: The majority were HBeAg negative and had normal ALT. However, one quarter of the patients were in need of antiviral treatment, underscoring the need to scale up CHB treatment on the African continent.Trial Registration: NCT02344498 ( ClinicalTrials.gov identifier). Registered 16 January 2015. [ABSTRACT FROM AUTHOR]

Background: The concentrations of hepatitis B virus (HBV) DNA and surface antigen (HBsAg) are two critical virological variables to be monitored in chronic hepatitis B. HBsAg is derived from the HBV genome. Thus, higher HBV-DNA concentrations should implicate higher HBsAg levels. Nevertheless, the two variables do not manifest a simple linear relationship due to elusive host factor involvements. The aim of this study was to address the discrepancy of HBV DNA and HBsAg levels by a quantitative modeling of HBsAg concentrations.Methods: Pretreatment hematological, histological and virus serological records of 327 chronic hepatitis B patients were reviewed. Two independent patient cohorts were used for validation.Results: Univariate/multivariate analysis showed that ISHAK fibrosis stages, HBV-DNA levels and hepatitis e-antigen status were independently associated with HBsAg concentrations. In agreement with the natural history of chronic hepatitis B, HBsAg concentrations were negatively correlated with ISHAK fibrosis stages (adjusted P = 0.002). Subgroup analysis showed that significant HBsAg-DNA correlation existed in high-viral-titer patients with HBV-DNA > 6 log10 IU/mL (P < 0.001), but not in low-viral-titer patients with HBV-DNA ≤ 6 log10 IU/mL (P = 0.076). A backward stepwise linear regression analysis in the low-viral-titer subgroup revealed a significant correlation between HBsAg levels and a linear combination of HBV-DNA levels and platelet counts. A biphasic model was thus established to accommodate patients with high and low HBV-DNA titers:[Formula: see text] The estimated HBsAg concentrations correlated well with the measured HBsAg levels not only in the model construction cohort (N =327, P < 0.001), but also in two validation cohorts comprising respectively the patients who had received pretreatment liver biopsy assessments (N = 45, P = 0.001), and the treatment-naïve patients who had not received liver biopsy (N = 80, P < 0.001).Conclusion: HBsAg concentrations can be quantitatively estimated by viral DNA concentrations and human platelet counts. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B virus(HBV) infection is a major cause of liver related morbidity and mortality. HBV infection remains largely underdiagnosed in Asian American population, and it is also poorly linked to clinical care. We, therefore, assessed the HBV prevalence and evaluated linkage to care among Korean Americans in order to develop strategic plans to reduce the impact of HBV in a high risk community.Methods: Serologic screening and survey were provided to 7157 Korean American adults (age 21-100) in New Jersey between December 2009 and June 2015. All participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core IgG antibody (anti-HBc). Additional survey was conducted on the subjects chronically infected with HBV on their history of infection. Self-administered questionnaires were employed to evaluate demographic and epidemiologic characteristics.Results: Of those 7157screened, 171 (2.4 %) were HBV infected, 2736(38.2 %) were susceptible to HBV, and 4250(59.4 %) were immune. The prevalence of chronic HBV varied between the age groups: 1.18 % (age21-30); 2.53 % (age 31-40); 2.76 % (age 41-50); 2.90 % (age 51-60); 2.06 % (age 61-70); and 1.37 % (age 71-100). The rate of HBsAg was significantly higher in males (3.04 %) as compared to females (1.93 %). At least 75 % of these HBV infected subjects had been previously diagnosed, but were not engaged in care.Conclusion: This screening study suggests that the HBV prevalence in Korean Americans is significantly lower than currently understood. On the other hand, many of the individuals chronically infected with HBV cannot access care, suggesting a poor linkage-to-care (LTC). Further, a large percentage of the population is still susceptible to HBV. Study findings will be used to develop strategies to tailor community-based HBV screenings and LTC to the high risk populations. [ABSTRACT FROM AUTHOR]

Background: Interleukin-33 (IL-33) and ST2 have been demonstrated to be associated with liver damage. However, their potential value in hepatitis B virus (HBV) infection remains unknown. This study was designed to investigate the change of serum IL-33 and ST2 levels in the natural course of chronic HBV infection.Methods: A total of 120 patients with chronic hepatitis B (CHB), 20 chronic hepatitis B virus carriers in immunotolerant phase and 28 healthy controls were enrolled in this study. All patients with CHB were divided into four groups according to their serum ALT levels. The serum levels of IL-33 and ST2 of all participants were determined by enzyme-linked immunosorbent assay, and compared between each two out of those six groups.Results: No significant differences were found in serum levels of IL-33 and ST2 between the group of CHB with ALT 1-2 upper limit of normal and the healthy controls (P = 0.354 for IL-33 and P = 0.815 for ST2). Other than that, there were significant differences when serum levels of IL-33 and ST2 were compared between any other two out of those six groups (P < 0.05, respectively). The overall correlation analysis indicated that changes of serum IL-33 and ST2 levels were positively associated with ALT levels in patients with chronic HBV infection (rs = 0.879, P < 0.001 for IL-33 and rs = 0.923, P < 0.001 for ST2). No significant differences were found when the serum levels of ALT, IL-33 and ST2 were compared between patients with HBeAg-positive CHB and HBeAg-negative CHB.Conclusions: Our study revealed that the serum levels of IL-33 and ST2 varied in different courses of chronic hepatitis B virus infection. The serum levels of IL-33 and ST2 elevated as serum ALT levels increased in patients with CHB. They might indicate liver damage for patients with CHB, just like ALT. [ABSTRACT FROM AUTHOR]

Background: Although, chronic hepatitis B (HBV) is considered to be of significant public health importance in Ghana, not many reviews detailing the burden (prevalence) of the disease have been conducted. This study was aimed at summarizing the available information and to make an accurate estimate of HBV infection prevalence in Ghana over the last two decades (1995-2015).Methods: A systematic search was conducted in PubMed, ScienceDirect, Google Scholar and Africa Journals Online (AJOL) databases to retrieve primary studies published between 1st January 1995 and 4th October 2015, assessing the prevalence of HBV among populations in Ghana. This was supplemented by a manual search of retrieved references.Results: Thirty (30) studies across all the ten (10) regions of Ghana and involving an overall population size of 105,435 were analyzed. The national prevalence of HBV as determined by HBsAg seropositivity was 12.3%. HBV prevalence among voluntary blood donors (VBDs), replacement blood donors (RBDs) and pregnant women were 10.8, 12.7 and 13.1% respectively. HBV infection prevalence was highest among studies published within the period 1995-2002 (17.3%), followed by those published within 2003-2009 (14.7%) and the lowest prevalence rate being recorded across studies published in the period 2010-2015 (10.2%). Regional prevalence were determined for Ashanti, Greater Accra, Eastern, Northern, central and Brong-Ahafo regions as 13.1, 10.6, 13.6, 13.1, 11.5 and 13.7% respectively. No aggregate data were derived for Volta, Western, Upper East and Upper West regions. Higher prevalence of HBV infection was attained for rural (13.3%) compared to urban settings (12.2%). Across the country, highest HBV infection prevalence rates were recorded in persons within the age group 16-39 years.Conclusion: Hepatitis B infection is clearly an important public health problem in Ghana. The burden of the disease as dictated by a high prevalence rate calls for urgent public health interventions and strategic policy directions to controlling the disease to avert any potential future explosion. [ABSTRACT FROM AUTHOR]

Background: We evaluated the short-term spontaneous fluctuations of HBV DNA and HBsAg levels in Senegalese patients with chronic infection with hepatitis B virus and normal ALT and determined factors related to these fluctuations. Method: A total of 87 patients with persistent normal ALT values were enrolled in the study. Serum samples were obtained at three different visits, with an interval of 2 months (M0, M2, and M4), and without initiating anti HBV treatment. Levels of HBV DNA, quantitative HBsAg, ALT and AST, genotyping and viral DNA mutations were analyzed. Results: Among the 87 patients, genotype E was predominant (75%). The median HBV DNA level was 2.9 log10 IU/mL [2.2-3.4], 2.7 log10 IU/mL [2.1-3.6] and 2.7 log10 IU/mL [2.1-3.4] at M0, M2 and M4, respectively. The values ranged from <1.1 to 7 log10 IU/mL and 55 (63%) had HBV DNA fluctuations ≥ 0.5 log10 IU/mL between two visits. Patients in whom HBV DNA fluctuated ≥0.5 log10 IU/mL between M0 and M2 also had significant fluctuations between M2 and M4, while patients with stable HBV DNA between M0 and M2 showed a stable viral load between M2 and M4. The only factor found to be associated with HBV DNA fluctuations ≥ 0.5 log10 IU/mL was a low BMI (<21 kg/ m²). HBsAg levels were not correlated with HBV DNA levels. Conclusion: Sixty-three percent of the enrolled Senegalese population showed a large, short-term fluctuation of HBV DNA levels. Such fluctuations may have an impact on therapeutic management, requiring closer monitoring. [ABSTRACT FROM AUTHOR]

Background: Current estimates suggest over 218,000 individuals in Australia are chronically infected with hepatitis B virus. The majority of these people are migrants and refugees born in hepatitis B endemic countries, where attitudes towards health, levels of education, and English proficiency can be a barrier to accessing the Australian health care system, and best managing chronic hepatitis B. This study aimed to assess the knowledge of transmission and consequences of chronic hepatitis B among these patients. Method: A prospective study was conducted between May and August 2012. Patients with chronic hepatitis B were recruited from three Royal Melbourne Hospital outpatient clinics. Two questionnaires were administered. Questionnaire 1, completed during observation of a prospective participants' consultation, documented information given to the patient by their clinician. After the consultation, Questionnaire 2 was administered to assess patient demographics, and overall knowledge of the effect, transmission and treatment of hepatitis B. Results: 55 participants were recruited. 93% of them were born overseas, 17% used an interpreter, and the average time since diagnosis was 9.7 years. Results from Questionnaire 1 showed that the clinician rarely discussed many concepts. Questionnaire 2 exposed considerable gaps in hepatitis B knowledge. Few participants reported a risk of cirrhosis (11%) or liver cancer (18%). There was a high awareness of transmission routes, with 89% correctly identifying sexual transmission, 93% infected blood, and 85% perinatal transmission. However, 25% of participants believed hepatitis B could be spread by sharing food, and over 50% by kissing and via mosquitoes. A knowledge score out of 12 was assessed for each participant. The average score was 7.5. Multivariate analysis found higher knowledge scores among those with a family member also diagnosed with chronic hepatitis B and those routinely seeing the same clinician (p = 0.009 and p = 0.002, respectively). Conclusion: This is the largest Australian study assessing knowledge and understanding of the effect, transmission, and treatment of hepatitis B among chronically infected individuals. The findings highlight the knowledge gaps and misconceptions held by these patients, and the need to expand education and support initiatives. [ABSTRACT FROM AUTHOR]

Background: The sodium taurocholate co-transporting polypeptide, encoded by SLC10A1, was identified as a functional receptor for hepatitis B virus (HBV). The objective of this study was to determine if there was an association of the Ser267Phe variant (rs2296651) with HBV infection status in Moroccan patients.Methods: Using a TaqMan 5' allelic discrimination assay, the Ser267Phe variant was genotyped in 286 chronic hepatitis B patients, 135 individuals with spontaneous clearance from HBV infection and 109 healthy controls negative for hepatitis B serological markers.Results: In this cohort, we detected only wild-type genotype (S267S) in all groups. This polymorphism was not associated with the HBV infection status in Moroccan patients.Conclusions: The S267F variant is absent among Moroccans regardless of chronic HBV infection status. [ABSTRACT FROM AUTHOR]

Background Hepatitis B virus (HBV) DNA levels are crucial for managing chronic hepatitis B (CHB). It was unclear whether Daan real-time polymerase chain reaction test (Daan test) or COBAS TaqMan HBV DNA Test (Cobas TaqMan) was superior in measuring different HBV DNA levels in clinical specimens. Methods We enrolled 67 treatment-naïve, HBV surface antigen-positive CHB patients (high baseline viral levels) who received either lamivudine/adefovir or entecavir. Serum samples were tested at baseline and treatment week 24 using the Daan test and Cobas TaqMan. Results In the 67-baseline samples, the HBV DNA levels with the Cobas TaqMan (7.90 ± 0.73 log10 IU/mL) were significantly greater than those of the Daan test (7.11 ± 0.44 log10 IU/mL; P < 0.001). Of the 67 24-week samples (low viral levels), the Cobas TaqMan detected 59 (88.1%; 8 undetected); the Daan test detected 33 (49.3%; 34 undetected; P < 0.001). The Cobas TaqMan detected HBV DNA in 26 of 34 samples undetectable by the Daan test (range, 1.4– 3.7 log10 IU/mL) or 38% of samples (26/67). The reductions in viral load after 24 weeks of oral antiviral treatment in the 33 samples that were positive for both the Daan test and the Cobas TaqMan test were significantly different (3.59 ± 1.11 log10 IU/mL versus 4.87 ± 1.58 log10 IU/mL, respectively; P = 0.001). Spearman correlation analysis showed positive correlation between results from two tests (rp = 0.602,P<0.001). The HBV genotypes and the anti-viral treatment did not affect the measurements of the HBV DNA by the Daan assay and the Cobas Taqman assay. Conclusion The Cobas Taqman was more sensitive at low viral loads than the Daan test and the change from complete to partial virological response could affect clinical decisions. The Cobas Taqman may be more appropriate for detection of HBV DNA levels. [ABSTRACT FROM AUTHOR]

Background: The durability of off-treatment virologic responses has not been fully elucidated in chronic hepatitis B (CHB) patients who have previously achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy. This study aimed to assess off-treatment virologic relapse rates and to characterize the outcomes of subsequent re-treatment in CHB patients who have discontinued oral NA following complete virologic suppression. Methods: Ninety-five CHB patients who showed complete virologic suppression were withdrawn from NAs: entecavir, lamivudine, and clevudine in 67, 15, and 13 patients, respectively. Consolidation therapy was given for 6 and 12 months for HBeAg-positive and -negative CHB, respectively, before cessation. Virologic relapse was managed with the same NA that had induced complete virologic response before discontinuation. Results: The cumulative rates of virologic relapse at 12 and 24 months were 73.8% and 87.1%, respectively. The relapse rates were independent of HBeAg positivity, HBeAg seroconversion, and type of oral NA. In a multivariate analysis, duration of oral NA therapy was the only significant predicting factor associated with off-treatment virologic relapse. Although the majority of patients regained complete virologic suppression, some patients did not respond to re-treatment with the initial NA and developed genotypic resistance. Conclusions: NA consolidation therapy for 6 and 12 months is associated with high off-treatment virologic relapse in HBeAg-positive and -negative CHB patients, respectively. Drugs with high genetic barriers to resistance should be considered as a rescue therapy for off-treatment relapse in CHB. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B e Antigen (HBeAg)-negative chronic hepatitis B (CHB) patients have an active liver disease with a high risk of progression to decompensated cirrhosis and hepatocellular carcinoma. The management strategy for HBeAg-negative CHB patients treated with nucleos(t)ide analogues (NUCs) is a topic of concern. To observe the outcomes for this population after NUCs withdrawal, HBeAg-negative CHB patients with loss of hepatitis B surface antigen (HBsAg) or sustained undetectable HBV DNA levels who had discontinued NUCs therapy were included in the study. Methods: A total of 66 patients (2 patients with HBsAg loss and 64 patients with sustained undetectable HBV DNA levels) were examined. HBV DNA levels and alanine aminotransferase (ALT) levels were monitored regularly after discontinuation of NUCs therapy. Relapse was defined as HBV DNA levels >2,000 IU/mL while off therapy in at least two determinations more than 4 weeks apart. Results: The time to achieve undetectable HBV DNA levels was 14 weeks (interquartile range (IQR): 12-24 weeks). The time until consolidation therapy was 144 weeks (IQR: 96-168 weeks). No relapses occurred in either of the HBsAg loss patients. Among the 64 patients with undetectable HBV DNA levels, 19 (29.7%) patients demonstrated evidence of relapse. All the relapses occurred within 96 weeks after discontinuation. The median duration of relapse was 36 weeks (IQR: 12-48 weeks). Elevation of HBV DNA and ALT levels over baseline was only observed in 10% of the relapse patients. There were no significant differences among the baseline characteristics (sex, HBV genotype, age, or ALT level) or the time until consolidation therapy between relapse and sustained-response patients. Conclusions: NUC discontinuation is feasible after achieving undetectable HBV DNA levels in HBeAg-negative CHB patients. Prolonging the time until consolidation therapy may be a good strategy to decrease the rate of relapse. More than 96 weeks of sustained response is a predictive marker of long-term sustained response. [ABSTRACT FROM AUTHOR]

Background: In Australia, higher rates of chronic hepatitis B (HBsAg) have been reported among Aboriginal and Torres Strait Islander (Indigenous) compared with non-Indigenous people. In 2000, the Australian government implemented a universal infant/adolescent hepatitis B vaccination program. We undertook a systematic review and meta-analysis to assess the disparity of HBsAg prevalence between Indigenous and non-Indigenous people, particularly since 2000. Methods: We searched Medline, Embase and public health bulletins up to March 2011. We used meta-analysis methods to estimate HBsAg prevalence by Indigenous status and time period (before and since 2000). Results: There were 15 HBsAg prevalence estimates (from 12 studies) among Indigenous and non-Indigenous people; adults and pregnant women (n = 9), adolescents (n = 3), prisoners (n = 2), and infants (n = 1). Of these, only one subgroup (adults/pregnant women) involved studies before and since 2000 and formed the basis of the meta-analysis. Before 2000, the pooled HBsAg prevalence estimate was 6.47% (95% CI: 4.56-8.39); 16.72% (95%CI: 7.38-26.06) among Indigenous and 0.36% (95%CI:-0.14-0.86) in non-Indigenous adults/pregnant women. Since 2000, the pooled HBsAg prevalence was 2.25% (95% CI: 1.26-3.23); 3.96% (95%CI: 3.15-4.77) among Indigenous and 0.90% (95% CI: 0.53-1.28) in non-Indigenous adults/pregnant women. Conclusions: The disparity of HBsAg prevalence between Indigenous and non-Indigenous people has decreased over time; particularly since the HBV vaccination program in 2000. However HBsAg prevalence remains four times higher among Indigenous compared with non-Indigenous people. The findings highlight the need for opportunistic HBV screening of Indigenous people to identify people who would benefit from vaccination or treatment. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to prospectively investigate the value of real-time ultrasound elastography (RTE) for the diagnosis of liver fibrosis (LF) in patients with chronic hepatitis B (CHB), to correlate the elastography findings with the histologic stage of LF and to compare RTE findings with those from noninvasive tests of LF calculated using laboratory blood parameters.Methods: Liver biopsies, laboratory blood testing, and RTE were performed in 91 patients with CHB. The LF index (LFI) was calculated using a multiple linear regression equation involving 11 parameters, which represented the degree of LF. The higher the LFI is, the greater the degree of LF.Results: The mean aspartate aminotransferase-to-platelet ratio index (APRI) and the mean fibrosis index based on four factors (FIB-4) were significantly different for the 5 stages of LF, respectively. The APRI (r = 0.43, P = 0.006), FIB-4 (r = 0.51, P = 0.012) and LFI (r = 0.562, P = 0.004) were correlated with the stages of LF. For discriminating stage F0 from F1, only the LFI had significant power (P = 0.026) for predicting stage F1. For discriminating stage F4 from F3, only the LFI had statistically significant power (P = 0.024) in predicting stage F4. The areas under the receiver operating characteristic curves (AUCs) of the LFI for diagnosing significant, advanced LF and liver cirrhosis were significantly higher than those of the APRI and FIB-4, and the LFI had better sensitivity and specificity.Conclusions: The LFI calculated by RTE is reliable for the assessment of LF in patients with CHB and has better discrimination power than the APRI and FIB-4. [ABSTRACT FROM AUTHOR]

Background: Chronic infection with hepatitis B virus (HBV) is a serious global health problem. Persistence of the virus occurs as a result of stability of the replication intermediate comprising covalently closed circular DNA (cccDNA). Development of drugs that are capable of disabling this cccDNA is vital.Methods: To investigate an epigenetic approach to inactivating viral DNA, we engineered transcriptional repressors that comprise an HBV DNA-binding domain of transcription activator like effectors (TALEs) and a fused Krüppel Associated Box (KRAB). These repressor TALEs (rTALEs) targeted the viral surface open reading frame and were placed under transcription control of constitutively active or liver-specific promoters.Results: Evaluation in cultured cells and following hydrodynamic injection of mice revealed that the rTALEs significantly inhibited production of markers of HBV replication without evidence of hepatotoxicity. Increased methylation of HBV DNA at CpG island II showed that the rTALEs caused intended epigenetic modification.Conclusions: Epigenetic modification of HBV DNA is a new and effective means of inactivating the virus in vivo. The approach has therapeutic potential and avoids potentially problematic unintended mutagenesis of gene editing. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) is a hepatotropic deoxyribonucleic acid (DNA) virus which causes death. More than 300 million people have chronic liver infections globally and about 600,000 people die annually from acute or chronic complications of hepatitis B infection. Recent studies conducted in Ethiopia showed moderate endemicity (3-7.8%) of HBV among pregnant women. However, there is paucity of information on sero- prevalence of HBV and associated factors among pregnant women at Gambella town. The aim of this study is to assess sero-prevalence of hepatitis surface antigen (HBsAg) and associated factors among pregnant women in Gambella Hospital.Methods: Hospital based cross-sectional study was conducted in a total of 253 pregnant women from March 10-April 15, 2017. Socio-demographic characteristics and risk factors were collected through face to face interview using structured questionnaire. HBV infection was determined using Eugene strip test. Logistic regression analysis was used to determine association between HBsAg sero-positivity and various factors. Findings were presented using 95% CI of Crude Odds Ratios (COR) and Adjusted Odds Ratios (AOR).Result: The overall sero- prevalence of HBV infection was 7.9% (95% CI, 4.7-11.9), which indicates intermediate endemicity. History of abortion (AOR = 3.56:1: 95% CI, 1.24-10.22), occupation (AOR = 8.36:95% CI, 1.67-41.96) and multiple sexual partner (AOR = 17.38: 95% CI, 4.48-67.49) had statistical significant association with HBsAg sero-positivity.Conclusion: HBV sero-prevalence in pregnant women shows intermediate endemicity. Hence health education on having single sexual partner and risk factors of abortion should be given. In addition, routine screening and immunization of pregnant women for HBV infection should be strengthen. [ABSTRACT FROM AUTHOR]

Background: Due to no clinical symptoms in the compensated stage of cirrhosis, it is usually diagnosed when decompensated complications occur. In this study, the noninvasive circulating biomarkers for early detection to compensated stage of cirrhosis in patients with chronic HBV (hepatitis B virus) infection was explored.Methods: According to the Guideline of Prevention and Treatment of Chronic Hepatitis B (2015 Update), 78 patients with CHB (chronic hepatitis B) were divided into mild group, moderate-to-advanced group, while 73 patients with HBV-related cirrhosis were divided into compensated group and decompensated group. Nineteen cytokines and chemokines, four serum liver fibrosis markers were measured using chemiluminescence. The expression of CCL5 in liver tissue was determined with immunohistochemistry.Results: The CCL5 expression level in serum increased in CHB patients with aggravated liver injury and significantly decreased in cirrhosis patients with advanced liver fibrosis. ROC analysis revealed that the serum levels of CCL5, HA and MIP-1β were effective in distinguishing patients with cirrhosis from patients with CHB, especially for CCL5. Increasing serum level of CCL5 in CHB patients was severely associated with disease progression.Conclusions: The serum levels of CCL5, HA and MIP-1β maybe used to distinguish cirrhosis from CHB patients, moreover, CCL5 was the most reliable marker. The increasing serum levels of CCL5 were significantly related to disease progression in CHB patients. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) reactivation is one of the most common precipitating events associated with acute decompensation (AD) or acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB)-related cirrhotic patients. However, whether their serum HBV deoxyribonucleic acid (DNA) levels are associated with ACLF incidence and short-term mortality rate is still ambiguous.Methods: The ACLF incidences, 28-day and 90-day liver transplantation (LT)-free mortality rates, previous nucleoside/nucleotide analogues (NUCs) treatments and serum HBV DNA levels at admission (ad-levels) of 111 hospitalized patients with AD of CHB-related cirrhosis were analyzed.Results: 43 (38.7%) patients developed ACLF. The 28-day and 90-day LT-free mortality rates of the ACLF cases were 15.4 and 40.9%, respectively. Though NUCs inhibited HBV replication effectively, there were no differences in the ACLF incidence between antiviral treatment-naïve patients and NUCs treatment-experienced patients with or without interruptions (37.5, 41.7 and 45.5%, respectively, P>0.05). The serum HBV DNA ad-level was similar between the patients with and without ACLF development (logarithms: 4.50 ± 1.96 vs 4.32 ± 1.99; ≥2000 IU/ml: 67.4% vs 67.6%; both P>0.05), so was between the ACLF patients died or survived in 28 or 90 days (logarithms: 4.31 ± 1.91 vs 5.54 ± 2.53, 4.81 ± 1.76 vs 4.84 ± 2.40, respectively, both P>0.05).Conclusion: Serum HBV DNA ad-level and previous NUCs treatment are not associated with incidence of ACLF and short-term mortality rate in the hospitalized patients with AD of CHB-related cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Various integrated care models have been used to improve treatment completion of medications for chronic hepatitis B virus (HBV), chronic hepatitis C virus (HCV), Mycobacterium tuberculosis (TB), and Human immunodeficiency virus (HIV) among people with substance use disorders (SUD). We have conducted a systematic review to evaluate whether integrated models have impacts of the treatment of infectious diseases among marginalized people with SUD.Methods: We searched MEDLINE/PubMed (1946 to 2018, on July 26, 2018) and Embase (from 1974 to 2018, on July 26, 2018) for randomized controlled trials (RCTs) and cohort studies evaluating diverse integrated models' effects on sustained virological response (SVR), HIV suppression, HBV curation or suppression, completion of TB treatment regimen among people with SUD. The included studies were assessed qualitatively.Results: Altogether, 1640 studies, and references to 1135 related reviews and RCTs were considered, and only seven RCTs and three cohort studies fulfilled the inclusion criteria. We identified nine integrated care models. Two studies, one RCT and one cohort study, showed a significant effect of their integrated models. The RCT evaluated psychosocial treatment, opioid agonist treatment (OAT) and directly observed TB treatment, and found a significant increase in TB treatment completions among intervention group compared to control group (60% versus 13%, p < 0.01). The cohort study including OAT and TB treatments had an effect on TB treatment completion in hospitalized patients (89% versus 73%, p = 0.03). Eight out of ten studies showed no significant effects of their integrated care models on defined outcomes. One of which having included 363 participants in a RCT showed no effect on SVR compared to the control group when the results adjusted for active substance use and alcohol dependence in a post-hoc analysis (11% versus 7%, p = 0.49).Conclusions: The findings indicate uncertainty on the effects of integrated care models' on treatment for severe infectious diseases among people with SUD. Some studies point toward that integrated models could improve care of people with SUD, yet high-quality studies and preferably, sufficiently sized clinical trials are needed to conclude on the degree of impact. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) replicates non-cytopathically in the hepatocytes and HBV-related diseases are caused by immune-mediated inflammatory events. This study aimed to identify the relationship between clinical-virological characteristics and immunity in untreated chronic hepatitis B (CHB) patients.Methods: A total of 209 CHB patients were categorized into immune tolerant (IT, n = 17), inactive carrier (IC, n = 20), immune active (IA, n = 120), and gray zone (GZ, n = 72) phases. The quantitative hepatitis B surface antigen (qHBsAg), hepatitis B e antigen (HBeAg), anti-HBeAg (HBeAb), HBV genotype, viral mutant and frequencies of interleukin (IL)-4, IL-17, IL-10 and interferon-gamma (IFN-γ) produced by CD4+ and CD8+ T cells were tested. We also correlated these cytokines with clinical-virological characteristics using a linear regression model.Results: CD8+ T cells frequency were significantly decreased in IT patients. Levels of CD4+ T cells IL-4+ or IL-10+ were strongly negatively associated with qHBsAg titers. The frequency of IFN-γ produced by CD4+ and CD8+ T cells showed significant positive association with age and alanine aminotransferase (ALT) level, while that had negative association with qHBsAg titers. Additionally, the ratios of mutations in the HBV precore (PC) stop codon and basal core promoter (BCP) and the combined mutations were 32.5, 27.2, and 11.3%, respectively. The frequency of CD4+ T cells IL-17+ was higher in patients with a PC mutation than that in patients carrying a wild-type sequence. Finally, little associations among T cell derived IL-4, IL-10, IL-17, and IFN-γ was observed in the current untreated CHB cohort.Conclusions: Several components of the immune system were correlated with HBV factors that influence an inflammatory process during CHB. Of particular relevance are the significant associations of between CD4+ T cells IL-4+ and qHBsAg level, and between CD4+ T cells IL-17+ and the presence of a mutation in PC. [ABSTRACT FROM AUTHOR]

Background: The relationship between chronic hepatitis B virus (HBV) infection with gestational diabetes mellitus (GDM) remains unclear. This study aimed to identify the association between maternal HBsAg-positive status and GDM.Methods: A retrospective cohort study was performed on the pregnant women who delivered from June 2012 to May 2016 at Wuhan Medical Care Center for Women and Children, Wuhan, China. We compared the incidence of GDM between HBsAg-positive pregnant women and HBsAg-negative controls. A multivariate regression model was used to measure the independent association between maternal HBsAg carrier and the risk of developing GDM.Results: In total, 964 HBsAg-positive pregnant women and 964 HBsAg-negative women were included into the study. We observed maternal HBsAg carrier (OR 1.47, 95% CI 1.06-2.03), age (OR 1.05, 95% CI 1.00-1.10) and family history of diabetes (OR 3.97, 95% CI 2.05-7.67) had an independent risk for GDM in multivariable logistical regression model. However, no significant association was found between HBeAg carrier status, other HBV markers or viral load in pregnancy and the incidence of GDM.Conclusions: Our results indicated that maternal HBsAg carriage is an independent risk factor for GDM, but viral activity indicated by HBeAg status and viral load is not the main reason for this phenomenon. Further studies are warranted to clarify the possible mechanisms behind such association of HBV infection and the additional risk of GDM. [ABSTRACT FROM AUTHOR]

Background: For patients with chronic hepatitis B and cirrhosis in less developed western regions in China, due to constraints of local economic conditions, the choice of treatment measures is often limited. However if patients recieved valid management and effective treatment, they were able to maintain their health and benign prognosis.Case Presentation: This study narrates the long-term treatment and careful follow-up of a patient with chronic hepatitis B and cirrhosis in a less developed western region in China, and analyzes the prognosis of the disease and countermeasures.Conclusions: This would partly reflect the development of antiviral therapy for chronic hepatitis B and multidisciplinary comprehensive treatment for cirrhosis-related complications in remote region with limited resources in the past 20 years. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) and chronic Hepatitis B virus (HBV) infection are common in China. Fist-line anti-TB medications often produce drug-induced liver injury (DILI). This study sought to investigate whether TB patients with chronic HBV co-infection are more susceptible to liver failure and poor outcomes during anti-TB treatment.Methods: Eighty-four TB patients developed DILI during anti-TB treatment and were enrolled, including 58 with chronic HBV co-infection (TB-HBV group) and 26 with TB mono-infection (TB group). Clinical data and demographic characteristics were reviewed. The severity of DILI and incidences of liver failure and death were compared. Risk factors of clinical outcomes were defined.Results: The patterns of DILI were similar in both groups. Compared with patients in the TB group, patients in the TB-HBV group who did not receive anti-HBV therapy before anti-TB treatment were more susceptible to Grade-4 severity of DILI (36.2% vs. 7.7%, P = 0.005), liver failure (67.2% vs. 38.5%, P = 0.013) and poor outcomes (37.9% vs. 7.7%, P = 0.005). Age > 50 years (48.1% vs. 22.6%, P = 0.049), cirrhosis (50.0% vs. 15.4%, P = 0.046) and total bilirubin > 20 mg/dl (51.6% vs. 14.8%, P = 0.005) were independent risk factors for the rate of death in the TB-HBV group, and HBV DNA > 20,000 IU/ml had borderline significance (44.1% vs. 20.8%, P = 0.081). In the TB-HBV group, nucleos(t)ide analogues as rescue therapy were not able to reduce short-term death (33.3% vs. 36.8%, P = 0.659) once liver failure had occurred.Conclusions: Patients on anti-TB therapy with chronic HBV co-infection are more susceptible to developing liver failure and having poor outcomes during anti-TB treatment. Regular monitoring of liver function and HBV DNA level is mandatory. Anti-HBV treatment should be considered in those with high viral levels before anti-TB treatment. [ABSTRACT FROM AUTHOR]

Background: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe.Methods: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence.Results: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32-3.10],P = 0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties.Conclusions: Immune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence. [ABSTRACT FROM AUTHOR]