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Background: The provincial-level sero-survey was launched to learn the updated seroprevalence of hepatitis B virus (HBV) infection in the general population aged 1–69 years in Chongqing and to assess the risk factors for HBV infection to effectively screen persons with chronic hepatitis B (CHB). Methods: A total of 1828 individuals aged 1–69 years were investigated, and hepatitis B surface antigen (HBsAg), antibody to HBsAg (HBsAb), and antibody to B core antigen (HBcAb) were detected. Logistic regression and three machine learning (ML) algorithms, including random forest (RF), support vector machine (SVM), and stochastic gradient boosting (SGB), were developed for analysis. Results: The HBsAg prevalence of the total population was 3.83%, and among persons aged 1–14 years and 15–69 years, it was 0.24% and 4.89%, respectively. A large figure of 95.18% (770/809) of adults was unaware of their occult HBV infection. Age, region, and immunization history were found to be statistically associated with HBcAb prevalence with a logistic regression model. The prediction accuracies were 0.717, 0.727, and 0.725 for the proposed RF, SVM, and SGB models, respectively. Conclusions: The logistic regression integrated with ML models could helpfully screen the risk factors for HBV infection and identify high-risk populations with CHB. [ABSTRACT FROM AUTHOR]

Background: Aberrant Wnt5a expression contributes to immunity, inflammation and tissue damage. However, it remains unknown whether Wnt5a is associated with liver injury in chronic hepatitis B virus (HBV) infection. We aimed to explore the potential role of Wnt5a expression in liver injury caused by chronic HBV infection. Methods: Wnt5a mRNA levels in peripheral blood mononuclear cells (PBMCs) were analyzed in 31 acute-on-chronic hepatitis B liver failure (ACHBLF) patients, 82 chronic hepatitis B (CHB) patients, and 20 healthy controls using quantitative real-time polymerase chain reaction. Intrahepatic Wnt5a protein expression from 32 chronic HBV infection patients and 6 normal controls was evaluated by immunohistochemical staining. Results: Wnt5a mRNA expression was increased in CHB patients and ACHBLF patients compared to healthy controls and correlated positively with liver injury markers. Additionally, there was a significant correlation between Wnt5a mRNA expression and HBV DNA load in all patients and CHB patients but not in ACHBLF patients. Furthermore, intrahepatic Wnt5a protein expression was elevated in chronic HBV infection patients compared to that in normal controls. Moreover, chronic HBV infection patients with higher hepatic inflammatory grades had increased intrahepatic Wnt5a protein expression compared with lower hepatic inflammatory grades. In addition, the cut-off value of 12.59 for Wnt5a mRNA level was a strong indicator in predicting ACHBLF in CHB patients. Conclusions: We found that Wnt5a expression was associated with liver injury in chronic HBV infection patients. Wnt5a might be involved in exacerbation of chronic HBV infection. [ABSTRACT FROM AUTHOR]

Background: Despite the availability of an effective vaccine, chronic hepatitis B virus (HBV) infections remain a major cause of liver cirrhosis and hepatocellular carcinoma. HBV burden in pregnancy, risk factors and the timing of mother to child transmission remain poorly described especially during this era of lifelong use of Tenofovir/Lamivudine/Efavirenz as firstline for HIV treatment. We aimed to determine the burden of HBV in pregnancy and infants receiving their first dose of HBV vaccine 6 weeks after birth in a high HIV-prevalence setting. Methods: Pregnant women ≥ 20 weeks' gestational age were enrolled and followed up as mother-infant dyads from delivery, 6, 24 and 96 weeks after birth. HBV surface antigen (HBsAg) was tested (fresh plasma, immunochromatography) in pregnancy. Women testing HBsAg-seropositive were further evaluated for other four HBV-biomarkers. Maternally HBV exposed babies were tested for HBsAg from birth and HBs-antibodies from 6 months of age. Maternal-infant factors were tested in univariable and multivariable analyses for predictors of HBsAg-seropositivity. Results: Six hundred HIV-uninfected and 608 HIV-infected women on Tenofovir/Lamivudine/Efavirenz-regimen with median (interquartile range) 350: (87–1477) days of therapy use were enrolled. The overall HBsAg-seroprevalence was 32/1208: 2.65%, 95% confidence interval (CI) [1.74, 3.55]; being 7/600: 1.17%, 95% CI [0.37, 1.97] and 25/608: 4.11%, 95% CI [2.52, 5.68] in HBsAg-monoinfected and HBsAg/HIV-coinfected respectively, disproportionately detected in 31/32: 96.9%, 95% CI [90.8, 100] women presumably HBV-unvaccinated in infancy. HBV exposed babies tended to be born prematurely (< 37 weeks); 15.2% versus 9.9% in the HBV-unexposed, p = 0.009. In multivariate logistic regression-models with variable elimination, HIV-infection and reported tooth extractions predicted antenatal HBsAg-seropositivity; odds ratios (CI): 3.85 (1.61–10.7) and 2.46 (1.07–5.34), respectively. None of the exposed infants were HBsAg-seropositive neither before nor after 6 weeks of age. No HBs-antibodies were detected in 23.3% of HBsAg-exposed infants at two years despite having successfully completed the HBV vaccination schedule. Conclusion: Low and moderate HBV endemics were observed in HIV-uninfected and HIV-infected pregnant women, respectively. This underscores the need to routinely screen for HBV in pregnancy, especially the HIV-infected attending antenatal-care. Being HIV-infected and reported tooth extractions were independent risk factors for maternal HBsAg-seropositivity. Vertical and child horizontal transmissions were both absent, probably due to ~ the 50% frequency of antenatal anti-HBe-antibodies observed. Of concern was the absence of anti-HBs-antibodies in 23.3% of fully vaccinated/maternally HBV-exposed infants by two years. Absence of molecular diagnosis may have underestimated HBV burden. Trial registration: www.clinicaltrials.gov, trial registration number: NCT04087239. [ABSTRACT FROM AUTHOR]

Background: Chronic HBV infection is always accompanied by differences in the balance between regulatory T cells (Tregs) and T-helper 17 (Th17) cells in infection phases. IL-21 plays an important role in the progression of chronic HBV infection. Thus, the aim of our study was to investigate the role of the regulatory function of IL-21 in maintaining the balance between Tregs and Th17 cells in chronic HBV infection. Methods: Twenty-five chronic HBV-infected patients in the immune-tolerant (IT) phase and 23 chronic hepatitis B (CHB) patients were recruited in this study. Cytokines production was measured by ELISA. The mRNA expression levels were determined by qPCR. CD4+T cells were stimulated with or without IL-21. Tregs and Th17 cells were measured by flow cytometry. pSTAT3 and STAT3 expression was assessed by Western blotting. Results: The concentration of IL-21 in the serum of CHB were significantly higher than that in the serum from IT patients, and IL-21 and IL-21R levels in the PBMCs from CHB were higher than those from IT patients. IL-21 promoted Th17 cells differentiation and function but inhibited Treg cells differentiation and function by activating STAT3 signaling pathways, upregulating RORγt expression, downregulating Foxp3 expression, by increasing IL-17and IL-22 secretion, and decreasing TGF-β secretion in chronic HBV infection. The proportion of Tregs and TGF-β concentrations in CHB was significantly lower than that in IT patients. Furthermore, the percentage of Th17 cells and the IL-17 concentration in CHB was markedly higher than that in IT patients, causing a reduction in the Tregs/Th17 ratio in CHB patients. Conclusions: Our results suggest that IL-21 may contribute to inflammation in chronic HBV infection by modulating the balance between Treg and Th17 cells. [ABSTRACT FROM AUTHOR]

Background: The geographical distribution of hepatitis B virus (HBV) and hepatitis D virus (HDV) genotypes is uneven and has its own clinical and organizational implications for health systems. Despite the introduction of vaccination and successful antiviral therapy the prevalence of chronic hepatitis B (with or without delta agent) increased over the past 5 years. This study aimed for the first time to investigate the molecular epidemiology of HBV and HDV in Kazakhstan. Methods: Total 834 chronic hepatitis B (with or without delta agent) patients were included to the study from November 2017 to June 2019. The material was collected from the regional hepatological сenters from 13 cities of Kazakhstan. Genotyping of HBV/HDV isolates was carried out using phylogenetic analysis of null-binary sequences of Kazakhstani isolates, in comparison with the reference sequences. Nucleotide sequence alignment was performed using the ClustalW algorithm, the "neighbor-joining" method was used for the construction of phylogenetic trees and subsequent analysis. Results: Overall 341 samples were PCR-positive and genotyped for HBV. Comparison and phylogenetic analysis of nucleotide sequences of HBV isolates showed that they were represented by genotypes HBV-D (95.9%), HBV-A (3.5%) and HBV-C (0.6%). At the same time, the identity of the nucleotide sequences of Kazakhstani isolates were: HBV-D (95–100%); HBV-A (97.2–100%) and HBV-C (99%). 256 samples were PCR positive and genotyped for HDV, all of them belonged to genotype 1. Conclusion: This study describes for the first time the molecular epidemiology of HBV and HDV in Kazakhstan. The data obtained expand the knowledge of the global epidemiology of viruses; have potential implications for public health policy and for further clinical research on chronic hepatitis in Kazakhstan. Trial registration: ClinicalTrials.gov NCT05095181 (registered on 27/10/2021). [ABSTRACT FROM AUTHOR]

Background & aims: This study aimed to establish multivariate prediction models according to a response-guided therapy (RGT) based strategy at baseline and week 12 and 24 of follow-up to predict the functional cure for HBeAg-negative patients with chronic hepatitis B (CHB) treated with pegylated interferonα (PEG-IFNα). Methods: A total of 242 HBeAg-negative patients with CHB were treated with PEG-IFNα for 52 weeks and followed up for 24 weeks. Responses at the end of follow-up (EOF) were defined as hepatitis B surface antigen (HBsAg) loss, and patients were defined as either responders or non-responders. Results: The three most meaningful predictors were an age ≤ 40 years, alanine aminotransferase (ALT) levels ≤ 40 U/L, and HBsAg levels ≤ 100 IU/mL at baseline; ALT levels ≥ 80 U/L, anti-HBc levels ≤ 8.42 S/CO, and HBsAg levels ≤ 50 IU/mL at week 12; and ALT levels ≥ 40 U/L, anti-HBc levels ≤ 8.46 S/CO, and HBsAg levels ≤ 0.2 IU/mL at week 24. The response rates of patients with a score of 0–1 and 4–5 at baseline, week 12, and 24 were 13.5%, 7.8%, and 11.7%; and 63.6%, 68.1%, and 98.1%, respectively. At week 12, the cumulative scores were 0–2, 3–4, 5–7, and 8–10 (response rates 5.0%, 18.9%, 41.3%, and 71.4%, respectively). At week 24, the cumulative scores were 0–3, 4–6, 7–10, and 11–15 (response rates: 1.3%, 12.3%, 37.0%, and 92.5%, respectively). At baseline, patients with scores of 0–1 were slightly recommended; at week 12, patients with 0–1 or 0–2 cumulative scores were recommended to stop treatment. At week 24, patients with a score of 0–1 or a cumulative score of 0–6 were recommended to stop treatment. Conclusion: We established a multi-parameter prediction model for the functional cure of HBeAg-negative patients with CHB treated with PEG-IFNα. [ABSTRACT FROM AUTHOR]

Background: The impact of corticosteroids on patients with severe coronavirus disease 2019 (COVID-19)/chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate the association of corticosteroids on these patients.Methods: This retrospective multicenter study screened 5447 confirmed COVID-19 patients hospitalized between Jan 1, 2020 to Apr 18, 2020 in seven centers in China, where the prevalence of chronic HBV infection is moderate to high. Severe patients who had chronic HBV and acute SARS-cov-2 infection were potentially eligible. The diagnosis of chronic HBV infection was based on positive testing for hepatitis B surface antigen (HBsAg) or HBV DNA during hospitalization and a medical history of chronic HBV infection. Severe patients (meeting one of following criteria: respiratory rate > 30 breaths/min; severe respiratory distress; or SpO2 ≤ 93% on room air; or oxygen index < 300 mmHg) with COVID-19/HBV co-infection were identified. The bias of confounding variables on corticosteroids effects was minimized using multivariable logistic regression model and inverse probability of treatment weighting (IPTW) based on propensity score.Results: The prevalence of HBV co-infection in COVID-19 patients was 4.1%. There were 105 patients with severe COVID-19/HBV co-infections (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. In the multivariable analysis, corticosteroid therapy (OR, 6.32, 95% CI 1.17-34.24, P = 0.033) was identified as an independent risk factor for 28-day mortality. With IPTW analysis, corticosteroid treatment was associated with delayed SARS-CoV-2 viral RNA clearance (OR, 2.95, 95% CI 1.63-5.32, P < 0.001), increased risk of 28-day and in-hospital mortality (OR, 4.90, 95% CI 1.68-14.28, P = 0.004; OR, 5.64, 95% CI 1.95-16.30, P = 0.001, respectively), and acute liver injury (OR, 4.50, 95% CI 2.57-7.85, P < 0.001). Methylprednisolone dose per day and cumulative dose in non-survivors were significantly higher than in survivors.Conclusions: In patients with severe COVID-19/HBV co-infection, corticosteroid treatment may be associated with increased risk of 28-day and in-hospital mortality. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to analyze the liver tissue changes among the CHB patients who received treatment for at least 6 months and follow-up for at least 1 year, together with the correlation between the different disease condition and serum markers.Methods: One-hundred and eighty-five CHB patients underwent antiviral therapy for at least 6 months were enrolled. In the 12-month follow-up, ultrasonography-guided biopsy was performed. The patients were grouped based on the serum markers and pathological changes in liver tissues. Then we determined the serum markers, virological tests and Tim-3 expression among these groups.Results: Antiviral therapy significantly reduced liver inflammation indicators and serum Tim-3 level. However, the fibrosis process of liver tissue was not changed, and there are still disputes on the serum marker and hepatic lesion outcomes. Under normal liver function or negative hepatitis B e antigen (HBeAg) of CHB patients, there might be consensus between Tim-3 change and liver pathological outcome. According to the liver tissue inflammation and fibrosis conditions, Tim-3 was positively correlated with liver function indices. Besides, it was also related to fibrosis stage and inflammation grade.Conclusion: There were inconsistent changes between serum markers and liver tissue conditions after anti-viral therapy. Tim-3 expression was more suitable to indicate the changes of liver inflammatory and fibrosis response to some extent than ALT and AST. It may serve as a certain indicator to predict the CHB prognosis, which could be used as one of the monitoring indicators in liver pathological changes of chronic HBV infection, especially in monitoring liver tissue inflammation. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to analyze the liver tissue changes among the CHB patients who received treatment for at least 6 months and follow-up for at least 1 year, together with the correlation between the different disease condition and serum markers. Methods: One-hundred and eighty-five CHB patients underwent antiviral therapy for at least 6 months were enrolled. In the 12-month follow-up, ultrasonography-guided biopsy was performed. The patients were grouped based on the serum markers and pathological changes in liver tissues. Then we determined the serum markers, virological tests and Tim-3 expression among these groups. Results: Antiviral therapy significantly reduced liver inflammation indicators and serum Tim-3 level. However, the fibrosis process of liver tissue was not changed, and there are still disputes on the serum marker and hepatic lesion outcomes. Under normal liver function or negative hepatitis B e antigen (HBeAg) of CHB patients, there might be consensus between Tim-3 change and liver pathological outcome. According to the liver tissue inflammation and fibrosis conditions, Tim-3 was positively correlated with liver function indices. Besides, it was also related to fibrosis stage and inflammation grade. Conclusion: There were inconsistent changes between serum markers and liver tissue conditions after anti-viral therapy. Tim-3 expression was more suitable to indicate the changes of liver inflammatory and fibrosis response to some extent than ALT and AST. It may serve as a certain indicator to predict the CHB prognosis, which could be used as one of the monitoring indicators in liver pathological changes of chronic HBV infection, especially in monitoring liver tissue inflammation. [ABSTRACT FROM AUTHOR]

Background: The rates of hepatitis B virus (HBV) infection in rheumatoid arthritis (RA) patients are controversial when considering the reported outcomes. It was speculated that HBV infection status was altered after RA, and variations inn HBV infection rates became apparent.Methods: To compare the positive proportions of hepatitis B e antigen (HBeAg) and HBV DNA, a retrospective case-control study was performed between 27 chronic hepatitis B (CHB) patients with RA and 108 age- and gender-matched CHB patients. In addition, the positivity rates of hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) were surveyed among the 892 RA patients.Results: Compared to CHB patients, CHB patients with RA exhibited lower rates of HBeAg positivity (11.1% vs. 35.2%, P = 0.003), HBV DNA positivity (37.0% vs. 63.9%, P = 0.007) and ALT elevation (11.1% vs. 35.2%, P = 0.024). In the 892 RA patients, the prevalence of HBsAg (3.0%) was lower than that reported in the Chinese national data (7.2%), whereas the anti-HBc positivity rate of 44.6% was higher than that of 34.1%.Conclusion: HBV infection status was altered after suffering from RA. Compared to the matched CHB patients, low positive proportions of HBeAg and HBV DNA were observed for CHB patients with RA. [ABSTRACT FROM AUTHOR]

Background: This study was designed to evaluate the prevalence, genotypic patterns, and predominant mutations of hepatitis B virus (HBV) infection among diabetic patients.Methods: Serum samples were obtained from 733 patients with type 2 diabetes mellitus and 782 non-diabetic controls. The presence of HBsAg and HBcAb was determined by ELISA. Nested PCR, targeting S and pre-core regions of the HBV genome, followed by sequencing was carried out to determine HBV genotypes and predominant mutations in the S, basal core promoter (BCP), and pre-core regions of the HBV genome.Results: Of 733 diabetic patients, 94 cases (12.82%) were positive for HBcAb, 28 cases (3.82%) were positive for HBsAg, and 19 cases (2.59%) had HBV-DNA with genotype D, sub-genotype D1/D3 and subtype ayw2. An occult HBV infection was found in one of the HBV DNA-positive samples, which was positive for HBcAb but negative for HBsAg. P120T/G145R, G1896A/G1899A, and A1762T/G1764T were the most frequent point substitution mutations detected in the S, pre-core, and BCP regions of the HBV genome, respectively. P120T and G145R mutations were associated with low levels or undetectable levels of HBsAg in serum. Therefore, routine tests based on HBsAg detection cannot detect HBsAg-negative infected patients.Conclusions: Relatively high prevalence of HBV infection was found in diabetic patients, while all of the HBV-infected patients were unaware of their infection. Therefore, screening for HBV infection should be included in the management program of diabetes for timely diagnosis and treatment of infected but asymptomatic patients. [ABSTRACT FROM AUTHOR]

Background: There remain gaps in quantifying mortality risk among individuals co-infected with chronic hepatitis B (HBV) and human immunodeficiency virus (HIV) in sub-Saharan African contexts. Among a cohort of HIV-positive individuals in Rwanda, we estimate the difference in time-to mortality between HBV-positive (HIV/HBV co-infected) and HBV-negative (HIV mono-infected) individuals. Methods: Using a dataset of HIV-infected adults screened for hepatitis B surface antigen (HBsAg) from January to June 2016 in Rwanda, we performed time-to-event analysis from the date of HBsAg results until death or end of study (31 December 2019). We used the Kaplan–Meier method to estimate probability of survival over time and Cox proportional hazard models to adjust for other factors associated with mortality. Results: Of 21,105 available entries, 18,459 (87.5%) met the inclusion criteria. Mean age was 42.3 years (SD = 11.4) and 394 (2.1%) died during follow-up (mortality rate = 45.7 per 100,000 person-months, 95% confidence interval (CI) 41.4–50.4) Mortality rate ratio for co-infection was 1.7, 95% CI 1.1–2.6, however, Cox regression analysis did not show any association with mortality between compared groups. The adjusted analysis of covariates stratified by co-infection status showed that males, residing outside of the capital Kigali, drinking alcohol, WHO-HIV-clinical stage 3 and 4 were associated with increased mortality in this HIV cohort. Conclusions: HBV infection does not significantly influence mortality among HIV-infected individuals in Rwanda. The current cohort is likely to have survived a period of high-risk exposure to HBV and HIV mortality and limited health care until their diagnosis. [ABSTRACT FROM AUTHOR]

Background: There remain gaps in quantifying mortality risk among individuals co-infected with chronic hepatitis B (HBV) and human immunodeficiency virus (HIV) in sub-Saharan African contexts. Among a cohort of HIV-positive individuals in Rwanda, we estimate the difference in time-to mortality between HBV-positive (HIV/HBV co-infected) and HBV-negative (HIV mono-infected) individuals.Methods: Using a dataset of HIV-infected adults screened for hepatitis B surface antigen (HBsAg) from January to June 2016 in Rwanda, we performed time-to-event analysis from the date of HBsAg results until death or end of study (31 December 2019). We used the Kaplan-Meier method to estimate probability of survival over time and Cox proportional hazard models to adjust for other factors associated with mortality.Results: Of 21,105 available entries, 18,459 (87.5%) met the inclusion criteria. Mean age was 42.3 years (SD = 11.4) and 394 (2.1%) died during follow-up (mortality rate = 45.7 per 100,000 person-months, 95% confidence interval (CI) 41.4-50.4) Mortality rate ratio for co-infection was 1.7, 95% CI 1.1-2.6, however, Cox regression analysis did not show any association with mortality between compared groups. The adjusted analysis of covariates stratified by co-infection status showed that males, residing outside of the capital Kigali, drinking alcohol, WHO-HIV-clinical stage 3 and 4 were associated with increased mortality in this HIV cohort.Conclusions: HBV infection does not significantly influence mortality among HIV-infected individuals in Rwanda. The current cohort is likely to have survived a period of high-risk exposure to HBV and HIV mortality and limited health care until their diagnosis. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) is detected in extrahepatic tissues of individuals with HBV infection. Whether nails and hair contain HBV has been unknown.Methods: We examined two patient groups: those with chronic HBV infection alone (n = 71), and those with both chronic HBV and hepatitis delta virus (HDV) infections (n = 15). HBV DNA in the patients' fingernails and hair were measured by real-time PCR. Hepatitis B surface antigen (HBsAg) of fingernails was evaluated by an enzyme immunoassay. HDV RNA in fingernails was measured by real-time PCR. Immunochemical staining was performed on nails. We used chimeric mice with humanized livers to evaluate the infectivity of nails.Results: Of the 71 pairs of HBV-alone nail and hair samples, 70 (99%) nail and 60 (85%) hair samples were positive for β-actin DNA. Of those 70 nail samples, 65 (93%) were HBV DNA-positive. Of the 60 hair samples, 49 (82%) were HBV DNA-positive. The serum HBV DNA level of the nail HBV DNA-positive patients was significantly higher than that of the nail HBV DNA-negative patients (p < 0.001). The hair HBV DNA-positive patients' serum HBV DNA level was significantly higher compared to the hair HBV DNA-negative patients (p < 0.001). The nail HBV DNA level was significantly higher than the hair HBV DNA level (p < 0.001). The nails and hair HBV DNA levels were correlated (r = 0.325, p < 0.05). A phylogenetic tree analysis of the complete genome sequence of HBV isolated from nails and hair identified the infection source. Of the 64 nail samples, 38 (59%) were HBsAg-positive. All 15 pairs of chronic HBV/HDV infection nail and hair samples were β-actin DNA-positive. However, nail HBV DNA was detected in two patients (13%). None of the 15 patients were positive for hair HBV DNA. Nail HDV RNA was detected in three patients (20%). Of the 15 patients, eight (53%) were nail HBsAg-positive. HBsAg and hepatitis delta (HD) antigen were detected in the nails by immunochemical staining. Chimeric mice were not infected with PBS containing HBsAg and HBV DNA elucidated from nails.Conclusions: Nails and hair were the reservoir of HBV DNA. Moreover, nails can contain HBsAg, HDV RNA, and HD antigen. [ABSTRACT FROM AUTHOR]

Backgrounds: Hepatitis B virus (HBV) biomarkers reflect the status of HBV infection; however, their role in patients with chronic hepatitis B and C (HBV/HCV) coinfection remains unknown. This study evaluated the characteristics of HBV biomarkers in patients with chronic HBV/HCV coinfection.Methods: One hundred untreated HBV/HCV coinfected patients were enrolled. Active viral infection was defined as viral load above 2000 U/L and 15 U/L for HBV and HCV, respectively. Blood samples were analyzed for HBV biomarkers, including hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), HBV DNA, and HBV pregenomic RNA (HBV pgRNA). The impact of HCV viremia was also studied.Results: A total of 15 patients were HBV-inactive/HCV-inactive, 63 patients were HBV-inactive/HCV-active, 14 patients were HBV-active/HCV-inactive and 8 patients were HBV-active/HCV-active. A total of 71 (71%) patients were active HCV and 22 (22%) were active HBV. HBsAg, HBcrAg, and HBV DNA correlated with each other (P < 0.001). HBV pgRNA displayed no correlations with HBV DNA, HBsAg, or HBcrAg. Patients with HCV viremia had significantly lower HBV DNA, HBsAg, and HBcrAg levels as well as higher HBV pgRNA levels and lower HBV DNA:pgRNA ratio than those without viremia (HBV DNA, P < 0.001; HBsAg, P = 0.015; HBcrAg, P = 0.006; HBV pgRNA, P = 0.073; and HBV DNA:pgRNA ratio, P < 0.001).Conclusions: In patients coinfected with HBV and HCV, HBsAg, HBcrAg, and HBV DNA significantly correlated with each other. HBV and HCV coinfected patients with HCV viremia have lower HBV DNA, HBsAg, HBcrAg, and HBV DNA:pgRNA ratio as well as higher HBV pgRNA levels. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial myopathy caused by the long-term use of nucleos(t)ide analogue in patients with chronic hepatitis B (CHB) is mostly characterized by myasthenia and myalgia. Cases with respiratory failure as the prominent manifestation and multisystem symptoms have not been reported.Case Report: We report a case of mitochondrial myopathy associated with the long-term use of entecavir for CHB. The patient was a 54-year-old male who was treated with entecavir for 9 years. During the treatment, hepatitis B virus (HBV) DNA was negative and liver function was normal. However, generalized fatigue, poor appetite, dysosmia and other discomforts gradually presented starting at the 5th year of treatment, and respiratory failure was the prominent manifestation in the later stage of disease progression. The diagnosis was based on histopathology examination. The dysosmia, hypoxemia and digestive tract symptoms were gradually improved after withdrawal of entecavir.Discussion: Mitochondrial myopathy is a rare side effect of entecavir and can be diagnosed by muscle biopsy. Although the incidence is extremely low, but the severe cases can lead to respiratory failure. We should receive adequate attention in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the diagnostic value of the single or combined applications of transient elastography (TE) and multivariate indicators with biopsy for the detection of liver fibrosis in children caused by chronic hepatitis B (CHB).Methods: This study included 148 CHB children treated at Hunan Children's Hospital from January 1st 2015 to December 31st 2018, aged from 0.83 to 14.58 years old. All patients underwent liver biopsy (LB), of which 43 patients underwent TE. Multiple clinical data, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), Platelet (PLT), and HBV-deoxyribonucleic acid (HBV DNA) of all patients were collected. The diagnostic values for CHB of TE and its combinations with these indicators were measured. The patients were classified in two ways: no hepatic fibrosis group (F0) versus fibrosis group (F ≥ 1), and no significant hepatic fibrosis group (F < 2) versus significant hepatic fibrosis group (F ≥ 2). The statistical assessment was performed between groups within each classification to compare the diagnostic value of different parameters.Results: The operating characteristic area under curve (AUC) of liver fibrosis diagnosed by liver stiffness measurement (LSM) which obtained by TE, AST-to-PLT ratio index (APRI), and fibrosis-4 index (FIB-4) were 0.740, 0.701, and 0.651, while the corresponding cut-off values were 5.9 kPa, 0.50, and 0.10, respectively. The AUC of significant liver fibrosis diagnosed by LSM, APRI and FIB-4 were 0.849, 0.701, and 0.509, while the corresponding cut-off values were 8.4 kPa, 0.76, and 0.08, respectively. While with the combinations of LSM and APRI, LSM and FIB-4, LSM and APRI and FIB-4, APRI and FIB-4, the AUC of significant liver fibrosis were 0.866, 0.855, 0.869, and 0.684, respectively. The AUC of significant liver fibrosis diagnosed by the LSM was significantly higher than APRI and FIB-4.Conclusions: The diagnostic value of transient elastography was better than that of APRI and FIB-4 for CHB children with significant liver fibrosis. In addition, TE also has relatively high application values on the diagnosis of patients with different degrees of liver fibrosis caused by CHB. [ABSTRACT FROM AUTHOR]

Background: In people living with HIV/AIDS (PLWHA), initiation of antiretroviral therapy (ART) leads to sustained effective suppression of viral replication and increasing CD4 + T cell count. However, a fraction of ART-treated patients still fail to reach adequate CD4 + T cell number despite a suppressed viral load (VL), and this phenomenon is defined as immunovirological discordance (IVD). In Africa, several studies have reported immunovirological outcomes of antiretroviral therapy, but little is known about IVD occurrence in Female sex workers (FSW). This study aimed to assess the prevalence of IVD and associated factors among a cohort of HIV infected FSW in Burkina Faso.Methods: We conducted a cohort study from December 2003 to October 2016. Immunovirological discordance was defined as CD4 + T cell gain < 100 cells/µL despite a suppressed VL (VL < 1000 copies/mL) 12 months after ART initiation. The CD4 + T cells were counted using BD FACSCount™ System and point of care Pima™ CD4 + Analyzer. HIV-1 RNA was quantified by real-time polymerase-chain-reaction assay with the use of the ABI 7000 system. We conducted a logistic regression to identify factors associated with discordant responses.Results: Among the 123 HIV-1 infected FSW having at least 12 months follow-up on ART, 105 (85.4%) achieved HIV-1 RNA suppression. Among the latter 25 gained less than 100 CD4 + T cells within 12 months follow-up. The IVD rate was 23.8% (95%CI 16.04%-33.11%). After adjustment for age, WHO clinical stage and ART regimen including nucleoside/nucleotide reverse transcriptase inhibitors, only baseline CD4 + T cell count between 200 to 350 cells/µL (adjusted OR: 4.15; 95%CI 1.13-15.22) and 350 to 500 cells/µL (adjusted OR: 17.50; 95%CI 2.68-114.31) remain significantly associated with IVD occurrence.Conclusions: Immunovirological discordance response was common in FSW with proportions close to those observed in the general population. A diagnosis and personalized follow-up of patients who do not achieve full immune reconstitution would make it possible to avoid complications in terms of morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Fc gamma receptor IIb (FcγRIIb) is an important inhibitory receptor that plays vital roles in regulating various immune response processes and the pathogenesis of many infectious diseases. The purpose of our research was to evaluate FcγRIIb expression in serum and liver biopsy specimens from hepatitis B virus (HBV)-infected patients and to explore the association of FcγRIIb with chronic HBV infection.Methods: Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum FcγRIIb levels in 119 HBV-infected patients and 24 healthy controls. An immunohistochemical method was then employed to identify FcγRIIb expression in biopsy specimens from patients with chronic hepatitis B (CHB). The integrated optical density (IOD) value was measured to represent FcγRIIb expression levels.Results: Serum FcγRIIb levels were decreased in CHB patients compared to controls (P < 0.001). The FcγRIIb levels in the CHB patient group were remarkably lower than those in the HBV carrier group (P < 0.001). In addition, FcγRIIb levels were negatively associated with AST and ALT (r = -0.3936, P = 0.0063; r = -0.3459, P = 0.0097, respectively). The IOD values of FcγRIIb expression in the moderate and severe CHB groups were significantly lower than those in the control group (P = 0.006 and P < 0.001, respectively). The FcγRIIb level tended to be lower with pathological changes related to hepatitis. Furthermore, correlation analysis revealed that FcγRIIb had negative correlations with AST and ALT (r = -0.688, P = 0.0016; r = -0.686, P = 0.0017, respectively) but a positive association with the platelet count (r = 0.6464, P = 0.0038).Conclusions: FcγRIIb levels are significantly related to chronic HBV infection and the progression of CHB. Changes in FcγRIIb may affect the progression of liver inflammation and fibrosis in CHB patients. [ABSTRACT FROM AUTHOR]

Background: To establish a prediction of HBsAg seroconversion in children with chronic hepatitis B (CHB), so as to help clinicians to choose therapeutic strategy.Methods: A total of 63 children with HBeAg-positive CHB aged 1 to 17 years, who admitted to the fifth medical center of Chinese PLA general hospital and treated with interferon α (IFNα) 48 weeks were enrolled, the clinical data were measured. Based on the results of HBsAg seroconversion (HBsAg < 0.05 IU/mL and anti-HBsAg > 10 IU/L) at week 48, the patients were divided into HBsAg seroconversion (S) group and non-HBsAg seroconversion (NS) group. Multivariate COX regression was used to identify the impact factors associated with HBsAg seroconversion. A novel prediction index was established and the area under the receiver operating characteristic curve (AUROC) was used to assess the prediction for HBsAg seroconversion.Results: The 63 patients were divided into S group (20.6%, 13/63) and NS group (79.4%, 50/63). Univariate and multivariate analysis identified age, baseline intrahepatic cccDNA and serum HBsAg levels were independent impact factors for HBsAg seroconversion. Intrahepatic cccDNA was positively correlated with serum HBsAg (r = 0.464, p = 0.000). AUROC of HBV cccDNA was 0.83 (95% CI 0.71 to 0.95) and AUROC of baseline HBsAg was 0.77 (95% CI 0.61 to 0.92). Intrahepatic cccDNA ≤ 0.08 log10 copies/106 cell is regarded as cutoff value, the positive predictive value(PPV) and negative predictive value(NPV) for HBsAg seroconversion were 86.8% and 60.0%, respectively, with a sensitivity of 92.0% and specificity of 56.2%. HBsAg ≤ 3.68 log10 IU/mL is used as cut off value, the PPV and NPV for HBsAg seroconversion were 91.2% and 56.3%, respectively; the sensitivity and specificity was 86.0% of 69.2%, respectively. There was no statistical difference between them for predicting HBsAg seroconversion (p = 0.146).Conclusions: HBsAg seroconversion can be predicted by the baseline serum HBsAg or intrahepatic cccDNA in children with CHB. Using the index, clinicians can choose more reasonable therapeutic strategy and reduce the waste of medical resources. [ABSTRACT FROM AUTHOR]

Background: Postpartum alanine transaminase (ALT) flares occur frequently in chronic hepatitis B virus (HBV)-infected mothers with antepartum antiviral therapy (AVT). We aimed to characterize the T cell immunity in HBV-infected mothers experiencing postpartum ALT flares.Methods: Twenty HBV-infected pregnant women who received AVT at 26-28 weeks of gestation were enrolled and followed up until 15-18 weeks postpartum. Among the 20 HBV-infected pregnant women, 6 experienced postpartum ALT flare (AF mothers), while 14 did not (NAF mothers). T lymphocyte phenotypes and functions were analyzed using flow cytometry.Results: Compared to NAF mothers, the quantitative HBsAg levels in AF mothers decreased significantly at 6-8 or 15-18 weeks postpartum. Significant differences in HBeAg levels between these groups were only found at delivery. Regulatory T cell (Treg) numbers in AF mothers were lower than those of NAF mothers before AVT; however, there were no significant differences in Treg numbers at other follow-up points. Expression of other T cell phenotypes were similar between the two groups. T cells in AF mothers produced more pro-inflammatory cytokines (IFN-γ, IL-21, TNF-α, IL-2) or less anti-inflammatory cytokine (IL-10) than those in NAF mothers before, during, or after antiviral treatment. The ratio of IFN-γ to IL-10 producing by CD4+ T cells or CD8+ T cells was higher in AF mothers than that in NAF mothers during pregnancy or after delivery.Conclusions: The characteristics of T cell immunity was distinct between mothers with postpartum ALT flare and those without ALT flare from pregnancy to postpartum, which indicated that T cell immunity might get involved in postpartum ALT flare. [ABSTRACT FROM AUTHOR]

Background: Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue.Methods: Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups.Results: The rate of ETV resistance among all HBV-resistant variants increased from 6.04% in 2011 to 15.02% in 2017. TDF monotherapy and TDF combination groups showed similar rates of negative HBV DNA at 48 weeks (74.07% vs 70.00%, P > 0.05), while the ETV and ADV group showed the worst virologic response (28.00%). Also, TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function among the three groups.Conclusions: TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) remains a major global public health problem worldwide; in endemic areas, mother-to-child transmission (MTCT) of HBV is the most common transmission route. Previous studies have shown that amniocentesis for prenatal diagnosis increases the risk of MTCT of HBV among highly viraemic mothers. However, no data is available on MTCT related fetal blood sampling (FBS) because of the paucity of cases or lack of attention. We present a case series of HBV-infected women who underwent FBS with or without antiviral therapy during pregnancy and discuss the risk of MTCT after FBS.Case Presentation: Six hepatitis B surface antigen (HBsAg)-positive pregnant women who underwent FBS for prenatal diagnosis were retrospectively reviewed. Their infants were followed up with HBV serology parameters until at least 12 months of age. Among 6 cases, two hepatitis B e-antigen (HBeAg)-positive mothers had high viral loads > 7.0 log10 IU/mL, and one of them received antiviral therapy at 26+ 3 gestational weeks and achieved an anticipated level of 4.52 log10 IU/mL before FBS, while the other one did not receive any antiviral treatment. The other 4 cases were HBeAg-negative with low viral loads. Only a child born to the HBeAg-positive mother, who had no antiviral therapy with a viral load of 7.48 log10 IU/mL before FBS, was found to have MTCT with HBsAg persistently positive from birth to 12 months of age. The other 5 children were both HBsAg-negative and HBsAb-positive at the end of follow-up.Conclusions: FBS may increase the risk of MTCT of HBV in women with HBeAg-positive and high viral loads; therefore, FBS should be avoided in this high-risk population. Maternal HBV serologic testing and awareness of the potential risk of MTCT should be recommended before FBS. Antiviral therapy may be effective to decrease the risk of MTCT after FBS in highly viraemic women. [ABSTRACT FROM AUTHOR]

Background: Despite the development of a safe and efficacious hepatitis B vaccine in 1982, the hepatitis B virus (HBV) remains a public health burden in sub-Saharan Africa. Due to shared risk factors for virus acquisition, men who have sex with men (MSM) and transgender women (TGW) living with HIV are at increased risk of HBV. We estimated the prevalence of HBV and associated factors for MSM and TGW living with or without HIV in Nigeria.Methods: Since March 2013, TRUST/RV368 has recruited MSM and TGW in Abuja and Lagos, Nigeria using respondent driven sampling. Participants with HIV diagnosis, enrollment as of June 2015, and available plasma were selected for a cross-sectional study and retrospectively tested for hepatitis B surface antigen and HBV DNA. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with prevalent HBV infection.Results: A total of 717 MSM and TGW had a median age of 25 years (interquartile range [IQR]: 21-27), 5% self-reported HBV vaccination, 61% were living with HIV, 10% had prevalent HBV infection and 6% were HIV-HBV co-infected. HIV mono-infected as compared to HIV-HBV co-infected had a higher median CD4 T cell count [425 (IQR: 284-541) vs. 345 (IQR: 164-363) cells/mm3, p = 0.03] and a lower median HIV RNA viral load [4.2 (IQR: 2.3-4.9) vs. 4.7 (IQR: 3.9-5.4) log10copies/mL, p < 0.01]. The only factor independently associated with HBV was self-report of condomless sex at last anal intercourse (OR: 2.2, 95% CI: 1.3, 3.6). HIV infection was not independently associated with HBV (OR: 1.0, 95% CI: 0.7-1.6).Conclusion: HBV prevalence was moderately high but did not differ by HIV in this cohort of MSM and TGW. Recent condomless sex was associated with elevated HBV risk, reinforcing the need to increase communication and education on condom use among key populations in Nigeria. Evaluating use of concurrent HIV antiretroviral therapy with anti-HBV activity may confirm the attenuated HBV prevalence for those living with HIV. [ABSTRACT FROM AUTHOR]

Background: Current clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients.Methods: We studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018. We examined TDF treatment (vs. untreated) as the main exposure, with HBV DNA viral load (VL), ALT, elastography scores and eGFR as the main outcomes, using paired tests and mixed effects model for longitudinal measurements. Additionally, decline of eGFR during follow-up was quantified within individuals by thresholds based on clinical guidelines. Baseline was defined as treatment initiation for TDF group and the beginning of clinical follow-up for untreated group respectively.Results: We included 206 adults (60 on TDF, 146 untreated), with a median ± IQR follow-up duration of 3.3 ± 2.8 years. The TDF group was significantly older (median age 39 vs. 35 years, p = 0.004) and more likely to be male (63% vs. 47%, p = 0.04) compared to the untreated group. Baseline difference between TDF and untreated groups reflected treatment eligibility criteria. As expected, VL and ALT declined significantly over time in TDF-treated patients. Elastography scores normalised during treatment in the TDF group reflecting regression of inflammation and/or fibrosis. However, 6/81 (7.4%) of untreated patients had a progression of fibrosis stage from F0-F1 to F2 or F3. There was no evidence of difference in rates or incidence of renal impairment during follow-up in the TDF vs. untreated group.Conclusions: Risk of liver inflammation and fibrosis may be raised in untreated patients compared to those receiving TDF, and TDF may benefit a larger percentage of the CHB population. [ABSTRACT FROM AUTHOR]

Background& Aims: There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF.Methods: Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response.Results: Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported.Conclusions: TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF.Trial Registration: This study is ongoing and is registered with ClinicalTrials.gov , NCT03640728 (05/02/2019). [ABSTRACT FROM AUTHOR]

Background: People living with human immunodeficiency virus (HIV) with immuno-virological discordant responses are at an increased risk to develop acquired immunodeficiency syndrome (AIDS) and severe non AIDS events which are risk factors for death. This study was aimed to assess prevalence of immuno- virological discordant responses and associated risk factors among highly active antiretroviral therapy (HAART) users in Tigray, Northern Ethiopia.Methods: A cross sectional study was conducted from September to December 30, 2016 on 260 people living with HIV who started first line HAART from January 2008 to March 2016 at Mekelle hospital and Ayder comprehensive specialized hospital. Baseline and follow-up clinical data and CD4+ result were collected from patient charts. Besides, socio-demographic data and blood samples for CD4 + count and viral load measurement were collected during data collection period. Fisher's exact test, bivariate and multivariate logistic regressions were used for data analysis. P-value < 0.05 with 95% CI was considered as statistically significant.Result: Among the 260 study participants, 8.80% (95% Confidence Interval (CI) =8.77-8.84%) and 2.70% (95% CI = 2.68-2.72%) had virological and immunological discordant responses, respectively with an overall immuno-virological discordance response of 11.50% (95% CI = 11.46-11.54%). The median age of the study participants at HAART initiation was 35 (IQR: 28-44 years). More than half (58.1%) of the study participants were females. Age at or below 35 years old at HAART initiation (AOR ((95% CI) = 4.25(1.48-12.23), p = 0.007)), male gender ((Adjusted Odds Ratio (AOR) (95% CI) =1.71(1.13-1.10), p = 0.029)), type of regimen given ((AOR(95% CI) = 0.30 (0.10-0.88), p = 0.028)) and good treatment adherence ((AOR (95% CI) = 0.12 (0.030-0.0.48), p = 0.003)) were associated risk factors for virological discordant response. Likewise, immunological discordant response was associated with tuberculosis co-infections (p = 0.016), hepatitis B virus co-infections (p = 0.05) and low CD4+ count (≤100 cells/μl) at baseline (p = 0.026).Conclusions: Over all, immuno-virological discordance response was 11.5% in the study area. Males, low baseline CD4+ count, poor/fair treatment adherence, and TB and HBV co-infections were significantly associated with higher immuno-virological discordance. We recommend that decision of patient treatment outcome, regimen change and patient management response should be done using trends of both viral load and CD4+ count concurrently. [ABSTRACT FROM AUTHOR]

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]

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: 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]

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]

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]