BACKGROUND:The surface antigen of hepatitis B virus (HBsAg) is present on viral particles (VP) and subviral particles (SVP) and is produced from both covalently closed circular DNA (cccDNA) and HBV DNA integrated into human chromosomes. OBJECTIVE:To calculate the contribution of VP and SVP to HBsAg levels in serum, and study to what extent the source of HBsAg is cccDNA or integrated HBV DNA. METHOD:Analysis of HBV DNA and HBsAg levels from subjects with chronic HBV infection and after initiation or cessation of antiviral treatment. RESULTS:In serum samples from 800 individuals with chronic HBV infection and no antiviral treatment, the ratio between SVP and VP was > 100 million among HBe-antigen-negative subjects with low viral load. During initiation of nucleos(t)ide analogue (NA) treatment of 12 patients, the decline of HBsAg in serum was marginal or absent despite marked second phase reductions of HBV DNA, a proxy for cccDNA decline. After discontinuation of NA treatment, no increase in HBsAg levels was observed until HBV DNA had reached very high levels. CONCLUSIONS:Viral particles do not significantly contribute to HBsAg levels in serum and in HBeAg-negative patients, and the VP/SVP ratio is much lower than previously described. The contribution from cccDNA to HBsAg levels seems to be significant only when the HBV DNA serum levels are very high and reflect a cccDNA content in the liver that produces HBsAg in amounts that equal or are greater than from integrated HBV DNA.

ABSTRACT Current guidelines to prevent hepatocellular carcinoma (HCC) by chronic hepatitis B virus (HBV) infection are based on risk assessments that include age, sex, and virological and biochemical parameters. The study aim was to investigate the impact of predictive markers on long‐term outcomes. The clinical outcomes of 100 patients with chronic hepatitis B were investigated 30 years after a baseline assessment that included liver biopsy. A favourable outcome—HBsAg loss or HBeAg‐negative infection (ENI; previously termed ‘inactive carrier’)—was observed in 74% of all patients, whereas 7% developed HCC. HBsAg loss was observed in 75% of patients with genotype A, compared with 42%, 33% and 0% with genotypes D, B and C, respectively ( p < 0.0001). HCC developed in 3 patients (33%) with genotype C as compared with 3 (17%), 1 (2%) and 0 patients with genotypes B, D and A, respectively ( p < 0.0001). In multiple logistic regression analysis, both HBsAg loss and HCC were associated with HBV genotype and baseline HBV DNA level, and HCC also with histological score. The results suggest that genotyping and histological assessment may improve outcome prediction and help decisions about HCC screening, particularly in populations with HBV‐infected individuals of mixed geographic origin.

This study utilized digital PCR to quantify HBV RNA and HBV DNA within three regions of the HBV genome. Analysis of 75 serum samples from patients with chronic infection showed that HBV RNA levels were higher in core than in S and X regions (median 7.20 vs. 6.80 and 6.58 log copies/mL; p  < .0001), whereas HBV DNA levels showed an inverse gradient (7.71 vs. 7.73 and 7.77 log copies/mL, p  < .001). On average 80% of the nucleic acid was DNA by quantification in core. The core DNA/RNA ratio was associated with viral load and genotype. In individual patients, the relations between RNA levels in core, S and X were stable over time ( n  = 29; p  = .006). The results suggest that pregenomic RNA is completely reverse transcribed to minus DNA in ≈75% of the virus particles, whereas the remaining 25% contain both RNA and DNA of lengths that reflect variable progress of the polymerase.

Mother-to-child transmission (MTCT) has been the main cause of chronic hepatitis B virus (HBV) infection, particularly in East Asia. Hepatitis B immunoglobulin (HBIG) and vaccination given directly after birth effectively prevents hepatitis B surface antigen (HBsAg)-positive (overt) HBV infection, but occult hepatitis B infection (OBI) may develop despite adequate prophylaxis. The aim of this study was to investigate the long-term outcome in children born to mothers with very high HBV DNA levels with special focus on children discovered in early childhood with OBI. One-year and long-term outcome regarding overt and occult HBV infection were analysed in 66 children born to hepatitis B e antigen (HBeAg)-positive mothers, and were compared with one-year outcome in 69 children born to HBeAg-negative mothers. The children were born between 1998 and 2018. Six children born to HBeAg-positive mothers developed overt chronic HBV infection, in two cases after normal pregnancies and despite HBIG and vaccination, but never when nucleotide analogue treatment was given during pregnancy. OBI with HBV DNA detected in serum in the absence of surface antigen (HBsAg) was observed in four children at the age of 1 year. One of them was transiently HBsAg-positive at the age of 7 years. At long-term follow-up, six children had overt chronic infection, one had OBI and six had previous OBI or positive anti-HBc suggesting resolved unidentified infections. The results indicate that children born to mothers with high HBV DNA levels have approximately 10

Despite access to effective antiviral drugs and vaccines, hepatitis B virus (HBV) infection remains a major health issue worldwide. HBV is highly infectious and may cause chronic infection, progressive liver damage, hepatocellular cancer (HCC) and death. Early diagnosis, proper management and timing of treatment are crucial. The Swedish Reference group for Antiviral Treatment (RAV) here provides updated evidence-based guidelines for treatment and management of HBV infection which may be applicable also in other countries. Tenofovir alafenamide (TAF) has been introduced as a novel treatment option and new principles regarding indication and duration of treatment and characterization of hepatitis B have been gradually introduced which justifies an update of the previous guidelines from 2007. Updated guidelines on HCC surveillance in HBV-infected patients, treatment and prophylaxis for patients undergoing liver transplantation as well as management of pregnant women and children with HBV infection are also provided.

Objectives: To study the frequency of vertically acquired occult hepatitis B virus (HBV) infection (OBI). Methods: We investigated 44 children born to hepatitis B surface antigen (HBsAg) positive mothers. They received HBV vaccine directly after birth and at 2, 6 and 52 weeks of age; eight with HBeAg-positive mothers also received hepatitis B immunoglobulin (HBIG). HBV DNA was analyzed in blood collected at 6 weeks and 12 months of age, and HBV antibodies at 12 and 18 months of age. Results: HBV DNA, but not HBsAg or anti-HBc, was detected at 12 months of age in three children. The viral sequences were almost identical with HBV DNA from their mothers who all were HBeAg-positive and had received tenofovir during pregnancy. Follow-up at 5-7 years age showed that one of the three children had become seropositive for HBsAg and anti-HBc. This child and one of the other two had detectable HBV DNA at the follow-up, with whole genome sequences identical to those in HBV from their mothers. Conclusions: Mothers-to-child transmission of HBV can, despite adequate prophylaxis, lead to OBI which may later develop into overt HBV infection. Whether such infections are of clinical importance needs to be further investigated. (C) 2019 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

BACKGROUND & AIMS:Quantification of hepatitis B surface antigen (HBsAg) has been proposed as a useful diagnostic marker for clinical staging (identification of inactive carrier state) and prognosis of chronic hepatitis B virus (HBV) infection. The aim of this study was to investigate the correlation between HBsAg levels in serum and histological liver damage in patients with chronic infection. METHODS:HBsAg levels in serum (by Abbott Architect) were related to HBV DNA, ALT and histological score (n=160) and covalently closed circular DNA (cccDNA) (n=84). RESULTS:HBsAg levels correlated with cccDNA, serum HBV DNA, ALT and high inflammation scores (P<0.001). Among HBeAg-negative patients, an HBsAg level below 3.0 log10 IU/ml identified minimal liver damage (normal ALT and mild inflammation) with a predictive value of 92% (alone) or 96% (in combination with HBV DNA<4.0 log10 copies/ml), whereas an HBsAg level above 3.5 log10 IU/ml identified severe inflammation with a predictive value of 16% (alone) or 33% (in combination with HBV DNA>5.0 log10 copies/ml). CONCLUSIONS:HBsAg levels reflect clinical stage and liver disease, and a combined quantification of HBsAg and HBV DNA may improve clinical staging.

Background: The importance of hepatitis B virus (HBV) genotype on the clinical course of chronic HBV infection is not yet clarified.Objectives: To investigate genotype impact on long- term virological outcome of chronic HBV infection.Study design: HBsAg, HBeAg, ALT and HBV DNA levels were determined after a median of 9.2 years of follow-up of 124 adults with chronic HBV infection, of whom 33 were HBeAg-positive at inclusion.Results: HBV DNA levels decreased significantly in patients carrying genotype A (n = 28), B (n = 21) or D (n = 63), but not in those with genotype C infection (n = 12). Loss of HBeAg was seen in 44% (4/9) of patients with genotype C, as compared with 92% (22/24) with non-C genotypes. Loss of HBsAg was seen in 36% (10/28) patients with genotype A, 5% (1/21) with B, 0% (0/12) with C, and 11% (7/63) with genotype D.Conclusions: HBV DNA levels decreased over time in patients infected with genotypes A, B or D. However, highly active genotype C or D infection often remained highly active, implying a risk for progressive liver damage. (c) 2012 Elsevier B.V. All rights reserved.

BACKGROUND:Patients infected with hepatitis C virus (HCV) genotype 1 respond poorly to standard treatment with 50% or less achieving sustained virologic response. Predicting outcome is essential and could help avoid unnecessary treatment and reduce health cost. Recently, an association of amino acid substitutions in the core region and treatment outcome was observed in Japanese patients. In the present study, the impact of these mutations on response kinetics and treatment outcome was explored in Caucasian patients.METHODS:The core region of HCV pre-treatment samples obtained from 50 patients treated with peginterferon/ribavirin in a previous Swedish clinical trial with genotype 1 infection were sequenced. The alleles at rs12979860, a single nucleotide polymorphism (SNP), were assessed in order to identify any co-association with this strong response predictor.RESULTS:No association between treatment response and substitutions of core residue 91 was found. In contrast, substitutions of core residue 70 were observed in 6/21 (29%) non-responders, but only in one of 29 responders (p = 0.03), and were more common in subgenotype 1b (R70Q in 6 of 13 strains) than in 1a (R70P in 1 of 37 strains, p = 0.004). The rs12979860 SNP upstream of the IL28B gene was overall the strongest response predictor (p = 0.0001). Core 70 substitutions were associated with poorer response kinetics in patients carrying the CT genotype at rs12979860.CONCLUSIONS:The results indicate that substitutions of core residue 70 are related to treatment response in Caucasian patients with HCV-1b infection, but are of less importance than IL28B polymorphism.

ABSTRACT We monitored early viral response during the treatment of hepatitis C virus (HCV) infection with the aim of identifying predictors of treatment outcome. We studied 53 patients with genotype 1 infection who received 180 μg/week pegylated interferon alfa-2a and 1,000 or 1,200 mg/day ribavirin depending on body weight and serially assessed HCV RNA in serum, using the Cobas TaqMan assay. Thirty-one patients (58%) achieved sustained viral response (SVR). SVR was obtained in 100% (10/10) of patients with pretreatment viremia concentrations below 400,000 IU/ml, in 100% (14/14) of patients with more than 1.5 log reduction of HCV RNA after 4 days of treatment, and in 95% (22/23) of patients with a rate of decline in viremia higher than 0.70 log units/week during the second phase. Non-SVR was seen in all patients with a second-phase decline rate lower than 0.35 log units/week. Patients with slopes between 0.50 and 0.80 log units/week achieved SVR (4/4) unless the treatment dose was modified (3/3). We conclude that the second-phase slope appears to be an accurate and useful predictor of treatment response. On the basis of these findings, we propose a model of tailored treatment which takes into account the second-phase slope and the amount of HCV RNA after 21 days of treatment.

Long-path DOAS (differential optical absorption spectroscopy) in the ultraviolet spectral region has been shown to be applicable for low-concentration measurements of light aromatic hydrocarbons. However, because of spectral interferences among different aromatics as well as with oxygen, ozone, and sulfur dioxide, the application of the DOAS technique for this group of components is not without problems. This project includes a study of the differential absorption characteristics, between 250 and 280 nm, of twelve light aromatic hydrocarbons representing major constituents in technical solvents used in the automobile industry. Spectral overlapping between the different species, including oxygen, ozone, and sulfur dioxide, has been investigated and related to the chemical structure of the different aromatics. Interference effects in the DOAS application due to spectral overlapping have been investigated both in quantitative and in qualitative terms, with data from a field campaign at a major automobile manufacturing plant.