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Bepirovirsen is a developmental antisense oligonucleotide (ASO) for treatment of chronic hepatitis B virus infection. No pharmacokinetic (PK) studies comparing participants with hepatic impairment (HI) and healthy participants (HPs) have been conducted with ASOs. Given the target patient population, characterization of bepirovirsen PK in HI was imperative. This phase 1, nonrandomized, open‐label study (NCT04971928) evaluated the PKs of a single 300‐mg dose of bepirovirsen in participants with HI and matched HPs, enrolled in 2 parts (Part 1: moderate HI; Part 2: mild HI). If no predefined difference in the area under the concentration‐time curve from time 0 (predose) to infinite time (AUC0‐∞) and maximum observed concentration (Cmax; geometric mean ratio [GMR] 0.5‐1.5) was identified in Part 1, findings were applied to mild HI, eliminating Part 2. Participants were monitored for 50 days post‐treatment and noncompartmental analysis estimated PK parameters. Twenty‐four participants (moderate HI, n = 12; HP, n = 12) received bepirovirsen and completed Part 1. AUC0‐∞ and Cmax were lower in participants with moderate HI (GMR 0.69 and 0.67, respectively) than in HPs, while apparent clearance (CL/F) and apparent terminal phase volume of distribution (Vz/F) were higher (GMR 1.44 and 1.64, respectively), but fell within the predefined thresholds of difference for this study. Part 2 was omitted. Adverse events were mild. Moderate HI did not have a clinically relevant impact on bepirovirsen PK or safety. [ABSTRACT FROM AUTHOR]

Foreign‐born (FB) persons represent a large proportion of adults with chronic hepatitis B (CHB) in Canada due to higher prevalence rates in countries of birth for FB persons. Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of Canada HDV prevalence. We aim to provide an assessment of CHB and HDV prevalence in Canada using a comprehensive literature review and meta‐analysis. A comprehensive literature review of articles reporting HBsAg seroprevalence and anti‐HDV prevalence was conducted to calculate country‐specific rates and pooled prevalence of CHB and HDV using meta‐analyses. Country‐specific CHB and HDV rate estimates were combined with number of FB persons in Canada in 2021 from Statistics Canada to estimate total numbers of FB with CHB and HDV, respectively. These estimates were combined with estimates of Canada‐born persons with CHB and HDV to yield the total number of persons with CHB and HDV. In 2021, we estimated 0.550 million (M) (95% CI 0.488–0.615) persons with CHB; 0.344 M (95% CI 0.288–0.401) were FB and 0.206 M (95% CI: 0.200–0.214) were Canada‐born. The weighted average HDV prevalence among FB persons in Canada was 5.19% (17,848 [95% CI 9611–26,052] persons), among whom 50% emigrated from Asia and 31% from Africa. When combined with estimates of Canada‐born persons with HDV, we estimate 35,059 (95% CI: 18,744–52,083) persons with HDV in Canada. In conclusion, we estimate 0.550 M and 35,059 persons living with CHB and HDV, respectively, in Canada in 2021. [ABSTRACT FROM AUTHOR]

Timely antiviral therapy is critical in chronic hepatitis B cirrhosis to prevent further liver complications. Among a national cohort of US Veterans with chronic hepatitis B cirrhosis, only 52% were initiated on antiviral therapy; treatment was significantly lower among patients of non-Asian ethnicity, high-risk alcohol use, and in rural settings. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B is a major public health concern as one third of the world's population is infected with hepatitis B virus (HBV). The risk of HBV infection remains primarily through percutaneous or mucosal contact with infected blood or body fluids. Aim: To update the society on hepatitis B immunization strategies and its associated factors. Materials and Methods: The review paper utilized different search engines such as Pubmed Central, Scopus, Web of Science, Google Scholar, and so on to conduct this review paper. Results: Improving immunity through general vaccination recommendations has reduced the number of chronic hepatitis B cases among children and adolescents, but an influx of infections from endemic countries has increased the number of chronically infected adults. This is due to immigration from endemic countries to Hepatitis less burden areas like developed countries. Introduction of infant immunization programs in some countries has reportedly reduced the prevalence of HBV infection and reduced the incidence of liver cancer in children and young adults. Conclusion: While hepatitis B vaccination coverage is low, a significant number of people are not adhering to full hepatitis B vaccination posing a potential hazard to health. [ABSTRACT FROM AUTHOR]

Despite universal vaccination of newborns, the prevalence of chronic hepatitis virus B (HBV) infection and the associated disease burden remain high among adults in China. We investigated risk factors for chronic HBV infection in a community-based study of 512,726 individuals aged 30–79 years recruited from ten diverse areas during 2004–2008. Multivariable logistic regression was used to estimate odds ratios (ORs) of hepatitis B surface antigen (HBsAg) positivity recorded at baseline by sociodemographic and lifestyle factors, and medical history. In a random subset (n = 69,898) we further assessed the association of 18 single nucleotide polymorphisms (SNPs) previously shown to be associated with HBsAg positivity and development of chronic liver disease (CLD) (1600 cases). Several factors showed strong associations with HBsAg positivity, particularly younger age (< 40 vs. ≥ 60 years: OR 1.48, 95% CI 1.32–1.66), male sex (1.40, 1.34–1.46) and urban residency (1.55, 1.47–1.62). Of the 18 SNPs selected, 17 were associated with HBsAg positivity, and 14 with CLD, with SNPs near HLA-DPB1 were most strongly associated with both outcomes. In Chinese adults a range of genetic and non-genetic factors were associated with chronic HBV infection and CLD, which can inform targeted screening to help prevent disease progression. [ABSTRACT FROM AUTHOR]

Background An estimated 862 000 to 2.4 million people have chronic hepatitis B infection (CHB). Hepatitis B screening is recommended for pregnant women and populations with increased CHB risk. However, diagnosis rates remain low, with only 33% of people with CHB aware of their infection. This study aimed to assess the cost-effectiveness of universal adult screening for CHB. Methods We used a Markov model to calculate the costs, population health impact, and cost-effectiveness of 1-time universal screening and CHB monitoring and treatment compared with current practice. Sensitivity analysis was performed on model parameters to identify thresholds for cost-saving or cost-effectiveness based on a willingness to pay of $50 000/quality-adjusted life-year. The analysis assumed testing would be performed during routine healthcare visits and that generic tenofovir or entecavir would be dispensed for treatment. Testing costs were based on Medicare reimbursement rates. Results At an estimated 0.24% prevalence of undiagnosed CHB, universal hepatitis B surface antigen (HBsAg) screening in adults aged 18–69 years is cost-saving compared with current practice if antiviral treatment drug costs remain below $894/year. Compared with current practice, universal screening would avert an additional 7.4 cases of compensated cirrhosis, 3.3 cases of decompensated cirrhosis, 5.5 cases of hepatocellular carcinoma, 1.9 liver transplants, and 10.3 hepatitis B virus–related deaths at a saving of $263 000/100 000 adults screened. Conclusions Universal HBsAg screening of adults in the US general population for CHB is cost-effective and likely cost-saving compared with current CHB screening recommendations. [ABSTRACT FROM AUTHOR]

Introduction Liver cirrhosis is an important cause of morbidity and mortality. Methods Our study aimed to describe the aetiologies of liver cirrhosis and its associated risk factors among adult patients attending the Hepatology Clinic, Serdang Hospital, Malaysia from 1st January 2010 to 30th June 2017. Aetiology was determined by patients' medical history as well as biochemical and/or histological findings. The severity of the liver cirrhosis, together with the presence of complications and incidence of hepatocellular carcinoma were documented. Results A total of 357 adult patients were diagnosed with liver cirrhosis including 199 male patients (55.7%) and 158 female patients (44.3%), with a mean age of 54-year-old (range: 28--84 --year-old). The determined most likely causes of liver cirrhosis were chronic hepatitis B (N=145, 40.6%), chronic hepatitis C (N= 67, 18.8%), cryptogenic liver disorder (N= 63, 17.6%), alcohol (N=42, 11.8%), non-alcoholic fatty liver disease (N=25, 7.0%), and others (N=15, 4.2%). Chronic hepatitis B was predominant among Chinese whereas alcohol consumption was mainly found among Indians, and Hepatitis C-linked liver cirrhosis was highest among Malays. Majority of the patients had compensated cirrhosis with Child-Pugh A (N=221, 61.9%) at the time of diagnosis. 80.4% (N=287) of the cirrhotic patients had performed at least one endoscopy surveillance, with 28.6% (82/287) of them had endoscopic evidence of portal hypertension. 32.2% of patients had at least one hospitalization due to complication of cirrhosis. 41 patients (11.5%) had concurrent hepatocellular carcinoma during the follow up. Conclusions Hepatitis B viral infection remains the most common cause of cirrhosis among patients attending Hepatology Clinic, Serdang Hospital. [ABSTRACT FROM AUTHOR]

Background: In 2019, an estimated 296 million people were living with chronic hepatitis B virus (HBV) globally with approximately 2.4 million living within the United States. Those living with HBV require years if not decades of regular monitoring to prevent liver complications from occurring. The aim of this study was to explore the working conceptual framework of health related quality of life (HRQL) for those living with chronic HBV through qualitative analysis. Methods: Data were collected by in-depth telephone interviews conducted in 2019 using purposeful sampling as part of a disease understanding assessment on the HBV patient experience within the United States. A directed content analysis approach was utilized by creation of a codebook to guide the organization of data, codes were developed by review of the literature (a priori) and through line-by-line reading of a subsample of queries. All transcripts were analyzed by at least two members of the study team and intercoder reliability was assessed using Dedoose software. Findings: A sample of 19 individuals living with chronic HBV were included within this study. Themes identified from transcripts noted the significant overlap between the reported experience of HBV and constructs within the HRQL model. The psychological impact of chronic HBV on study participants' HRQL overall was considerable and contributed to depression, anxiety, homelessness, drug use, and incarceration. Conclusion: Our analysis supports the hypothesis that HBV impacts HRQL and often negatively affects emotional health. Our findings suggest that it would be beneficial to include HRQL assessment in the medical management of HBV, so that interventions can focus on reducing the burden of disease and improving quality of life for those living with HBV. [ABSTRACT FROM AUTHOR]

Summary: Background: As the prevalence of hepatitis steatosis (HS) increases, the prevalence of HS among those with chronic hepatitis B (CHB) may also be increasing but data on the effect of HS on CHB disease progression are lacking. Aims: To determine the prevalence of HS in CHB and associated factors, prevalence of fibrosis and its association with HS. Methods: Two researchers independently searched the literature and extracted data. We included full‐length original articles of adults with CHB that evaluated. Prevalence estimates were pooled using a random‐effects model. Associations between HS and fibrosis were assessed by pooled odds ratios (ORs) or mean differences (MD). Results: Of the 2821 records screened, 54 eligible studies (28 648 patients) were analysed. The pooled prevalence of HS in CHB was 32.8% (95% CI, 28.9‐37.0) with higher prevalence in men and obese patients. Older age, male sex and metabolic factors were associated with HS while an inverse association was observed between HS and HBeAg (OR 0.82, 95% CI, 0.75‐0.91) and HBV DNA levels (MD −0.38, 95% CI −1.16‐−0.42). The pooled prevalence of significant fibrosis (≥F2 or ≥F3) was similar between patients with CHB with or without HS (40.1% vs 42.22%, P = 0.68). HS was not significantly associated with fibrosis (pooled OR 0.87, 95% CI 0.54‐1.39, 20 studies, 6232 patients). Conclusions: Approximately 30% of patients with CHB had HS, which was positively associated with male sex, diabetes and metabolic factors, and was negatively associated with HBeAg and HBV DNA. HS was not significantly associated with increased fibrosis. [ABSTRACT FROM AUTHOR]

While hepatitis E virus (HEV) infection can increase the risk of liver decompensation and death in patients with underlying chronic liver disease (CLD), prevalence of HEV in this cohort is not well reported. Using data from the 2011–2018 National Health and Nutrition Examination Survey, we aim to evaluate seroprevalence of HEV IgG among adults with non‐alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), chronic hepatitis C virus (HCV) and chronic hepatitis B virus (HBV). HEV IgG seroprevalence between groups was evaluated with chi‐square testing, and adjusted multivariate logistic regression models evaluated for predictors of seropositivity for HEV IgG. Seroprevalence of HEV IgG was 6.58% in ALD, 8.66% in HCV, 8.81% in NAFLD and 19.86% in HBV. We observed increasing HEV IgG seroprevalence over time in our study period, and in 2015–2018, seroprevalence was highest among the individuals with HCV (10.00%) and HBV (30.30%). Older age and being born outside of the United States were associated with seropositivity for HEV IgG in ALD, NAFLD, HBV, and for HCV, older age and being at or below poverty level were associated with seroprevalence for HEV IgG. In conclusion, we observed a relatively high prevalence of HEV among adults with CLD. These data highlight the need for greater awareness and education about the role of HEV in patients with underlying CLD, improving HEV test diagnostics, and revisiting the discussion about the potential role of HEV vaccines in CLD patients who are at higher risk of decompensation and death from acute HEV infection. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B prevalence is low in most Australian populations, with universal infant HBV vaccination introduced in 2000. Migrants from high prevalence countries are at risk of acquisition before arrival and non‐immune adults are potentially at risk through skin penetrating procedures and sexual contact, particularly during international travel. The risk profile of young adult students, many from high prevalence countries, is inadequately understood. A cross‐sectional online survey conducted among university students collected data on demographic, vaccination and travel characteristics and blood samples were tested for hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb). Analyses identified factors associated with HBsAb seroprevalence and self‐reported vaccination. The serosurvey was completed by 804 students born between 1988 and 1993, with 613/804 (76.2%, 95% CI 73.2–79.1) self‐reporting prior HBV vaccination. Overall, 526/804 (65.4%, 95% CI 62.0%–68.6%) students were seropositive to HBsAb, including 438/613 (71.5%, 95% CI 67.8–74.9) students self‐reporting a prior HBV vaccine and 88/191 (46.1%, 95% CI 39.2–53.2) students self‐reporting no prior HBV vaccine. Overall, 8/804 (1.0%, 95% CI 0.5%–2.0%) students were HBcAb positive, of whom 1/804 (0.1%, 95% CI 0.02%–0.7%) was currently infectious. The prevalence of chronic HBV infection was low. However, more than one in four students were susceptible to HBV and over‐estimated their immunity. Future vaccination efforts should focus on domestic students born before the introduction of the infant program and all international students. Screening and vaccination of students, including through campus‐based health services, are an opportunity to catch‐up young adults prior to undertaking at‐risk activities, including international travel. [ABSTRACT FROM AUTHOR]

Background & Aims: Several studies suggested that efficacy of tenofovir in reducing the risk of the development of hepatocellular carcinoma (HCC) might be better than that of entecavir. It remains unknown whether a change in therapy can further reduce the risk of HCC in patients receiving entecavir therapy and achieved goal of antiviral therapy, a maintained undetectable hepatitis B virus (HBV) DNA level in the serum. Methods: A total of 1336 treatment‐naïve chronic HBV mono‐infected adult patients, who started entecavir or tenofovir treatment and achieved a maintained virologic response during follow‐up were analysed. Results: During a median 4.4 years of follow‐up (range, 1.0–7.4 years) after achieving virologic response, 99 patients developed HCC. The 5‐year cumulative HCC incidence rate was 7.3% and 6.3% for the entecavir and tenofovir groups, respectively, with similar risk of HCC between the two groups (adjusted HR, 0.82; 95% CI, 0.52–1.29; p = 0.3). The risk of HCC was similar in the propensity score‐matched cohort (HR, 1.02; 95% CI, 0.68–1.52; p = 0.94) and inverse probability treatment weighting analysis (HR, 1.11; 95% CI, 0.74–1.66; p = 0.62). In the subgroup analysis, HCC risk was similar between the two drugs in both patients with and without cirrhosis. Discussion: In patients showing maintained virologic response, no difference in the risk of HCC between entecavir and tenofovir was observed. This indicates entecavir might be as effective as tenofovir in the prevention of HCC among those patients and suggest that a change in therapy in anticipation of further reducing the risk of HCC might not be necessary for patients receiving entecavir and showing virologic response. [ABSTRACT FROM AUTHOR]

• HEPLISAV-B is a 2-dose Hepatitis B virus vaccine recently available in the US. • HEPLISAV-B offers earlier and higher levels of seroprotection than 3-dose Engerix-B. • HEPLISAV-B was cost-effective vs Engerix-B for multiple high-risk adult populations. • HEPLISAV-B was cost-effective for universal vaccination of adults. The hepatitis B virus is highly infectious and can cause incurable liver disease, leading to high morbidity rates, increased healthcare utilization, and high mortality. Multiple preventative hepatitis B vaccine options have been available for decades, but adherence to the traditional 6-month vaccine schedule for the approved 3-dose series remains low in adult populations at risk of hepatitis B exposure. A 2-dose hepatitis B vaccine (HEPLISAV-B) approved by the US Food and Drug Administration in 2017 induces rapid seroprotection within 1 month and has a safety profile comparable to a commonly used 3-dose vaccine. In a previous cost-effectiveness study, HEPLISAV-B had a favorable cost-effectiveness profile for multiple at-risk populations. The goal of the current analysis was to update and extend previous findings by evaluating cost-effectiveness of HEPLISAV-B compared with a 3-dose vaccine (Engerix-B) in selected adult populations, including patients with diabetes, chronic liver or kidney disease, end-stage renal disease, healthcare personnel, travelers to countries with endemic hepatitis B, and a public health population. Cost-effectiveness was measured as incremental cost-effectiveness ratios using a health economics Markov model that accounts for adherence rates, seroprotection rates, healthcare costs, and current pricing considerations. Patients progressed between a series of health states, and the difference in lifetime spending and survival for individuals receiving either HEPLISAV-B or Engerix-B was estimated from the perspective of a US managed care payer, HEPLISAV-B had favorable cost-effectiveness profiles for patients with diabetes, healthcare personnel, travelers, and patients with chronic liver disease and dominant incremental cost-effectiveness ratios for patients with chronic kidney disease and end-stage renal disease. A probabilistic sensitivity analysis supported the robustness of the cost-effectiveness profiles, and an additional analysis indicated that HEPLISAV-B was cost-effective in the general adult population. Overall, HEPLISAV-B was cost-effective in multiple adult populations recommended for HBV vaccination in the United States. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Bulevirtide (BLV, Hepcludex®) is an HDV/HBV entry inhibitor approved in June 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease and positive HDV RNA viral load. This real‐life preliminary report described early virological efficacy and safety of BLV in six patients with CHD and compensated liver disease: four patients were treated with the combination of BLV (2 mg/d in subcutaneous injection) and pegylated interferon (PEG‐IFN) and two patients with BLV monotherapy. Four patients treated with combined therapy had a decline of a minimum of 1 log10 and 3/3 of 2 log10 of HDV‐VL at 12 and 24 weeks, respectively. One patient among four had stopped the treatment at 12 weeks because of thrombocytopenia and an HDV‐VL relapse was notified 24 weeks after treatment cessation. Three patients among four (3/4) had undetectable HDV‐VL during the therapy (<100 IU/ml). One patient (1/2) treated with BLV monotherapy had a decline of HDV‐VL by 1 log10 at 8 weeks and 1/1 by 2 log10 at 28 week on‐treatment. Two patients among four (2/4) with combined therapy had normal ALT reached at 4 and 56 weeks. One patient (1/2) with BLV monotherapy achieves ALT normalization at​ 4 weeks on treatment. Hepatitis B surface antigen (HBsAg) levels remain unchanged. Three among six (3/6) patients had an elevation of total biliary acids without pruritus. These early data generated confirm the interest in this new treatment. Final results will be important to demonstrate long‐term clinical benefit (fibrosis reversibility and reduction in hepato‐cellular carcinoma [HCC]). [ABSTRACT FROM AUTHOR]

To investigate the characteristics of the immunoglobulin light-chain repertoires with chronic HBV infection, the high-throughput sequencing and IMGT/HighV-QUEST were adapted to analyze the κ (IgK) and λ (IgL) light-chain repertoires from the inactive HBV carriers (IHB) and the healthy adults (HH). The comparative analysis revealed high similarity between the κ light-chain repertoires of the HBV carriers and the healthy adults. Nevertheless, the proportion of IGLV genes with ≥90% identity as the germline genes was higher in the IgL light-chain repertoire of the IHB library compared with that of HH library (74.6% vs. 69.1%). Besides, the frequency of amino acid mutations in the CDR1 regions was significantly lower in the IgL light-chain repertoire of the IHB library than that of the HH library (65.52% vs. 56.0%). These results suggested the lower somatic mutation level in the IgL repertoire of IHB library, which might indicate the biased selection of IGLV genes in the IgL repertoire with chronic HBV infection. These findings might lead to a better understanding of the characteristics of the light-chain repertoires of HBV chronically infected individuals. [ABSTRACT FROM AUTHOR]

• The response rate and high-level response rate of the IM60 group were numerically higher than those of the IM20 group at different follow-up points. • The duration of the vaccine-induced responses with 25% of patients with anti-HBs ≥ 10 mIU/mL were 20 months in the IM60 group, and 9.3 months in the IM20 group. • Patients with CD4 ≥ 350 per µL induced higher response rate than the patients with CD4 < 350 per µL at month 7. • No Serious Adverse Events (SAEs) related to vaccination was reported at each follow-up points. To explore the immunogenicity and persistence of the 60 µg hepatitis B vaccine in adults infected with human immunodeficiency virus (HIV). We conducted a randomised controlled trial for adults infected with HIV. A total of 182 patients were randomly allocated to receive 20 µg (IM20 group) or 60 µg (IM60 group) of recombinant hepatitis B vaccine at months 0, 1, and 6 to assess the immunogenicity and were followed-up from month 7 to 42 to assess long-term immunogenicity. Our data showed that the response rate and geometric mean concentration (GMC) of antibodies to hepatitis B surface antigen (anti-HBs) in the IM60 group at month 7 were higher than those in the IM20 group (P > 0.05). The GMC of anti-HBs among the two groups decreased rapidly during the follow-up period (P > 0.05). Survival analysis showed that 25% of patients with anti-HBs ≥ 10 mIU/mL were 20 months in the IM60 group and 9.3 months in the IM20 group. The three-dose 60 µg hepatitis B vaccine showed partially better immunogenicity and persistence than the three-dose 20 µg vaccine. The trial was registered on clinicaltrials.gov, NCT03316807. [ABSTRACT FROM AUTHOR]

• Phase 1 study of HEPLISAV-B in hemodialysis patients. • Four doses of HEPLISAV-B induced high level of seroprotection and were well tolerated. Hemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and are poorly responsive to HBV vaccines. Current vaccine recommendations for hemodialysis patients utilize more than twice the amount of hepatitis B surface antigen (HBsAg) used for healthy adults and achieve lower immune responses. An open-label, single-arm, multicenter trial was conducted among adults 18 years of age and older who were initiating or undergoing hemodialysis who had not previously received hepatitis B vaccine. Participants received four doses of HepB-CpG (HEPLISAV-B®) (20 mcg rHBsAg + 3000 mcg CpG 1018, a Toll-like receptor 9 agonist) administered at 0, 4, 8, and 16 weeks. Participants are being followed for 68 weeks. This paper reports the final immunogenicity analysis of the primary endpoint at study week 20 and an interim safety analysis. We enrolled 119 participants receiving hemodialysis who were followed for a median of 47.4 weeks. Of the 119 participants, 75 were in the per-protocol population. At week 20, the seroprotection rate (% with antibodies to hepatitis B surface antigen [anti-HBs] ≥ 10 mIU/mL) was 89.3% and the percentage of participants with anti-HBs ≥ 100 mIU/mL was 81.3%. The anti-HBs geometric mean concentration was 1061.8 mIU/mL. HepB-CpG was well tolerated with no observed safety concerns. In patients receiving hemodialysis, HepB-CpG given as four doses was well tolerated and induced very high anti-HBs concentrations and seroprotection in a very high proportion of recipients. [ABSTRACT FROM AUTHOR]

Background: In patients co-infected with HIV and tuberculosis, antiretroviral therapy options are limited due to drug-drug interactions with rifampicin. A previous phase 2 trial indicated that raltegravir 400 mg twice a day or efavirenz 600 mg once a day might have similar virological efficacy in patients given rifampicin. In this phase 3 trial, we assessed the non-inferiority of raltegravir to efavirenz.Methods: We did a multicentre, open-label, non-inferiority, randomised, phase 3 trial at six sites in Côte d'Ivoire, Brazil, France, Mozambique, and Vietnam. We included antiretroviral therapy (ART)-naive adults (aged ≥18 years) with confirmed HIV-1 infection and bacteriologically confirmed or clinically diagnosed tuberculosis who had initiated rifampicin-containing tuberculosis treatment within the past 8 weeks. Using computerised random numbers, we randomly assigned participants (1:1; stratified by country) to receive raltegravir 400 mg twice daily or efavirenz 600 mg once daily, both in combination with tenofovir and lamivudine. The primary outcome was the proportion of patients with virological suppression at week 48 (defined as plasma HIV RNA concentration <50 copies per mL). The prespecified non-inferiority margin was 12%. The primary outcome was assessed in the intention-to-treat population, which included all randomly assigned patients (excluding two patients with HIV-2 infection and one patient with HIV-1 RNA concentration of <50 copies per mL at inclusion), and the on-treatment population, which included all patients in the intention-to-treat population who initiated treatment and were continuing allocated treatment at week 48, and patients who had discontinued allocated treatment due to death or virological failure. Safety was assessed in all patients who received at least one dose of the assigned treatment regimen. This study is registered with ClinicalTrials.gov, NCT02273765.Findings: Between Sept 28, 2015, and Jan 5, 2018, 460 participants were randomly assigned to raltegravir (n=230) or efavirenz (n=230), of whom 457 patients (230 patients in the raltegravir group; 227 patients in the efavirenz group) were included in the intention-to-treat analysis and 410 (206 patients in the raltegravir group; 204 patients in the efavirenz group) in the on-treatment analysis. At baseline, the median CD4 count was 103 cells per μL and median plasma HIV RNA concentration was 5·5 log10 copies per mL (IQR 5·0-5·8). 310 (68%) of 457 participants had bacteriologically-confirmed tuberculosis. In the intention-to-treat population, at week 48, 140 (61%) of 230 participants in the raltegravir group and 150 (66%) of 227 patients in the efavirenz had achieved virological suppression (between-group difference -5·2% [95% CI -14·0 to 3·6]), thus raltegravir did not meet the predefined criterion for non-inferiority. The most frequent adverse events were HIV-associated non-AIDS illnesses (eight [3%] of 229 patients in the raltegravir group; 21 [9%] of 230 patients in the efavirenz group) and AIDS-defining illnesses (ten [4%] patients in the raltegravir group; 13 [6%] patients in the efavirenz group). 58 (25%) of 229 patients in raltegravir group and 66 (29%) of 230 patients in the efavirenz group had grade 3 or 4 adverse events. 26 (6%) of 457 patients died during follow-up: 14 in the efavirenz group and 12 in the raltegravir group.Interpretation: In patients with HIV given tuberculosis treatment, non-inferiority of raltegravir compared with efavirenz was not shown. Raltegravir was well tolerated and could be considered as an option, but only in selected patients.Funding: National French Agency for AIDS Research, Ministry of Health in Brazil, Merck.Translations: For the Portuguese and French translations of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: Data from the USA suggest that chronic hepatitis B (CHB) patients have aged in the past decade. However, the burden of nonliver comorbidities has not been well characterized in Taiwan, where CHB is very prevalent. Aim: Our study examined this issue as it presented between 2001 and 2011 in Taiwan. Methods: This study identified adult patients (≥18 years) who were diagnosed with CHB in 2001, 2006, and 2011, from the Taiwan National Health Insurance Research Database (NHIRD). Changes in demographic characteristics, prevalence of nonliver comorbidities, and medication usage over the decade were examined. Non-CHB controls were adults without CHB diagnosis from the Longitudinal Health Insurance Database 2000 (LHID2000). Results: A total of 102,158, 252,809, and 338,200 eligible patients were identified in 2001, 2006, and 2011, respectively. The mean age significantly advanced from 45.4 to 52.3 years over the decade (p < 0.001). The prevalence of comorbidities, including diabetes mellitus, hypertension, stroke, chronic kidney disease, and bone fracture, significantly increased between 2001 and 2011 (all p < 0.001), as so were medication usage (all p < 0.001). Moreover, within each study period, compared to non-CHB controls, CHB patients were also older and more likely to have metabolic and cardiovascular comorbidities (all p < 0.001). In addition, the annual nonliver mortality in the CHB population significantly increased from 2001 to 2011. Conclusions: Over a decade, the CHB population in Taiwan has aged with a higher nonliver comorbidity burden and increasing nonliver mortality. These findings may provide information to care providers in the monitoring and management of CHB patients. [ABSTRACT FROM AUTHOR]

The USPSTF has made recommendations on screening for HBV infection in pregnant persons, hepatitis C virus infection in adolescents and adults, and HIV infection. April 15, 2021 Volume 103, Number 8 www.aafp.org/afp American Family Physician 495 U.S. Preventive Services Task Force Screening for Hepatitis B Virus Infection in Adolescents and Adults: Recommendation Statement Summary of Recommendation The USPSTF recommends screening for hepatitis B virus (HBV) infection in adolescents and adults at increased risk for infection (Table 1). These include screening for HBV infection during pregnancy 8; screening for hepatitis C virus infection in adults aged 18 to 79 years 27; screening for HIV in adolescents and adults aged 15 to 65 years 28; and behavioral counseling to prevent sexually transmitted infections. [Extracted from the article]

What is known and objective: The frequent tenofovir disoproxil fumarate (TDF)‐related adverse drug reactions (ADRs) are nephrotoxicity and bone toxicity; however, tooth‐related ADRs of TDF have not been reported. We describe the case of a 41‐year‐old Han Chinese man with chronic hepatitis B with TDF‐associated tooth loss. Case summary: He presented with halitosis, gingival swelling and tooth loss after TDF use. After excluding the possibility of other drug‐related ADRs, TDF was considered a possible cause and switched with tenofovir alafenamide fumarate (TAF). After 6 months, the oral symptoms disappeared, with no additional tooth loss. What is new and conclusion: This is the first report of such ADRs. The ADR score was 7, indicating tooth loss as a potential TDF‐related ADR. [ABSTRACT FROM AUTHOR]

Objective: The study was conducted to estimate the prevalence of chronic hepatitis B infection and related factors among adult population in Central Highland, 2018. Methods: The study applied the cross-sectional descriptive design with the combination of structured interview and serological blood tests. There were 2428 respondents in 03 provinces, namely Kon Tum, Gia Lai, Dak Nong included in the study which was conducted from September to December 2018. Results: The prevalence of hepatitis B infection among adults in Central Highland was 11.2% with the positive uniformity among provinces in the region. The findings also showed that male adults, farmers and those who have relatives with liver disease and experienced the kidney dialysis possessed a higher rate of hepatitis B virus infection than the one of other groups. The findings also showed that the respondents had a low uptake of the vaccine among infected group (6.3%). Study subjects with vaccination were less affected by hepatitis B virus infection rate than the ones without vaccination. Conclusions: The high prevalence of chronic hepatitis B in the Central Highland indicates that it needs much more attention of Ministry of Health and local authorities for prevention of infection through mother-to-child transmission and early infection due to late immunization and more rescue investment for diagnostic, evaluation, follow up and treatment of people with chronic HBV infection. The consideration regarding occupations, family history of liver diseases is also required for during the intervention implementation. [ABSTRACT FROM AUTHOR]

Background. Traditional Chinese medicine (TCM) is used as an adjuvant drug for the treatment of chronic hepatitis B liver fibrosis and is used frequently. We still do not know which TCM has the best curative effect as an adjuvant drug. Therefore, we decided to use network meta-analysis to solve this problem. Methods. We used the RevMan software (5.3) and Stata software (13.0) to achieve this network meta-analysis (NMA). The primary outcomes of this study were HA, LN, PCIII, and IV-C; the secondary outcomes of this study were AST, ALT, and HBV-DNA negative conversion rate, and the Cochrane risk-of-bias tool was used to assess the quality of the included studies. For all outcomes, the scissors funnel plot, Egger test, and Begg test were used to detect publication bias, and sensitivity analysis was used to investigate the stability of the results. And the meta-regression was used to explore the source of heterogeneity. Results. A total of 34 articles were included in this study. The study involved a total of 3199 patients, of which 1578 were assigned to the control group and 1621 patients were assigned to the experimental group. The number of men and women is roughly equal, and the average age is about 43 years old. In addition, nine treatment strategies were involved in this study. The combination of TCM and entecavir can significantly improve the patients' HA, LN, PCIII, IV-C, AST, ALT, and HBV-DNA negative conversion rates. The comprehensive evaluation results showed that FHC combined with entecavir has more advantages than other treatment strategies. Conclusion. For improving the HBV-DNA negative conversion rates, adding TCM to the therapeutic strategies does not seem to show absolute superiority. Finally, FHC combined with entecavir is the best therapeutic strategy. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated antiviral therapy (AVT) eligibility in a population-based sample of adults with chronic hepatitis B virus (HBV) infection in Zambia. Materials and methods: Using a household survey, adults (18+ years) were tested for hepatitis B surface antigen (HBsAg). Sociodemographic correlates of HBsAg-positivity were identified with multivariable regression. HBsAg-positive individuals were referred to a central hospital for physical examination, elastography, and phlebotomy for HBV DNA, hepatitis B e antigen, serum transaminases, platelet count, and HIV-1/2 antibody. We determined the proportion of HBV monoinfected adults eligible for antiviral therapy (AVT) based on European Association for the Study of the Liver (EASL) 2017 guidelines. We also evaluated the performance of two alternative criteria developed for use in sub-Saharan Africa, the World Health Organization (WHO) and Treat-B guidelines. Results: Across 12 urban and 4 rural communities, 4,961 adults (62.9% female) were tested and 182 (3.7%) were HBsAg-positive, 80% of whom attended hospital follow-up. HBsAg-positivity was higher among men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 0.99–1.87) and with decreasing income (AOR, 0.89 per household asset; 95% CI, 0.81–0.98). Trends toward higher HBsAg-positivity were also seen at ages 30–39 years (AOR, 2.11; 95% CI, 0.96–4.63) and among pregnant women (AOR, 1.74; 95% CI, 0.93–3.25). Among HBV monoinfected individuals (i.e., HIV-negative) evaluated for AVT, median age was 31 years, 24.6% were HBeAg-positive, and 27.9% had HBV DNA >2,000 IU/ml. AVT-eligibility was 17.0% by EASL, 10.2% by WHO, and 31.1% by Treat-B. Men had increased odds of eligibility. WHO (area under the receiver operating curve [AUROC], 0.68) and Treat-B criteria (AUROC, 0.76) had modest accuracy. Fourteen percent of HBsAg-positive individuals were HIV coinfection, and most coinfected individuals were taking tenofovir-containing antiretroviral therapy (ART). Conclusion: Approximately 1 in 6 HBV monoinfected adults in the general population in Zambia may be AVT-eligible. Men should be a major focus of hepatitis B diagnosis and treatment. Further development and evaluation of HBV treatment criteria for resource-limited settings is needed. In settings with overlapping HIV and HBV epidemics, scale-up of ART has contributed towards hepatitis B elimination. [ABSTRACT FROM AUTHOR]

Purpose: To determine the frequency and socio‐demographic/clinical correlates of insomnia in patients with chronic hepatitis B, hepatitis B virus (HBV)‐related liver failure, and cirrhosis. Design and Methods: Up to 120 patients with HBV‐related diseases and 40 matched healthy controls were recruited. Depressive and anxiety symptoms, early, middle, and late insomnia were measured. Findings: The frequency of ≥1 type of insomnia was 64.2% in patients and 35.0% in controls; frequencies of early, middle, and late insomnia in patients were 39.2%, 42.5%, and 48.3%, respectively, compared to 22.5%, 10.0%, and 25.0% in controls. Urban residency was independently associated with less insomnia of any type, accounting for 22.6% of the variance. Practice Implications: A considerable proportion of patients with HBV‐related diseases suffer from insomnia that warrants more attention in clinical practice. [ABSTRACT FROM AUTHOR]

• CXCL10 SNP rs4508917 was associated with risk of chronic HBV infection in children. • R s4508917 A allele increased the transcriptional activity of CXCL10 in vitro. • Rs4508917 A allele had a limited HBV DNA suppression in patients treated with NAs. Chemokine (C-X-C motif) ligand 10 (CXCL10) has been recently shown to be associated with inflammatory diseases. However, the association between the genetic variation of this gene and the susceptibility to hepatitis B virus (HBV) infection remains unclear, especially in children. This study aimed to investigate the relationship between CXCL10 polymorphisms and the risk of chronic HBV infection in a Chinese Han population. A two-stage case-control study of 1048 adults and 627 children was performed. A total of 5 tagging SNPs in CXCL10 were genotyped. Dual-Luciferase Reporter Assay was used to assess the effect of the rs4508917 polymorphism on transcriptional activity of CXCL10. CXCL10 rs4508917 and rs4256246 polymorphisms were significantly associated with an increased risk of chronic HBV infection in Chinese Han adults (p = 0.036 and p = 0.033), of which rs4508917 AA genotype could increase the serum CXCL10 level (p = 0.014). In addition, the rs4508917 AA genotype was identified to facilitate HBV persistent infection (p = 0.017) and breakthrough infection (p = 0.013) in children. Subsequent functional analysis indicated that rs4508917 A allele could promote the transcriptional activity of CXCL10. Additionally, we observed that the rs4508917 A allele carriers (AA and AG genotypes) had a limited HBV viral load suppression in patients treated with nucleos(t)ide analogues (NAs). The A allele of the CXCL10 rs4508917 may be a risk factor of the persistent HBV infection both in adults and children, which may influence the response to NAs treatment. [ABSTRACT FROM AUTHOR]

(1) Background: The World Health Organization adopted a strategy for the Global Health Sector on Viral Hepatitis in 2016, with the main objective of eliminating hepatitis C virus (HCV) by 2030. In this work, we aimed to evaluate the prevalence of HCV infection and risk factors in a Romanian village using population-based screening as part of the global C virus eradication program. (2) Methods: We conducted a prospective study from March 2019 to February 2020, based on a strategy as part of a project designed to educate, screen, treat and eliminate HCV infection in all adults in a village located in Northeastern Romania. (3) Results: In total, 3507 subjects were invited to be screened by rapid diagnostic orientation tests (RDOT). Overall, 2945 (84%) subjects were tested, out of whom 78 (2.64%) were found to have positive HCV antibodies and were scheduled for further evaluation in a tertiary center of gastroenterology/hepatology in order to be linked to care. In total, 66 (85%) subjects presented for evaluation and 55 (83%) had detectable HCV RNA. Of these, 54 (98%) completed antiviral treatment and 53 (99%) obtained a sustained virological response. (4) Conclusions: The elimination of hepatitis C worldwide has a higher chance of success if micro-elimination strategies based on mass screening are adopted. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B is a serious and chronic health problem, requiring self-management to control the disease and related complications. To develop a structural model to identify how social support, self-efficacy and disease knowledge contribute to their self-management behaviors in adults with chronic hepatitis B. A cross-sectional study. Hepatology units in two hospitals in Chongqing, China. A total of 306 patients with chronic hepatitis B were recruited. Data were collected using Social Support Rating Scale, Self-Efficacy for Managing Chronic Disease, Hepatitis B Knowledge Questionnaire and Chronic Hepatitis B Self-Management Scale. Structural equation model was applied to analyze the data. The final model showed good model fit. Social support directly influenced self-management behaviors (β = 0.19, p < 0.01), and indirectly influenced self-management behaviors (β = 0.20, p < 0.01) through self-efficacy. Self-efficacy directly influenced self-management behaviors (β = 0.37, p < 0.05). Disease knowledge indirectly influenced self-management behaviors (β = 0.12, p < 0.05) through self-efficacy. Our findings indicated that social support, self-efficacy and disease knowledge directly or indirectly affected self-management behaviors in adults with chronic hepatitis B. This provides a theoretical basis for developing self-management interventions for patients with chronic hepatitis B, which may lead to health improvements in this population. [ABSTRACT FROM AUTHOR]