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Background Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are common among individuals with human immune deficiency virus (HIV) infection worldwide. In this study, we did a systematic review and meta-analysis of the published literature to estimate the global and regional prevalence of HCV, HBV and HIV coinfections among HIV-positive prisoners. Methods We searched PubMed via MEDLINE, Embase, the Cochrane Library, SCOPUS, and Web of science (ISI) to identify studies that reported the prevalence of HBV and HCV among prisoners living with HIV. We used an eight-item checklist for critically appraisal studies of prevalence/incidence of a health problem to assess the quality of publications in the included 48 cross-sectional and 4 cohort studies. We used random-effect models and meta-regression for the meta-analysis of the results of the included studies. Results The number of the included studies were 50 for HCV-HIV, and 23 for HBV-HIV co-infections. The pooled prevalence rates of the coinfections were 12% [95% confidence interval (CI) 9.0–16.0] for HBV-HIV and 62% (95% CI 53.0–71.0) for HCV-HIV. Among HIV-positive prisoners who reported drug injection, the prevalence of HBV increased to 15% (95% CI 5.0–23.0), and the HCV prevalence increased to 78% (95% CI 51.0–100). The prevalence of HBV-HIV coinfection among prisoners ranged from 3% in the East Mediterranean region to 27% in the American region. Also, the prevalence of HCV-HIV coinfections among prisoners ranged from 6% in Europe to 98% in the East Mediterranean regions. Conclusions Our findings suggested that the high prevalence of HBV and HCV co-infection among HIV-positive prisoners, particularly among those with a history of drug injection, varies significantly across the globe. The results of Meta-regression analysis showed a sliding increase in the prevalence of the studied co-infections among prisoners over the past decades, rising a call for better screening and treatment programs targeting this high-risk population. To prevent the above coinfections among prisoners, aimed public health services (e.g. harm reduction via access to clean needles), human rights, equity, and ethics are to be seriously delivered or practiced in prisons. Protocol registration number: CRD42018115707 (in the PROSPERO international). Graphic abstract

Chronic hepatitis and hepatocellular carcinoma (HCC) caused by the hepadnavirus hepatitis B virus (HBV) are significant causes of human mortality. A hepatitis-B-like virus infecting cats, domestic cat hepadnavirus (DCH), was reported in 2018. DCH DNA is hepatotropic and detectable in feline blood or serum (3.2 to 12.3%). Detection of HBV DNA has been reported in sera from 10% of free-roaming dogs in Brazil, whereas 6.3% of sera from dogs in Italy tested positive for DCH DNA by real-time quantitative PCR (qPCR). If DCH, HBV, or another hepadnavirus is hepatotropic in dogs, a role for such a virus in the etiology of canine idiopathic chronic hepatitis (CH) or HCC warrants investigation. This study investigated whether DCH DNA could be detected via qPCR in blood from dogs in Hong Kong and also whether liver biopsies from dogs with confirmed idiopathic CH or HCC contained hepadnaviral DNA using two panhepadnavirus conventional PCRs (cPCR) and a DCH-specific cPCR. DCH DNA was amplified from 2 of 501 (0.4%) canine whole-blood DNA samples. A second sample taken 6 or 7 months later from each dog tested negative in DCH qPCR. DNA extracted from 101 liver biopsies from dogs in Hong Kong or the USA, diagnosed by board-certified pathologists as idiopathic CH (n = 47) or HCC (n = 54), tested negative for DCH DNA and also tested negative using panhepadnavirus cPCRs. This study confirms that DCH DNA can be detected in canine blood by qPCR, although at a much lower prevalence than that reported previously. We identified no evidence to support a pathogenic role for a hepadnavirus in canine idiopathic CH or HCC.

Objectives New specialty drugs such as biologics are now available in record numbers, presenting increased safety risks for people with immune-mediated diseases. However, comprehensive assessments of patient safety for these drugs are lacking. We examined performance on key patient safety measures, such as screening for latent tuberculosis (LTBI), hepatitis B virus (HBV), and hepatitis C virus (HCV), for new users of a broad group of specialty medications. Methods Data were extracted via electronic health record data warehouses of a large university health system using structured queries, and extensive chart review was performed to confirm measure elements. We included all new users of immunosuppressive specialty drugs between 2013 and 2017. We assessed screening for LTBI, HBV, and HCV from 12 months before through 60 days after medication initiation, and calculated performance on a composite measure that required screening for all three infections. Multivariable logistic regression was used to assess differences in screening across specialties, adjusting for patient race, sex, age, and comorbidities. Results Among 2027 patients, the most common drugs prescribed were adalimumab (32%), etanercept (24%), infliximab (19%), and ustekinumab (9%). Overall, 62% of patients were screened for LTBI, 42% for HBV, and 33% for HCV. Only 26% of patients were screened appropriately for all three infections. Screening patterns differed significantly according to treating specialty. Conclusions We found gaps in ambulatory safety for patients treated with immunosuppressive specialty drugs for diverse inflammatory conditions across all relevant treating specialties. More robust safety protocols are urgently needed to prevent serious patient safety events in this high-risk population.

A disproportionate number of Greenland's Inuit population are chronically infected with Hepatitis B virus (HBV; 5–10%). HBV genotypes B and D are most prevalent in the circumpolar Arctic. Here, we report 39 novel HBV/D sequences from individuals residing in southwestern Greenland. We performed phylodynamic analyses with ancient HBV DNA calibrators to investigate the origin and relationship of these taxa to other HBV sequences. We inferred a substitution rate of 1.4 × 10−5[95% HPD 8.8 × 10−6, 2.0 × 10−5] and a time to the most recent common ancestor of 629 CE [95% HPD 37–1138 CE]. The Greenland taxa form a sister clade to HBV/D2 sequences, specifically New Caledonian and Indigenous Taiwanese sequences. The Greenland sequences share amino acid signatures with subgenotypes D1 and D2 and ~97% sequence identity. Our results suggest the classification of these novel sequences does not fit within the current nomenclature. Thus, we propose these taxa be considered a novel quasi-subgenotype.

BackgroundVaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts.MethodsWe applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres.ResultsUsing both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response.ConclusionThis study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.

N6-methyladenosine (m(6)A) RNA methylation is the most abundant epitranscriptomic modification of eukaryotic messenger RNAs (mRNAs). Previous reports have found m(6)A on both cellular and viral transcripts and defined its role in regulating numerous biological processes, including viral infection. Here, we show that m(6)A and its associated machinery regulate the life cycle of hepatitis B virus (HBV). HBV is a DNA virus that completes its life cycle via an RNA intermediate, termed pregenomic RNA (pgRNA). Silencing of enzymes that catalyze the addition of m(6)A to RNA resulted in increased HBV protein expression, but overall reduced reverse transcription of the pgRNA. We mapped the m(6)A site in the HBV RNA and found that a conserved m(6)A consensus motif situated within the epsilon stem loop structure, is the site for m(6)A modification. The epsilon stem loop is located in the 3′ terminus of all HBV mRNAs and at both the 5′ and 3′ termini of the pgRNA. Mutational analysis of the identified m(6)A site in the 5′ epsilon stem loop of pgRNA revealed that m(6)A at this site is required for efficient reverse transcription of pgRNA, while m(6)A methylation of the 3′ epsilon stem loop results in destabilization of all HBV transcripts, suggesting that m(6)A has dual regulatory function for HBV RNA. Overall, this study reveals molecular insights into how m(6)A regulates HBV gene expression and reverse transcription, leading to an increased level of understanding of the HBV life cycle.

Hepatitis B reactivation associated with immune suppressive and biological therapies is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to hepatitis B virus infection. The population at risk for HBV reactivation includes those who are either currently infected with HBV or have past exposure to HBV. Since curative and eradicative therapy for HBV is not currently available, there is a large reservoir of individuals at risk for HBV reactivation in the general population. HBV reactivation with its potential consequences is particularly a concern when these people are exposed to either cancer chemotherapy, immunosuppressive or biologic therapies for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid organ or bone marrow transplantation. With the advent of newer and emerging forms of targeted biologic therapies, it has become important to understand the mechanisms whereby certain therapies are more prone to HBV reactivation. The aim of this review is to provide a comprehensive update on the current concepts, risk factors, molecular mechanisms, prevention and management of hepatitis B reactivation. In addition, we provide recommendations for future research in this area.

Background: In the United States, Korean immigrants experience a disproportionately high burden of chronic hepatitis B (HBV) viral infection and associated liver cancer compared with the general population. However, despite clear clinical guidelines, HBV serologic testing among Koreans remains persistently suboptimal. Methods: We conducted a cluster-randomized trial to evaluate a church-based small group intervention to improve HBV testing among Koreans in Los Angeles. Fifty-two Korean churches, stratified by size (small, medium, large) and location (Koreatown versus other), were randomized to intervention or control conditions. Intervention church participants attended a single-session small-group discussion on liver cancer and HBV testing, and control church participants attended a similar session on physical activity and nutrition. Outcome data consisted of self-reported HBV testing obtained via 6-month telephone follow-up interviews. Results: We recruited 1,123 individuals, 18 to 64 years of age, across the 52 churches. Ninety-two percent of the sample attended the assigned intervention session and 86% completed the 6-month follow-up. Sample characteristics included were as follows: mean age 46 years, 65% female, 97% born in Korea, 69% completed some college, and 43% insured. In an intent-to-treat analysis, the intervention produced a statistically significant effect (OR = 4.9, P < 0.001), with 19% of intervention and 6% of control group participants reporting a HBV test. Conclusion: Our intervention was successful in achieving a large and robust effect in a population at high risk of HBV infection and sequelae. Impact: The intervention was fairly resource efficient and thus has high potential for replication in other high-risk Asian groups. Cancer Epidemiol Biomarkers Prev; 24(9); 1341–9. ©2015 AACR.

Background: Although hepatitis A virus (HAV) and hepatitis B virus (HBV) infections are vaccine-preventable diseases, few homeless parolees coming out of prisons and jails have received the hepatitis A and B vaccination series. Objectives: The study focused on completion of the HAV and HBV vaccine series among homeless men on parole. The efficacy of three levels of peer coaching (PC) and nurse-delivered interventions was compared at 12-month follow-up: (a) intensive peer coaching and nurse case management (PC-NCM); (b) intensive PC intervention condition, with minimal nurse involvement; and (c) usual care (UC) intervention condition, which included minimal PC and nurse involvement. Furthermore, we assessed predictors of vaccine completion among this targeted sample. Methods: A randomized control trial was conducted with 600 recently paroled men to assess the impact of the three intervention conditions (PC-NCM vs. PC vs. UC) on reducing drug use and recidivism; of these, 345 seronegative, vaccine-eligible subjects were included in this analysis of completion of the Twinrix HAV/HBV vaccine. Logistic regression was added to assess predictors of completion of the HAV/HBV vaccine series and chi-square analysis to compare completion rates across the three levels of intervention. Results: Vaccine completion rate for the intervention conditions were 75.4% (PC-NCM), 71.8% (PC), and 71.9% (UC; p = .78). Predictors of vaccine noncompletion included being Asian and Pacific Islander, experiencing high levels of hostility, positive social support, reporting a history of injection drug use, being released early from California prisons, and being admitted for psychiatric illness. Predictors of vaccine series completion included reporting having six or more friends, recent cocaine use, and staying in drug treatment for at least 90 days. Discussion: Findings allow greater understanding of factors affecting vaccination completion in order to design more effective programs among the high-risk population of men recently released from prison and on parole.

Reactivation of hepatitis B in the context of immunosuppressive therapy may be severe and potentially fatal. The US Food and Drug Administration has recently drawn attention to the potentially fatal risk of hepatitis B reactivation in patients receiving the anti-CD20 agents ofatumumab or rituximab. This action focuses attention on the broader issue of hepatitis B virus reactivation, which may occur with a wide variety of immunosuppressive therapies in benign or malignant disease. This article summarizes the data behind this issue. These data support the recommendation that all patients undergoing chemotherapy, immunosuppressive therapy, hematopoietic stem cell transplantation, or solid organ transplantation be screened for active or prior hepatitis B viral infection by testing for hepatitis B surface antigen and the antibody to hepatitis B core antigen in serum. Those who are found to be hepatitis B surface antigen–positive should start appropriate antiviral therapy to prevent reactivation. Additionally, even those who have recovered from hepatitis B will benefit from antiviral therapy in certain circumstances because of the risks associated with a form of hepatitis B virus reactivation referred to as “reverse seroconversion.” There remain many uncertain areas that warrant further study, and further advances will benefit from close interactions between various medical specialties, regulatory agencies, and researchers. Conclusions: There is good evidence to support routine screening of all patients for hepatitis B prior to undergoing chemotherapy or immunosuppressive treatment; use of prompt antiviral treatment appears to diminish the risk of severe or fatal reactivation of hepatitis B. (Hepatology 2015;61:703-711)

The aim of this study was to evaluate the effectiveness of an educational method of providing viral hepatitis education for methadone maintenance patients. Four hundred forty participants were randomly assigned to either a control or a motivationally-enhanced viral hepatitis education and counseling intervention. Viral hepatitis A (HAV), B (HBV), and C (HCV) knowledge tests were administered at baseline, following each of two education sessions (post-education), and at a 3-month follow-up assessment. Results indicated a significant increase in knowledge of HAV, HBV, and HCV over time. No differences were found in knowledge between the intervention groups in knowledge acquisition regarding any of the hepatitis viruses suggesting that a motivational interviewing style may not augment hepatitis knowledge beyond standard counseling. A two-session viral hepatitis education intervention effectively promotes hepatitis knowledge and can be integrated in methadone treatment settings. © 2014 Elsevier Inc.

With a yearly death toll of 880,000, hepatitis B virus (HBV) remains a major health problem worldwide, despite an effective prophylactic vaccine and well-tolerated, effective antivirals. HBV causes chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The viral genome persists in infected hepatocytes even after long-term antiviral therapy, and its integration, though no longer able to support viral replication, destabilizes the host genome. HBV is a DNA virus that utilizes a virus-encoded reverse transcriptase to convert an RNA intermediate, termed pregenomic RNA, into the relaxed circular DNA genome, which is subsequently converted into a covalently closed circular DNA (cccDNA) in the host cell nucleus. cccDNA is maintained in the nucleus of the infected hepatocyte as a stable minichromosome and functions as the viral transcriptional template for the production of all viral gene products, and thus, it is the molecular basis of HBV persistence. The nuclear cccDNA pool can be replenished through recycling of newly synthesized, DNA-containing HBV capsids. Licensed antivirals target the HBV reverse transcriptase activity but fail to eliminate cccDNA, which would be required to cure HBV infection. Elimination of HBV cccDNA is so far only achieved by antiviral immune responses. Thus, this review will focus on possible curative strategies aimed at eliminating or crippling the viral cccDNA. Newer insights into the HBV life cycle and host immune response provide novel, potentially curative therapeutic opportunities and targets.