Comparative efficacy of double plasma molecular adsorption system combined with plasma exchange versus plasma exchange in treating acute-on-chronic liver failure due to hepatitis B: A meta-analysis.

This meta-analysis aims to evaluate the effectiveness of the double plasma molecular adsorption system (DPMAS) in combination with plasma exchange (PE) compared to plasma exchange alone in the treatment of Acute-on-Chronic liver failure (LF) caused by hepatitis B. Until August 31, 2023, a comprehensive search of databases including Embase, Chinese Medical Journal Full-text Database, China Biomedical Literature Database, Wan Fang Medical Network, PubMed, and the Cochrane Library was carried out using keywords like "liver failure," "acute-on-chronic liver failure," "PE," "DPMAS," and related terms. The quality of the included studies was evaluated using QUADS (quality assessment of diagnostic accuracy studies). Software Revman 5.3 was used to examine the data, while Stata 15.1 was used to run Egger's test. Following thorough screening, 452 patients who received PE alone and 429 patients who received DPMAS in addition to PE were included. Every study that was included was of a high caliber. When comparing the DPMAS plus PE group to the PE alone group, the total bilirubin reduction was considerably higher (mean difference [MD] = -49.09, 95% confidence interval [CI]: -54.84 to -43.35, p < .00001). Prothrombin activity (PTA; MD = -1.53, 95% CI: -3.29 to -0.22, p = .09), albumin (ALB; MD = -0.58, 95% CI: -1.57 to 0.41, p = .25), prothrombin time (PT; MD = -0.07, 95% CI: -1.47 to 1.34, p = .92), and platelet count (PLT; MD = -0.08, 95% CI: -1.33 to 1.66, p = .90) did not differ significantly. The improvement in international standardized ratio (INR) was significantly greater in the PE group (MD = 0.07, 95% CI (0.03, 0.10), p = .0001). When combined with DPMAS, PE has been shown to be more effective in lowering total bilirubin levels. PE can also lower INR in individuals who have hepatitis B-related ACLF. This therapeutic strategy also lessens the need for plasma transfusions.

[Expert recommendations on screening, testing and management for hepatitis B virus infection in adults].

The prevalence of hepatitis B represents a significant public health concern with a heavy disease burden. In China, there is still a big gap between the current diagnosis and treatment rates of hepatitis B and the goal of eliminating viral hepatitis as a public health threat by 2030 set by the World Health Organization (WHO). In order to achieve the WHO goal and the goal of 2030 Healthy China Outline, the Chinese Preventive Medicine Association organized domestic experts in the fields of clinical medicine, public health and clinical laboratory medicine to develop the Expert Recommendations on Screening, Testing and Management for Hepatitis B Virus Infection in Adults after several rounds of discussion based on comprehensive review of relevant domestic and international guidelines and literatures, the purpose is to facilitate universal screening of hepatitis B virus(HBV)infection in adults and provide practical guidance on disease assessment, treatment and long-term follow-up management of people infected with HBV and vaccination for people susceptible to HBV infection,thus promoting the elimination of the threat of hepatitis B.

Development of monoclonal antibodies to target the large surface protein of hepatitis B virus and their use in therapeutic and diagnostic applications.

Over 250 million people are living with chronic infection caused by the hepatitis B virus (HBV). HBV has three surface proteins, namely small (SHBs), medium (MHBs) and large (LHBs), and they play different roles in the virus life cycle. The approved hepatitis B vaccine only contains the SHBs protein and many studies have focused on characterising the functional domains in SHBs. Although the LHBs protein is less studied, recent studies have shown that it plays important roles in mediating viral entry, replication and assembly. Over the years, there have been major advancements in monoclonal antibody (mAb) discovery tools and multiple mAbs have been developed to specifically target the preS1 domain in LHBs. We summarise the HBV infection systems and antibody discovery strategies that have been utilised by various research groups to assess the potential use of anti-preS1 mAbs as therapeutic antibodies against HBV or in the development of new diagnostic assays.

Hepatitis D virus infection: Progress on the path toward disease control and cure.

This article discusses the impact of Hepatitis D virus (HDV) infection as a major cause of liver-related morbidity and mortality in people with Hepatitis B virus (HBV) infection. The article reviews the current knowledge and unanswered questions about the epidemiology, pathogenesis, and natural history of HDV infection. Although effective treatments for HDV infection have been elusive, interferon alfa is recommended for at least 48 weeks. However, response rates with standard-of-care peginterferon alfa are suboptimal, leading to few patients with a sustained virologic response. The article proposes novel approaches to treating HDV and HBV, including targeting reduction or loss of hepatitis B surface antigen (HBsAg) reduction, and discusses potential strategies for achieving HBsAg loss in patients with chronic HBV infection. Finally, the article discusses the landmark decision of accepting viral and biochemical surrogates by regulatory authorities, opening the door for the clinical development of drugs for patients with HDV infection.

Cost-effectiveness of treating all hepatitis B-positive individuals in the United States.

Chronic hepatitis B virus (HBV) infection is a leading cause of liver disease and related mortality globally. However, most of the infected individuals in the United States remain undiagnosed and untreated. There is a need to understand more completely the economic and disease burden impact of removing treatment restrictions and increasing diagnosis and treatment. The PRoGReSs model, a dynamic HBV model that tracks the infected population by year, disease stage, and gender, was used to quantify the disease and economic burden of chronic HBV infection in the United States from 2020 to 2050 based on four scenarios: a status quo (base) scenario and three treat-all scenarios, in which screening, diagnosis, and treatment were maximized at different annual treatment price levels of $5382, $2000 and $750. Compared to the base scenario, the treat-all scenarios would avert 71,100 acute and 11,100 chronic incident cases of HBV, and 169,000 liver-related deaths from 2020 to 2050. At an annual treatment cost of $2000, treating all HBV infections would be highly cost-effective, and at $750 would be cost saving and would achieve a positive return on investment before 2050. Maximizing the diagnosed and treated HBV population in the United States would avert a significant number of cases of advanced liver disease and related mortality. Such interventions can also be cost-effective compared to the status quo strategy, and cost saving at a treatment price threshold of $750 annually, above the current lowest annual treatment cost of $362.

Safety and efficacy of double plasma molecular adsorption system with sequential low-volume plasma exchange in intermediate-stage hepatitis B virus-related acute-on-chronic liver failure.

Current evidence suggests that the mortality rate of intermediate-stage hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remains high. We aimed to investigate the safety and efficacy of double plasma molecular adsorption system (DPMAS) with sequential low-volume plasma exchange (LPE) treatment in intermediate-stage HBV-related ACLF. This prospective study recruited intermediate-stage HBV-related ACLF patients and was registered on ClinicalTrials.gov (NCT04597164). Eligible patients were randomly divided into a trial group and a control group. Patients in both groups received comprehensive medical treatment. Patients in the trial group further received DPMAS with sequential LPE. Data were recorded from baseline to Week 12. Fifty patients with intermediate-stage HBV-related ACLF were included in this study. The incidence of bleeding events and allergic reactions in the trial group was 12% and 4%, respectively, with no other treatment-related adverse events. The levels of total bilirubin and prothrombin time-international normalized ratio, and model for end-stage liver disease scores after each session of DPMAS with sequential LPE were significantly lower than those before treatment (all p < 0.05). The 12-week cumulative liver transplantation-free survival rates in the trial and control groups were 52% and 24%, respectively (p = 0.041). The 12-week cumulative overall survival rates in the trial and control groups were 64% and 36%, respectively (p = 0.048). The Kaplan-Meier survival analysis revealed significant differences in liver transplantation-free survival (p = 0.047) and overall survival (p = 0.038) between the trial and control groups. Cox regression analysis indicated that blood urea nitrogen (p = 0.038), DPMAS with sequential LPE (p = 0.048), and Chinese Group on the Study of Severe Hepatitis B-ACLF II score (p < 0.001) were significant risk factors for mortality. DPMAS with sequential LPE treatment is safe and effective for patients with intermediate-stage HBV-related ACLF.

The viral hepatitis B care cascade: A population-based comparison of immigrant groups.

BACKGROUND AND AIMS: The global burden of viral hepatitis B is substantial, and monitoring infections across the care cascade is important for elimination efforts. There is little information on care disparities by immigration status, and we aimed to quantify disease burden among immigrant subgroups. APPROACH AND RESULTS: In this population-based, retrospective cohort study, we used linked laboratory and health administrative records to describe the HBV care cascade in five distinct stages: (1) lifetime prevalence; (2) diagnosis; (3) engagement with care; (4) treatment initiation; and (5) treatment continuation. Infections were identified based on at least one reactive antigen or nucleic acid test, and lifetime prevalence was estimated as the sum of diagnosed and estimated undiagnosed cases. Care cascades were compared between long-term residents and immigrant groups, including subgroups born in hepatitis B endemic countries. Stratified analyses and multivariable Poisson regression were used to identify drivers for cascade progression. Between January 1997 and December 2014, 2,014,470 persons were included, 50,475 with infections, of whom 30,118 were engaged with care, 11,450 initiated treatment, and 6554 continued treatment >1 year. Lifetime prevalence was estimated as 163,309 (1.34%) overall, 115,722 (3.42%) among all immigrants, and 50,876 (9.37%) among those from highly endemic countries. Compared to long-term residents, immigrants were more likely to be diagnosed (adjusted rate ratio [aRR], 4.55; 95% CI, 4.46, 4.63), engaged with care (aRR, 1.07; 95% CI, 1.04, 1.09), and initiate treatment (aRR, 1.09; 95% CI, 1.03, 1.16). CONCLUSIONS: In conclusion, immigrants fared well compared to long-term residents along the care cascade, having higher rates of diagnosis and slightly better measures in subsequent cascade stages, although intensified screening efforts and better strategies to facilitate linkage to care are still needed.

Targeting the hepatitis B cccDNA with a sequence-specific ARCUS nuclease to eliminate hepatitis B virus in vivo.

Persistence of chronic hepatitis B (CHB) is attributed to maintenance of the intrahepatic pool of the viral covalently closed circular DNA (cccDNA), which serves as the transcriptional template for all viral gene products required for replication. Current nucleos(t)ide therapies for CHB prevent virus production and spread but have no direct impact on cccDNA or expression of viral genes. We describe a potential curative approach using a highly specific engineered ARCUS nuclease (ARCUS-POL) targeting the hepatitis B virus (HBV) genome. Transient ARCUS-POL expression in HBV-infected primary human hepatocytes produced substantial reductions in both cccDNA and hepatitis B surface antigen (HBsAg). To evaluate ARCUS-POL in vivo, we developed episomal adeno-associated virus (AAV) mouse and non-human primate (NHP) models containing a portion of the HBV genome serving as a surrogate for cccDNA. Clinically relevant delivery was achieved through systemic administration of lipid nanoparticles containing ARCUS-POL mRNA. In both mouse and NHP, we observed a significant decrease in total AAV copy number and high on-target indel frequency. In the case of the mouse model, which supports HBsAg expression, circulating surface antigen was durably reduced by 96%. Together, these data support a gene-editing approach for elimination of cccDNA toward an HBV cure.

Feasibility and acceptability of integrating hepatitis B care into routine HIV services: a qualitative study among health care providers and patients in West Nile region, Uganda.

BACKGROUND: Despite facing a dual burden of HBV and HIV, Africa lacks experience in offering integrated care for HIV and HBV. To contextualize individual and group-level feasibility and acceptability of an integrated HIV/HBV care model, we explored perspectives of health care providers and care recipients on feasibility and acceptability of integration. METHODS: In two regional hospitals of West Nile region, we performed a demonstration project to assess feasibility and acceptability of merging the care of HBV-monoinfected patients with existing HIV care system. Using interviews with health care providers as key informants, and 6 focus groups discussions with 3 groups of patients, we explored feasibility [(i)whether integration is perceived to fit within the existing healthcare infrastructure, (ii) perceived ease of implementation of HIV/HBV integrated care, and (iii) perceived sustainability of integration] and acceptability [whether the HIV/HBV care model is perceived as (i) suitable, (ii) satisfying and attractive (iii) there is perceived demand, need and intention to recommend its use]. We audio-recorded the interviews and data was analysed using framework analysis. RESULTS: The following themes emerged from the data (i) integrating HBV into HIV care is perceived to be feasible, fit and beneficial, after making requisite adjustments (ii) integration is acceptable due to the need for both free treatment and anticipated collaboration between HIV and HBV clients in terms of peer-support (iii) there are concerns about the likely rise in stigma and the lack of community awareness about integrated care. CONCLUSION: The integrated HIV/HBV care model is feasible and acceptable among both providers and recipients. Necessary adjustments to the existing care system, including training, for community sensitization on the reasons and significance of integration are required.

Training the healthcare workforce: the global experience with telementorship for hepatitis B and hepatitis C.

BACKGROUND: Telementorship has emerged as an innovative strategy to decentralise medical knowledge and increase healthcare capacity across a wide range of disease processes. We report the global experience with telementorship to support healthcare workers delivering hepatitis B virus (HBV) and hepatitis C virus (HCV) care and treatment. METHODS: In early 2020, we conducted a survey of HBV and HCV telementorship programmes, followed by an in-depth interview with programme leads. Programmes were eligible to participate if they were located outside of the United States (U.S.), focused on support to healthcare workers in management of HBV and/or HCV, and were affiliated with or maintained adherence to the Project ECHO model, a telementorship programme pioneered at the University of New Mexico. One programme in the U.S., focused on HCV treatment in the Native American community, was purposively sampled and invited to participate. Surveys were administered online, and all qualitative interviews were performed remotely. Descriptive statistics were calculated for survey responses, and qualitative interviews were assessed for major themes. RESULTS: Eleven of 18 eligible programmes completed the survey and follow up interview. Sixty-four percent of programmes were located at regional academic medical centers. The majority of programmes (64%) were led by hepatologists. Most programmes (82%) addressed both HBV and HCV, and the remainder focused on HCV only. The median number of participating clinical spoke sites per programme was 22, and most spoke site participants were primary care providers. Most ECHO sessions were held monthly (36%) or bimonthly (27%), with sessions ranging from 45 min to 2 h in length. Programme leaders identified collective learning, empowerment and collaboration to be key strengths of their telementorship programme, while insufficient funding and a lack of protected time for telementorship leaders and participants were identified as major barriers to success. CONCLUSION: The Project ECHO model for telementorship can be successfully implemented across high and low-and-middle-income countries to improve provider knowledge and experience in management of viral hepatitis. There is a tremendous opportunity to further expand upon the existing experience with telementorship to support non-specialist healthcare workers and promote elimination of viral hepatitis.

Health workers' perspectives of hepatitis B-related stigma among Aboriginal and Torres Strait Islander people in New South Wales, Australia.

BACKGROUND: Experiences of stigma and discrimination can act as a significant barrier to testing, monitoring, and treatment for hepatitis B virus (HBV). Aboriginal and Torres Strait Islander Australians are a population disproportionately impacted by HBV and yet limited research has explored HBV-related stigma in these communities. To begin preliminary explorations of HBV-related stigma among Aboriginal and Torres Strait Islander people, we interviewed health workers about their perceptions regarding HBV infection and HBV-related stigma. METHODS: Participants were recruited from staff involved in the Deadly Liver Mob (DLM) program which is a health promotion program that offers incentives for Aboriginal and Torres Strait Islander clients to be educated on viral hepatitis, recruit and educate peers, and receive screening and treatment for blood-borne viruses (BBVs) and sexually transmissible infections (STIs), and vaccination. Semi-structured interviews were conducted with 11 Aboriginal and Torres Strait Islander and non-Aboriginal or Torres Strait Islander health workers who have been involved in the development, implementation, and/or management of the DLM program within participating services in New South Wales, Australia. RESULTS: Findings suggest that stigma is a barrier to accessing mainstream health care among Aboriginal and Torres Strait Islander clients, with stigma being complex and multi-layered. Aboriginal and Torres Strait Islander people contend with multiple and intersecting layers of stigma and discrimination in their lives, and thus HBV is just one dimension of those experiences. Health workers perceived that stigma is fuelled by multiple factors, including poor HBV health literacy within the health workforce broadly and among Aboriginal and Torres Strait Islander clients, shame about social practices associated with viral hepatitis, and fear of unknown transmission risks and health outcomes. The DLM program was viewed as helping to resist and reject stigma, improve health literacy among both health workers and clients, and build trust and confidence in mainstream health services. CONCLUSIONS: Health promotion programs have the potential to reduce stigma by acting as a 'one stop shop' for BBVs and STIs through one-on-one support, yarning, and promotion of the HBV vaccine, monitoring for chronic HBV, and treatment (where required).

[Challenges in accessing treatment for chronic hepatitis B in Madagascar : A qualitative study of caregivers and patients]. / Enjeux et difficultés de l'accès aux traitements pour la prise en charge de l'hépatite B chronique à Madagascar : étude qualitative auprès des soignants et personnes atteintes.

OBJECTIVES: Madagascar faces many difficulties in accessing diagnosis and treatment of hepatitis B. The prevalence of chronic hepatitis B infection is estimated at 6.9%. The costs associated with screening and treatment are high and not easily accessible. This article proposes a reflection on the challenges and difficulties of access to diagnosis and treatment for patients with chronic hepatitis B. METHOD: The "Neo Vac" study aimed to document the life paths of people living with chronic hepatitis B, their difficulties and their perceptions of HBV. Twenty-three semi-structured interviews were conducted in 2019 in Antananarivo with patients and gastroenterologists. RESULTS: The study describes the numerous obstacles that mark the therapeutic pathways of chronic HBV patients. The first result indicates lack of knowledge of the disease by chronic HBV patients and the varied circumstances in which the disease is discovered. None of the persons interviewed had been screened on their own initiative, the screening having taken place during prenatal consultations or emergency hospitalizations or during a morbidity episode. The care pathway was characterized by doubt and anxiety due to lack of knowledge about the possible disease outcome and concern about the costs of care. DISCUSSION: Little known by the population and health professionals, hepatitis B is rarely the subject of voluntary screening and is most often detected during an apparently unrelated health event. The exorbitant cost of treatment for patients, the cost of medical analyses and secondary costs, and the unavailability of follow-up tests outside the capital constitute barriers to access to care that are insurmountable for the majority of the Malagasy population. CONCLUSIONS: This first qualitative study on the experiences of HBV-infected persons in terms of access to care and treatment in Madagascar underlines the extent to which access to treatment remains limited, due to the absence of a national policy for the prevention, screening and management of hepatitis B, which remains a highly neglected and unrecognized disease in Madagascar as well as internationally.

A Model of Care Optimized for Marginalized Remote Population Unravels Migration Pattern in India.

BACKGROUND AND AIMS: Access to basic health needs remains a challenge for most of world's population. In this study, we developed a care model for preventive and disease-specific health care for an extremely remote and marginalized population in Arunachal Pradesh, the northeasternmost state of India. APPROACH AND RESULTS: We performed patient screenings, performed interviews, and obtained blood samples in remote villages of Arunachal Pradesh through a tablet-based data collection application, which was later synced to a cloud database for storage. Positive cases of hepatitis B virus (HBV) were confirmed and genotyped in our central laboratory. The blood tests performed included liver function tests, HBV serologies, and HBV genotyping. HBV vaccination was provided as appropriate. A total of 11,818 participants were interviewed, 11,572 samples collected, and 5,176 participants vaccinated from the 5 westernmost districts in Arunachal Pradesh. The overall hepatitis B surface antigen (HBsAg) prevalence was found to be 3.6% (n = 419). In total, 34.6% were hepatitis B e antigen positive (n = 145) and 25.5% had HBV DNA levels greater than 20,000 IU/mL (n = 107). Genotypic analysis showed that many patients were infected with HBV C/D recombinants. Certain tribes showed high seroprevalence, with rates of 9.8% and 6.3% in the Miji and Nishi tribes, respectively. The prevalence of HBsAg in individuals who reported medical injections was 3.5%, lower than the overall prevalence of HBV. CONCLUSIONS: Our unique, simplistic model of care was able to link a highly resource-limited population to screening, preventive vaccination, follow-up therapeutic care, and molecular epidemiology to define the migratory nature of the population and disease using an electronic platform. This model of care can be applied to other similar settings globally.

Hepatitis B virus envelope proteins can serve as therapeutic targets embedded in the host cell plasma membrane.

Hepatitis B virus (HBV) infection is a major health threat causing 880,000 deaths each year. Available therapies control viral replication but do not cure HBV, leaving patients at risk to develop hepatocellular carcinoma. Here, we show that HBV envelope proteins (HBs)-besides their integration into endosomal membranes-become embedded in the plasma membrane where they can be targeted by redirected T-cells. HBs was detected on the surface of HBV-infected cells, in livers of mice replicating HBV and in HBV-induced hepatocellular carcinoma. Staining with HBs-specific recombinant antibody MoMab recognising a conformational epitope indicated that membrane-associated HBs remains correctly folded in HBV-replicating cells in cell culture and in livers of HBV-transgenic mice in vivo. MoMab coated onto superparamagnetic iron oxide nanoparticles allowed to detect membrane-associated HBs after HBV infection by electron microscopy in distinct stretches of the hepatocyte plasma membrane. Last but not least, we demonstrate that HBs located on the cell surface allow therapeutic targeting of HBV-positive cells by T-cells either engrafted with a chimeric antigen receptor or redirected by bispecific, T-cell engager antibodies. TAKE AWAYS: HBs become translocated to the plasma membrane. Novel, recombinant antibody confirmed proper conformation of HBs on the membrane. HBs provide an interesting target by T-cell-based, potentially curative therapies.

CRISPR/Cas9 delivery by NIR-responsive biomimetic nanoparticles for targeted HBV therapy.

BACKGROUND: Currently, there are no curative drugs for hepatitis B virus (HBV). Complete elimination of HBV covalently closed circular DNA (cccDNA) is key to the complete cure of hepatitis B virus infection. The CRISPR/Cas9 system can directly destroy HBV cccDNA. However, a CRISPR/Cas9 delivery system with low immunogenicity and high efficiency has not yet been established. Moreover, effective implementation of precise remote spatiotemporal operations in CRISPR/Cas9 is a major limitation. RESULTS: In this work, we designed NIR-responsive biomimetic nanoparticles (UCNPs-Cas9@CM), which could effectively deliver Cas9 RNP to achieve effective genome editing for HBV therapy. HBsAg, HBeAg, HBV pgRNA and HBV DNA along with cccDNA in HBV-infected cells were found to be inhibited. These findings were confirmed in HBV-Tg mice, which did not exhibit significant cytotoxicity and minimal off-target DNA damage. CONCLUSIONS: The UCNPs-based biomimetic nanoplatforms achieved the inhibition of HBV replication via CRISPR therapy and it is a potential system for efficient treatment of human HBV diseases.

Hepatitis B Virus: Advances in Prevention, Diagnosis, and Therapy.

Currently, despite the use of a preventive vaccine for several decades as well as the use of effective and well-tolerated viral suppressive medications since 1998, approximately 250 million people remain infected with the virus that causes hepatitis B worldwide. Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the leading causes of liver cancer and overall mortality globally, surpassing malaria and tuberculosis. Linkage to care is estimated to be very poor both in developing countries and in high-income countries, such as the United States, countries in Western Europe, and Japan. In the United States, by CDC estimates, only one-third of HBV-infected patients or less are aware of their infection. Some reasons for these low rates of surveillance, diagnosis, and treatment include the asymptomatic nature of chronic hepatitis B until the very late stages, a lack of curative therapy with a finite treatment duration, a complex natural history, and a lack of knowledge about the disease by both care providers and patients. In the last 5 years, more attention has been focused on the important topics of HBV screening, diagnosis of HBV infection, and appropriate linkage to care. There have also been rapid clinical developments toward a functional cure of HBV infection, with novel compounds currently being in various phases of progress. Despite this knowledge, many of the professional organizations provide guidelines focused only on specific questions related to the treatment of HBV infection. This focus leaves a gap for care providers on the other HBV-related issues, which include HBV's epidemiological profile, its natural history, how it interacts with other viral hepatitis diseases, treatments, and the areas that still need to be addressed in order to achieve HBV elimination by 2030. Thus, to fill these gaps and provide a more comprehensive and relevant document to regions worldwide, we have taken a global approach by using the findings of global experts on HBV as well as citing major guidelines and their various approaches to addressing HBV and its disease burden.

Epidemiological and clinical characteristics of 70 cases of coronavirus disease and concomitant hepatitis B virus infection: A multicentre descriptive study.

The interaction between existing chronic liver diseases caused by hepatitis B virus (HBV) infection and COVID-19 has not been studied. We analysed 70 COVID-19 cases combined with HBV infection (CHI) to determine the epidemiological, clinical characteristics, treatment and outcome. We investigated clinical presentation, imaging and laboratory parameters of COVID-19 patients of seven hospitals from Jan 20 to March 20, 2020. Multivariate analysis was used to analyse risk factors for progression of patients with COVID-19 combined with HBV infection. Compared with COVID-19 without HBV infection (WHI) group, patients with dual infection had a higher proportion of severe/critically ill disease (32.86% vs. 15.27%, P = .000), higher levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and activated partial thromboplastin (APTT) [50(28-69)vs 21(14-30), P = .000; 40(25-54) vs 23(18-30), P = .000; 34.0(27.2-38.7) vs 37.2(31.1-41.4), P = .031]. The utilization rates of Arbidol and immunoglobulin were significantly higher than those in the co-infected group [48.57% vs. 35.64%, P < .05; 21.43% vs. 8.18%, P < .001], while the utilization rate of chloroquine phosphate was lower (1.43% vs 14.00%, P < .05) in the co-infected patients group. Age and c-reactive protein (CRP) level were independent risk factors for recovery of patients with COVID-19 combined with HBV infection. The original characteristics of COVID-19 cases combined with HBV infection were higher rate of liver injury, coagulation disorders, severe/critical tendency and increased susceptibility. The elderly and patients with higher level of CRP were more likely to experience a severe outcome of COVID-19.

SIRT7 restricts HBV transcription and replication through catalyzing desuccinylation of histone H3 associated with cccDNA minichromosome.

Chronic hepatitis B virus (HBV) infection is a significant public health burden worldwide. HBV covalently closed circular DNA (cccDNA) organized as a minichromosome in nucleus is responsible for viral persistence and is the key obstacle for a cure of chronic hepatitis B (CHB). Recent studies suggest cccDNA transcription is epigenetically regulated by histone modifications, especially histone acetylation and methylation. In the present study, we identified transcriptionally active histone succinylation (H3K122succ) as a new histone modification on cccDNA minichromosome by using cccDNA ChIP-Seq approach. Silent mating type information regulation 2 homolog 7 (SIRT7), as an NAD+-dependent histone desuccinylase, could bind to cccDNA through interaction with HBV core protein where it catalyzed histone 3 lysine 122 (H3K122) desuccinylation. Moreover, SIRT7 acts cooperatively with histone methyltransferase, suppressor of variegation 3-9 homolog 1 (SUV39H1) and SET domain containing 2 (SETD2) to induce silencing of HBV transcription through modulation of chromatin structure. Our data improved the understanding of histone modifications of the cccDNA minichromosome, thus transcriptional silencing of cccDNA may represent a novel antiviral strategy for the prevention or treatment of HBV infection.

Calcium signaling in hepatitis B virus infection and its potential as a therapeutic target.

As a ubiquitous second messenger, calcium (Ca2+) can interact with numerous cellular proteins to regulate multiple physiological processes and participate in a variety of diseases, including hepatitis B virus (HBV) infection, which is a major cause of hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. In recent years, several studies have demonstrated that depends on the distinct Ca2+ channels on the plasma membrane, endoplasmic reticulum, as well as mitochondria, HBV can elevate cytosolic Ca2+ levels. Moreover, within HBV-infected cells, the activation of intracellular Ca2+ signaling contributes to viral replication via multiple molecular mechanisms. Besides, the available evidence indicates that targeting Ca2+ signaling by suitable pharmaceuticals is a potent approach for the treatment of HBV infection. In the present review, we summarized the molecular mechanisms related to the elevation of Ca2+ signaling induced by HBV to modulate viral propagation and the recent advances in Ca2+ signaling as a potential therapeutic target for HBV infection. Video Abstract.

Risk of mother-to-child transmission of hepatitis B virus after fetal blood sampling: a report of six cases.

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.