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Clinical Microbiology Reviews Mar 2020Currently, 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,... (Review)
Review
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.
Topics: Antiviral Agents; Clinical Laboratory Techniques; Coinfection; HIV; Hepacivirus; Hepatitis B; Hepatitis B virus; Humans; United States
PubMed: 32102898
DOI: 10.1128/CMR.00046-19 -
American Family Physician Mar 2019Hepatitis B virus (HBV) is a partly double-stranded DNA virus that causes acute and chronic liver infection. Screening for hepatitis B is recommended in pregnant women...
Hepatitis B virus (HBV) is a partly double-stranded DNA virus that causes acute and chronic liver infection. Screening for hepatitis B is recommended in pregnant women at their first prenatal visit and in adolescents and adults at high risk of chronic infection. Hepatitis B vaccination is recommended for medically stable infants weighing 2,000 g or more within 24 hours of birth, unvaccinated infants and children, and unvaccinated adults requesting protection from hepatitis B or who are at increased risk of infection. Acute hepatitis B is defined as the discrete onset of symptoms, the presence of jaundice or elevated serum alanine transaminase levels, and test results showing hepatitis B surface antigen and hepatitis B core antigen. There is no evidence that antiviral treatment is effective for acute hepatitis B. Chronic hepatitis B is defined as the persistence of hepatitis B surface antigen for more than six months. Individuals with chronic hepatitis B are at risk of hepatocellular carcinoma and cirrhosis, but morbidity and mortality are reduced with adequate treatment. Determining the stage of liver disease (e.g., evidence of inflammation, fibrosis) is important to guide therapeutic decisions and the need for surveillance for hepatocellular carcinoma. Treatment should be individualized based on clinical and laboratory characteristics and the risks of developing cirrhosis and hepatocellular carcinoma. Immunologic cure, defined as the loss of hepatitis B surface antigen with sustained HBV DNA suppression, is attainable with current drug therapies that suppress HBV DNA replication and improve liver inflammation and fibrosis. Pegylated interferon alfa-2a, entecavir, and tenofovir are recommended as first-line treatment options for chronic hepatitis B.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Hepatitis B; Humans; Pregnancy; Pregnancy Complications
PubMed: 30811163
DOI: No ID Found -
Viruses Jul 2022Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable... (Review)
Review
Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Many advances have been made in clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. OBI is diffused worldwide, but its prevalence is highly variable among patient populations. This depends on different geographic areas, risk factors for parenteral infections, and assays used for HBsAg and HBV DNA detection. OBI has an impact in several clinical contexts: (a) it can be transmitted, causing a classic form of hepatitis B, through blood transfusion or liver transplantation; (b) it may reactivate in the case of immunosuppression, leading to the possible development of even fulminant hepatitis; (c) it may accelerate the progression of chronic liver disease due to different causes toward cirrhosis; (d) it maintains the pro-oncogenic properties of the "overt" infection, favoring the development of hepatocellular carcinoma.
Topics: DNA, Viral; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Neoplasms
PubMed: 35891484
DOI: 10.3390/v14071504 -
International Journal of Molecular... Dec 2020Chronic hepatitis B virus (HBV) infection is a major global health problem. It can cause progressive liver fibrosis leading to cirrhosis with end-stage liver disease,... (Review)
Review
Chronic hepatitis B virus (HBV) infection is a major global health problem. It can cause progressive liver fibrosis leading to cirrhosis with end-stage liver disease, and a markedly increased risk of hepatocellular carcinoma. In the last two decades, substantial progress has been made in the treatment of chronic hepatitis, B. However, HBV is often reactivated after stopping nucloes(t)ide analogues because antivirals alone do not directly target covalently closed circular DNA, which is the template for all viral RNAs. Therefore, although currently available antiviral therapies achieve suppression of HBV replication in the majority of patients, hepatitis B surface antigen (HBsAg) loss and seroconversion is rarely achieved despite long-term antiviral treatment (HBsAg loss of less than 10% in 5 years). Various clinical trials of agents that interrupt the HBV life cycle in hepatocytes have been conducted. Potential treatment strategies and new agents are emerging as HBV cure. A combination of current and new anti-HBV agents may increase the rate of HBsAg seroclearance; thus, optimized regimens must be validated. Here, we review the newly investigated therapeutic compounds and the results of preclinical and/or clinical trials.
Topics: Antiviral Agents; Hepatitis B; Hepatitis B virus; Humans; Molecular Targeted Therapy
PubMed: 33379331
DOI: 10.3390/ijms22010213 -
World Journal of Gastroenterology Jul 2021Hepatitis B virus (HBV) is the leading cause of chronic viral hepatitis. Annually, almost two million children younger than 5 years acquire the infection, mostly through... (Review)
Review
Hepatitis B virus (HBV) is the leading cause of chronic viral hepatitis. Annually, almost two million children younger than 5 years acquire the infection, mostly through vertical or horizontal transmission in early life. Vertical transmission of HBV is a high efficacy phenomenon ranging, in the absence of any preventive interventions, from 70% to 90% for hepatitis e antigen positive mothers and from 10% to 40% for hepatitis e antigen-negative mothers. Maternal viraemia is a preeminent risk factor for vertical transmission of HBV. Maternal screening is the first step to prevent vertical transmission of HBV. Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection. Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low- and middle-income countries where the prevalence of the infection is at the highest.
Topics: Antiviral Agents; Child; Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Vaccines; Hepatitis B e Antigens; Hepatitis B virus; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious
PubMed: 34326618
DOI: 10.3748/wjg.v27.i26.4182 -
Viruses Nov 2020In this Special Issue, we have brought together a broad range of studies on hepatitis B virus (HBV) covering diagnosis, pathogenesis, monitoring, and treatment [...].
In this Special Issue, we have brought together a broad range of studies on hepatitis B virus (HBV) covering diagnosis, pathogenesis, monitoring, and treatment [...].
Topics: Disease Management; Disease Susceptibility; Hepatitis B; Hepatitis B virus; Humans
PubMed: 33265922
DOI: 10.3390/v12121366 -
Cold Spring Harbor Perspectives in... Oct 2014It is now 50 years since the discovery of the hepatitis B virus (HBV), and, despite the availability of a prophylactic vaccine for more than 20 years, HBV infection... (Review)
Review
It is now 50 years since the discovery of the hepatitis B virus (HBV), and, despite the availability of a prophylactic vaccine for more than 20 years, HBV infection remains a disease of significant global health burden. It is estimated that more than 240 million people are chronically infected with HBV and, therefore, are at risk for the development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). The risk of clinical complications has traditionally been higher in older males with hepatitis B e antigen (HBeAg)-positive disease, high-grade liver necroinflammation, and progressive fibrosis. Recent advances in the understanding of the natural history of chronic HBV infection have identified an important role for plasma HBV DNA levels as a marker of risk for clinical outcomes. Among adults, persistent high-level HBV replication is associated with an increased risk of cirrhosis, as well as HCC development. This has led to the therapeutic focus on achieving sustained viral suppression. There is an emerging role for quantitative hepatitis B surface antigen (HBsAg) levels as a marker of natural history. Low levels of HBsAg have been associated with sustained immune control, HBsAg seroclearance, as well as lower risk of HCC. In this work, we review the natural history of HBV infection, with a focus on the determinants of clinical outcomes in patients with chronic hepatitis B (CHB) infection.
Topics: Coinfection; HIV Infections; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Humans; Risk Factors
PubMed: 25359547
DOI: 10.1101/cshperspect.a024935 -
Virology May 2015Human hepatitis B virus (HBV) is the prototype of a family of small DNA viruses that productively infect hepatocytes, the major cell of the liver, and replicate by... (Review)
Review
Human hepatitis B virus (HBV) is the prototype of a family of small DNA viruses that productively infect hepatocytes, the major cell of the liver, and replicate by reverse transcription of a terminally redundant viral RNA, the pregenome. Upon infection, the circular, partially double-stranded virion DNA is converted in the nucleus to a covalently closed circular DNA (cccDNA) that assembles into a minichromosome, the template for viral mRNA synthesis. Infection of hepatocytes is non-cytopathic. Infection of the liver may be either transient (<6 months) or chronic and lifelong, depending on the ability of the host immune response to clear the infection. Chronic infections can cause immune-mediated liver damage progressing to cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of carcinogenesis are unclear. Antiviral therapies with nucleoside analog inhibitors of viral DNA synthesis delay sequelae, but cannot cure HBV infections due to the persistence of cccDNA in hepatocytes.
Topics: Carcinoma, Hepatocellular; Chronic Disease; DNA, Viral; Hepatitis B; Hepatitis B virus; Host-Pathogen Interactions; Humans; Liver Cirrhosis; RNA, Messenger; RNA, Viral; Reverse Transcription; Virus Replication
PubMed: 25759099
DOI: 10.1016/j.virol.2015.02.031 -
Nature Reviews. Gastroenterology &... Nov 2022Globally, 296 million people are infected with hepatitis B virus (HBV), and approximately one million people die annually from HBV-related causes, including liver... (Review)
Review
Globally, 296 million people are infected with hepatitis B virus (HBV), and approximately one million people die annually from HBV-related causes, including liver cancer. Although there is a preventative vaccine and antiviral therapies suppressing HBV replication, there is no cure. Intensive efforts are under way to develop curative HBV therapies. Currently, only a few biomarkers are available for monitoring or predicting HBV disease progression and treatment response. As new therapies become available, new biomarkers to monitor viral and host responses are urgently needed. In October 2020, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) held a virtual and interactive workshop on HBV biomarkers endorsed by the International HBV Meeting. Various stakeholders from academia, clinical practice and the pharmaceutical industry, with complementary expertise, presented and participated in panel discussions. The clinical utility of both classic and emerging viral and immunological serum biomarkers with respect to the course of infection, disease progression, and response to current and emerging treatments was appraised. The latest advances were discussed, and knowledge gaps in understanding and interpretation of HBV biomarkers were identified. This Roadmap summarizes the strengths, weaknesses, opportunities and challenges of HBV biomarkers.
Topics: Humans; Hepatitis B virus; Hepatitis B, Chronic; Antiviral Agents; Virus Replication; Biomarkers; Disease Progression; Hepatitis B
PubMed: 35859026
DOI: 10.1038/s41575-022-00649-z -
Journal of Hepatology Dec 2014Hepatitis B flare, defined as an event with abrupt rise of alanine aminotransferase (ALT) levels to >5 times the upper limit of normal during chronic hepatitis B virus... (Review)
Review
Hepatitis B flare, defined as an event with abrupt rise of alanine aminotransferase (ALT) levels to >5 times the upper limit of normal during chronic hepatitis B virus (HBV) infection, is considered to be the result of a human leukocyte antigen-I restricted, cytotoxic T lymphocyte mediated immune response against HBV and its downstream mechanisms. It may occur spontaneously, during or after antiviral therapy and in the setting of immunosuppression and/or chemotherapy. The clinical spectrum of hepatitis B flares varies from asymptomatic to symptomatic and typical overt acute hepatitis, even with hepatic decompensation or failure. Flares may also occur in viraemic patients with cirrhosis with higher incidence of decompensation/mortality, hence requiring immediate antiviral therapy. An upsurge of serum HBV DNA and hepatitis B surface antigen levels usually precedes the abrupt rise of ALT levels. Rising or stable and high HBV DNA during flares represent ineffective immune clearance and further hepatocytolysis, even hepatic decompensation, may occur. Such patients require immediate antiviral therapy. In contrast, bridging hepatic necrosis and/or alpha-fetoprotein levels >100 ng/ml or decreasing HBV DNA during flares represent a more effective immune clearance and frequently leads to seroclearance of HBV DNA and/or hepatitis B e antigen with remission. If patients are non-cirrhotic and there is no concern of developing decompensation, patients may be observed for 3-6 months before deciding on the need of antiviral therapy. Severe and repeated flares are prone to develop into decompensation or lead to the development of cirrhosis, thus a timely treatment to prevent the hepatitis B flare is better than to cope with the flare. Screening, monitoring and prophylactic or pre-emptive antiviral therapy is mandatory for patients who are going to receive immunosuppressants or chemotherapy.
Topics: Alanine Transaminase; Antiviral Agents; DNA, Viral; Disease Management; Disease Progression; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Mass Screening
PubMed: 25178562
DOI: 10.1016/j.jhep.2014.08.033