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Viruses Sep 2021The hepatitis A virus (HAV) is a leading cause of acute viral hepatitis worldwide. It is transmitted mainly by direct contact with patients who have been infected or by... (Review)
Review
The hepatitis A virus (HAV) is a leading cause of acute viral hepatitis worldwide. It is transmitted mainly by direct contact with patients who have been infected or by ingesting contaminated water or food. The virus is endemic in low-income countries where sanitary and sociodemographic conditions are poor. Paradoxically, improving sanitary conditions in these countries, which reduces the incidence of HAV infections, can lead to more severe disease in susceptible adults. The populations of developed countries are highly susceptible to HAV, and large outbreaks can occur when the virus is spread by globalization and by increased travel and movement of foodstuffs. Most of these outbreaks occur among high-risk groups: travellers, men who have sex with men, people who use substances, and people facing homelessness. Hepatitis A infections can be prevented by vaccination; safe and effective vaccines have been available for decades. Several countries have successfully introduced universal mass vaccination for children, but high-risk groups in high-income countries remain insufficiently protected. The development of HAV antivirals may be important to control HAV outbreaks in developed countries where a universal vaccination programme is not recommended.
Topics: Antiviral Agents; Disease Outbreaks; Hepatitis A; Hepatitis A virus; Homosexuality, Male; Humans; Incidence; Male; Risk Factors; Sexual and Gender Minorities; Travel
PubMed: 34696330
DOI: 10.3390/v13101900 -
The Lancet. Gastroenterology &... Apr 2023The 69th World Health Assembly endorsed the global health sector strategy on viral hepatitis to eliminate viral hepatitis as a public health threat by 2030. Achieving...
BACKGROUND
The 69th World Health Assembly endorsed the global health sector strategy on viral hepatitis to eliminate viral hepatitis as a public health threat by 2030. Achieving and measuring the 2030 targets requires a substantial increase in the capacity to test and treat viral hepatitis infections and a mechanism to monitor the progress of hepatitis elimination. This study aimed to identify the gaps in data availability or quality and create a new mechanism to monitor the progress of hepatitis elimination.
METHODS
In 2020, using a questionnaire, we collected empirical, systematic, modelled, or surveyed data-reported by WHO country and WHO regional offices-on indicators of progress towards elimination of viral hepatitis, including burden of infection, incidence, mortality, and the cascade of care, and validated these data.
FINDINGS
WHO received officially validated country-provided data from 130 countries or territories, and used partner-provided data for 70 countries or territories. We estimated that in 2019, globally, 295·9 million (3·8%) people were living with chronic hepatitis B virus (HBV) infection and 57·8 million (0·8%) people were living with chronic hepatitis C virus (HCV) infection. Globally, there were more than 3·0 million new infections with HBV and HCV and more than 1·1 million deaths due to the viruses in 2019. In 2019, 30·4 million (95% CI 24·3-38·0) individuals living with hepatitis B knew their infection status and 6·6 million (5·3-8·3) people diagnosed with hepatitis B received treatment. Among people with HCV infection, 15·2 million (95% CI 12·1-19·0) had been diagnosed between 2015 and 2019, and 9·4 million (7·5-11·7) people diagnosed with hepatitis C infection were treated with direct-acting antiviral drugs between 2015 and 2019.
INTERPRETATION
There has been notable global progress towards hepatitis elimination. In 2019, 30·4 million (10·3%) people living with hepatitis B knew their infection status, which was slightly higher than in 2015 (22·0 million; 9·0%), and 6·6 million (22·7%) of those diagnosed with hepatitis B received treatment, compared with 1·7 million (8·0%) in 2015. Mortality from hepatitis C has declined since 2019, driven by an increase in HCV treatment ten times that of the strategy baseline. However, an estimated 89·7% of HBV infections and 78·6% of HCV infections remain undiagnosed. A new global strategy for 2022-30, based on these new estimates, should be implemented urgently to scale up the screening and treatment of viral hepatitis.
FUNDING
World Health Organization.
Topics: Humans; Hepatitis B, Chronic; Hepatitis C, Chronic; Antiviral Agents; Hepatitis C; Hepatitis B; Hepacivirus; Hepatitis, Viral, Human; Hepatitis A
PubMed: 36764320
DOI: 10.1016/S2468-1253(22)00386-7 -
American Family Physician Oct 2021Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. The incidence of infection in the United States decreased by more than... (Review)
Review
Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. The incidence of infection in the United States decreased by more than 90% after an effective vaccine was introduced, but the number of cases has been increasing because of large community outbreaks in unimmunized individuals. Classic symptoms include fever, malaise, dark urine, and jaundice and are more common in older children and adults. People are most infectious 14 days before and seven days after the development of jaundice. Diagnosis of acute infection requires the use of serologic testing for immunoglobulin M anti-hepatitis A antibodies. The disease is usually self-limited, supportive care is often sufficient for treatment, and chronic infection or chronic liver disease does not occur. Routine hepatitis A immunization is recommended in children 12 to 23 months of age. Immunization is also recommended for individuals at high risk of contracting the infection, such as persons who use illegal drugs, those who travel to areas endemic for hepatitis A, incarcerated populations, and persons at high risk of complications from hepatitis A, such as those with chronic liver disease or HIV infection. The vaccine is usually recommended for pre- and postexposure prophylaxis, but immune globulin can be used in patients who are too young to be vaccinated or if the vaccine is contraindicated.
Topics: Adolescent; Adult; Alanine Transaminase; Child; Child, Preschool; Hepatitis A; Hepatitis A Vaccines; Humans; Infant; Middle Aged; Post-Exposure Prophylaxis; Risk Factors; Young Adult
PubMed: 34652109
DOI: No ID Found -
Cold Spring Harbor Perspectives in... Dec 2019Evidence for the existence of another hepatitis-causing pathogen, other than the known hepatitis A and B viruses, emerged in the mid-1970s. A frustrating search of 15... (Review)
Review
Evidence for the existence of another hepatitis-causing pathogen, other than the known hepatitis A and B viruses, emerged in the mid-1970s. A frustrating search of 15 years was ended by the identification of the hepatitis C virus in 1989 using a recombinant DNA immunoscreening method. This discovery quickly led to blood tests that eliminated posttransfusion hepatitis C and could show the partial efficacy of type 1 interferon-based therapies. Subsequent knowledge of the viral replication cycle then led to the development of effective direct-acting antivirals targeting its serine protease, polymerase, and nonstructural protein 5A that resulted in the approval of orally available drug combinations that can cure patients within a few months with few side effects. Meanwhile, vaccine strategies have been shown to be feasible, and they are still required to effectively control this global epidemic.
Topics: Animals; Antiviral Agents; Drug Discovery; Epidemics; Hepacivirus; Hepatitis C, Chronic; Host-Pathogen Interactions; Humans; Life Cycle Stages; Viral Hepatitis Vaccines
PubMed: 31501269
DOI: 10.1101/cshperspect.a037069 -
Viruses Apr 2023Hepatitis A and hepatitis E are relatively common causes of liver disease. Both viruses are mainly transmitted through the faecal-oral route and, consequently, most... (Review)
Review
Hepatitis A and hepatitis E are relatively common causes of liver disease. Both viruses are mainly transmitted through the faecal-oral route and, consequently, most outbreaks occur in countries with poor sanitation. An important role of the immune response as the driver of liver injury is also shared by the two pathogens. For both the hepatitis A (HAV) and hepatitis E (HEV) viruses, the clinical manifestations of infection mainly consist of an acute disease with mild liver injury, which results in clinical and laboratory alterations that are self-limiting in most cases. However, severe acute disease or chronic, long-lasting manifestations may occur in vulnerable patients, such as pregnant women, immunocompromised individuals or those with pre-existing liver disease. Specifically, HAV infection rarely results in fulminant hepatitis, prolonged cholestasis, relapsing hepatitis and possibly autoimmune hepatitis triggered by the viral infection. Less common manifestations of HEV include extrahepatic disease, acute liver failure and chronic HEV infection with persistent viraemia. In this paper, we conduct a non-systematic review of the available literature to provide a comprehensive understanding of the state of the art. Treatment mainly consists of supportive measures, while the available evidence for aetiological treatment and additional agents in severe disease is limited in quantity and quality. However, several therapeutic approaches have been attempted: for HAV infection, corticosteroid therapy has shown outcome improvement, and molecules, such as AZD 1480, zinc chloride and heme oxygenase-1, have demonstrated a reduction in viral replication in vitro. As for HEV infection, therapeutic options mainly rely on the use of ribavirin, and some studies utilising pegylated interferon-alpha have shown conflicting results. While a vaccine for HAV is already available and has led to a significant reduction in the prevalence of the disease, several vaccines for HEV are currently being developed, with some already available in China, showing promising results.
Topics: Humans; Female; Pregnancy; Hepatitis A; Hepatitis E; Hepatitis E virus; Acute Disease
PubMed: 37243166
DOI: 10.3390/v15051080 -
Obstetrics and Gynecology Sep 2023The purpose of this document is to describe the specific types of viral hepatitis, their implications during pregnancy, the risk of perinatal transmission, and issues...
PURPOSE
The purpose of this document is to describe the specific types of viral hepatitis, their implications during pregnancy, the risk of perinatal transmission, and issues related to both treatment and prevention of infection.
TARGET POPULATION
Pregnant or postpartum women and individuals who screen positive for viral hepatitis infection. The onset of these conditions may have predated the perinatal period or may have occurred for the first time in pregnancy or the first year postpartum.
METHODS
This guideline was developed using an a priori protocol in conjunction with a writing team consisting of one specialist in obstetrics and gynecology appointed by the ACOG Committee on Clinical Practice Guidelines-Obstetrics and one external subject matter expert. ACOG medical librarians completed a comprehensive literature search for primary literature within Cochrane Library, Cochrane Collaboration Registry of Controlled Trials, EMBASE, PubMed, and MEDLINE. Studies that moved forward to the full-text screening stage were assessed by two authors from the writing team based on standardized inclusion and exclusion criteria. Included studies underwent quality assessment, and a modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) evidence-to-decision framework was applied to interpret and translate the evidence into recommendation statements.
RECOMMENDATIONS
This Clinical Practice Guideline includes recommendations on hepatitis B virus and hepatitis C virus screening in pregnancy; prepregnancy, antepartum, intrapartum, and postpartum management for patients with hepatitis B virus infection or hepatitis C virus infection; management of accidental and occupational exposure to hepatitis B virus or hepatitis C virus in pregnant health care workers; and hepatitis A virus and hepatitis B virus vaccination in pregnancy. Recommendations are classified by strength and evidence quality. Ungraded Good Practice Points are included to provide guidance when a formal recommendation could not be made because of inadequate or nonexistent evidence.
Topics: Female; Humans; Pregnancy; Gynecology; Hepacivirus; Hepatitis B; Hepatitis C; Infectious Disease Transmission, Vertical; Postpartum Period
PubMed: 37590986
DOI: 10.1097/AOG.0000000000005300 -
Gastroenterology Clinics of North... Jun 2020Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections are common and are associated with a variety of liver manifestations. EBV and CMV infections, in... (Review)
Review
Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections are common and are associated with a variety of liver manifestations. EBV and CMV infections, in immunocompetent hosts, commonly manifest as acute hepatitis, with severity varying from asymptomatic, self-limited icteric hepatitis to acute liver failure. Atypical manifestations, such as cholestasis, chronic hepatitis, precipitation of acute-on-chronic liver failure, and autoimmune hepatitis, are reported with EBV infection, whereas cholestasis, portal vein thrombosis, and Budd-Chiari syndrome are reported with CMV infection. In the setting of liver transplantation, CMV is the most common infectious complication and carries significant morbidity; EBV is the major cause of post-transplant lymphoproliferative disorders.
Topics: Cytomegalovirus Infections; Epstein-Barr Virus Infections; Hepatitis, Viral, Human; Humans; Immunocompromised Host; Liver Transplantation; Lymphoproliferative Disorders; Postoperative Complications
PubMed: 32389366
DOI: 10.1016/j.gtc.2020.01.008 -
Virulence Dec 2021Hepatitis A is an acute infection of the liver, which is mostly asymptomatic in children and increases the severity with age. Although in most patients the infection... (Review)
Review
Hepatitis A is an acute infection of the liver, which is mostly asymptomatic in children and increases the severity with age. Although in most patients the infection resolves completely, in a few of them it may follow a prolonged or relapsed course or even a fulminant form. The reason for these different outcomes is unknown, but it is generally accepted that host factors such as the immunological status, age and the occurrence of underlaying hepatic diseases are the main determinants of the severity. However, it cannot be ruled out that some virus traits may also contribute to the severe clinical outcomes. In this review, we will analyze which genetic determinants of the virus may determine virulence, in the context of a paradigmatic virus in terms of its genomic, molecular, replicative, and evolutionary features.
Topics: Child; Hepatitis A; Hepatitis A virus; Humans; Virulence
PubMed: 33843464
DOI: 10.1080/21505594.2021.1910442 -
Viruses May 2021Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain... (Review)
Review
Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain incompletely understood. As the replication of HAV is noncytopathic in vitro, a widely accepted concept has been that virus-specific cytotoxic T cells are responsible for liver injury. However, accumulating evidence suggests that natural killer (NK) cells, NKT cells, and even non-HAV-specific CD8 T cells contribute to liver damage during HAV infection. In addition, intrinsic death of virus-infected hepatocytes has been implicated as a cause of liver injury in a murine model of hepatitis A. Furthermore, genetic variations in host factors such as T cell immunoglobulin-1 (TIM1) and IL-18 binding protein (IL-18BP) have been linked to hepatitis A severity. This review summarizes the current knowledge of the mechanisms of hepatocellular injury in hepatitis A. Different mechanisms may be involved under different conditions and they are not necessarily mutually exclusive. A better understanding of these mechanisms would aid in diagnosis and treatment of diseases associated with HAV infection.
Topics: Animals; Carcinoma, Hepatocellular; Hepatitis A; Hepatitis A virus; Hepatocytes; Humans; Liver; Liver Neoplasms; Mice
PubMed: 34066709
DOI: 10.3390/v13050861 -
Gut Sep 2021Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an... (Review)
Review
Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an unfavourable outcome, with many patients developing liver cirrhosis, liver failure and eventually hepatocellular carcinoma within 5-10 years. The identification of the HBV/HDV receptor and the development of novel in vitro and animal infection models allowed a more detailed study of the HDV life cycle in recent years, facilitating the development of specific antiviral drugs. The characterisation of HDV-specific CD4+ and CD8+T cell epitopes in untreated and treated patients also permitted a more precise understanding of HDV immunobiology and possibly paves the way for immunotherapeutic strategies to support upcoming specific therapies targeting viral or host factors. Pegylated interferon-α has been used for treating HDV patients for the last 30 years with only limited sustained responses. Here we describe novel treatment options with regard to their mode of action and their clinical effectiveness. Of those, the entry-inhibitor bulevirtide (formerly known as myrcludex B) received conditional marketing authorisation in the European Union (EU) in 2020 (Hepcludex). One additional drug, the prenylation inhibitor lonafarnib, is currently under investigation in phase III clinical trials. Other treatment strategies aim at targeting hepatitis B surface antigen, including the nucleic acid polymer REP2139Ca. These recent advances in HDV virology, immunology and treatment are important steps to make HDV a less difficult-to-treat virus and will be discussed.
Topics: Adaptive Immunity; Animals; Hepatitis D; Hepatitis D, Chronic; Hepatitis Delta Virus; Humans; Immunity, Innate
PubMed: 34103404
DOI: 10.1136/gutjnl-2020-323888