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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 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 -
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 -
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 Dec 2020Hepatitis C virus (HCV) is an important human pathogen with a high chronicity rate. An estimated 71 million people worldwide are living with chronic hepatitis C (CHC)... (Review)
Review
Hepatitis C virus (HCV) is an important human pathogen with a high chronicity rate. An estimated 71 million people worldwide are living with chronic hepatitis C (CHC) infection, which carries the risk of progression to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Similar to other RNA viruses, HCV has a high rate of genetic variability generated by its high mutation rate and the actions of evolutionary forces over time. There are two levels of HCV genetic variability: intra-host variability, characterized by the distribution of HCV mutant genomes present in an infected individual, and inter-host variability, represented by the globally circulating viruses that give rise to different HCV genotypes and subtypes. HCV genetic diversity has important implications for virus persistence, pathogenesis, immune responses, transmission, and the development of successful vaccines and antiviral strategies. Here we will discuss how HCV genetic heterogeneity impacts viral spread and therapeutic control.
Topics: Antiviral Agents; Clinical Decision-Making; Disease Management; Drug Resistance, Viral; Genetic Variation; Genome, Viral; Genotype; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Quasispecies; RNA, Viral; Virus Replication
PubMed: 33383891
DOI: 10.3390/v13010041 -
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 -
Viruses Jun 2023According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are four main... (Review)
Review
According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are four main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans via undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection, and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.
Topics: Animals; Humans; Hepatitis E virus; Molecular Epidemiology; Hepatitis E; Zoonoses; Hepatitis, Chronic; Genotype
PubMed: 37376687
DOI: 10.3390/v15061389 -
Nature Reviews. Gastroenterology &... Aug 2022In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the... (Review)
Review
In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
Topics: Antiviral Agents; Carcinoma, Hepatocellular; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Liver Neoplasms
PubMed: 35595834
DOI: 10.1038/s41575-022-00608-8 -
Gastroenterology Jan 2023The hepatitis B virus (HBV) is a major cause of cirrhosis and hepatocellular carcinoma worldwide. Despite an effective vaccine, the prevalence of chronic infection... (Review)
Review
The hepatitis B virus (HBV) is a major cause of cirrhosis and hepatocellular carcinoma worldwide. Despite an effective vaccine, the prevalence of chronic infection remains high. Current therapy is effective at achieving on-treatment, but not off-treatment, viral suppression. Loss of hepatitis B surface antigen, the best surrogate marker of off-treatment viral suppression, is associated with improved clinical outcomes. Unfortunately, this end point is rarely achieved with current therapy because of their lack of effect on covalently closed circular DNA, the template of viral transcription and genome replication. Major advancements in our understanding of HBV virology along with better understanding of immunopathogenesis have led to the development of a multitude of novel therapeutic approaches with the prospect of achieving functional cure (hepatitis B surface antigen loss) and perhaps complete cure (clearance of covalently closed circular DNA and integrated HBV DNA). This review will cover current best practice for managing chronic HBV infection and emerging novel therapies for HBV infection and their prospect for cure.
Topics: Humans; Hepatitis B Surface Antigens; Antiviral Agents; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; DNA, Circular; Liver Neoplasms; DNA, Viral; Virus Replication
PubMed: 36243037
DOI: 10.1053/j.gastro.2022.10.008