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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 -
Clinics in Liver Disease Aug 2023Acute-on-chronic liver failure (ACLF) is a potentially reversible syndrome that develops in patients with cirrhosis or with underlying chronic liver disease (CLD) and is... (Review)
Review
Acute-on-chronic liver failure (ACLF) is a potentially reversible syndrome that develops in patients with cirrhosis or with underlying chronic liver disease (CLD) and is characterized by acute decompensation, organ failure, and high short-term mortality. Hepatitis A and hepatitis E are major causes of ACLF. Hepatitis B may also cause ACLF through a flare of hepatitis B, acute infection, or reactivation. Besides supportive care, nucleoside/nucleotide analog therapy should also be initiated in this setting. Nonhepatotropic viruses may rarely also cause ACLF with the severe acute respiratory syndrome coronavirus 2 virus recently being identified with poorer outcomes in those with underlying CLD.
Topics: Humans; Acute-On-Chronic Liver Failure; COVID-19; Hepatitis B; Hepatitis E; Liver Cirrhosis
PubMed: 37380286
DOI: 10.1016/j.cld.2023.03.006 -
World Journal of Gastroenterology Feb 2022Viral hepatitis is a significant health problem worldwide, associated with morbidity and mortality. Hepatitis B, C, D, and occasionally E viruses (HBV, HCV, HDV, and... (Review)
Review
Viral hepatitis is a significant health problem worldwide, associated with morbidity and mortality. Hepatitis B, C, D, and occasionally E viruses (HBV, HCV, HDV, and HEV) can evolve in chronic infections, whereas hepatitis A virus (HAV) frequently produces acute self-limiting hepatitis. In the last years, different studies have been performed to introduce new antiviral therapies. The most important goal in the treatment of viral hepatitis is to avoid chronic liver disease and complications. This review analyzes currently available therapies, in particular for viruses associated with chronic liver disease. The focus is especially on HBV and HCV therapies, investigating new drugs already introduced in clinical practice and clinical trials. We also describe new entry inhibitors, developed for the treatment of chronic HDV and HBV and currently available treatments for HEV. The last drugs introduced have shown important efficacy in HCV, with achievable target HCV elimination by 2030. Concurrently, renewed interest in curative HBV therapies has been registered; current nucleotide/nucleoside analogs positively impact liver-related complications, ensuring high safety and tolerability. Novel approaches to HBV cure are based on new antivirals, targeting different steps of the HBV life cycle and immune modulators. The improved knowledge of the HDV life cycle has facilitated the development of some direct-acting agents, as bulevirtide, the first drug conditionally approved in Europe for HDV associated compensated liver disease. Further studies are required to identify a new therapeutic approach in hepatitis E, especially in immunosuppressed patients.
Topics: Hepatitis B; Hepatitis B virus; Hepatitis, Viral, Human; Humans; Lipopeptides; Motivation
PubMed: 35316960
DOI: 10.3748/wjg.v28.i5.517 -
Journal of Hepatology Mar 2020Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic HBV... (Review)
Review
Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic HBV treatment endpoints to guide clinical trials aiming to 'cure' HBV. Agreement among the conference participants was reached on some key points. 'Functional' but not sterilising cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment. The primary endpoint of phase III trials should be functional cure; HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity for the prediction of sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg-positive or negative chronic hepatitis, who are treatment-naïve or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with an increase in bilirubin or international normalised ratio should prompt temporary or permanent cessation of an investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase III trials for HDV coinfection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalisation of alanine aminotransferase is considered an intermediate goal. In conclusion, regarding HBV 'functional cure', the primary goal is sustained HBsAg loss with undetectable HBV DNA after completion of treatment and the intermediate goal is sustained undetectable HBV DNA without HBsAg loss after stopping treatment.
Topics: Alanine Transaminase; Antiviral Agents; Biomarkers; Clinical Trials, Phase III as Topic; Coinfection; DNA, Viral; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis D, Chronic; Hepatitis Delta Virus; Humans; Research Design; Sustained Virologic Response
PubMed: 31730789
DOI: 10.1016/j.jhep.2019.11.003 -
Frontiers in Cellular and Infection... 2023Viral hepatitis is a major worldwide public health issue, affecting hundreds of millions of people and causing substantial morbidity and mortality. The majority of the... (Review)
Review
Viral hepatitis is a major worldwide public health issue, affecting hundreds of millions of people and causing substantial morbidity and mortality. The majority of the worldwide burden of viral hepatitis is caused by five biologically unrelated hepatotropic viruses: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Metabolomics is an emerging technology that uses qualitative and quantitative analysis of easily accessible samples to provide information of the metabolic levels of biological systems and changes in metabolic and related regulatory pathways. Alterations in glucose, lipid, and amino acid levels are involved in glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, and amino acid metabolism. These changes in metabolites and metabolic pathways are associated with the pathogenesis and medication mechanism of viral hepatitis and related diseases. Additionally, differential metabolites can be utilized as biomarkers for diagnosis, prognosis, and therapeutic responses. In this review, we present a thorough overview of developments in metabolomics for viral hepatitis.
Topics: Humans; Hepatitis, Viral, Human; Hepatitis B virus; Hepatitis C; Hepatitis E virus; Hepacivirus
PubMed: 37265499
DOI: 10.3389/fcimb.2023.1189417 -
International Journal of Molecular... Jun 2023The hepatitis A virus (HAV) infection causes acute hepatitis. HAV also induces acute liver failure or acute-on-chronic liver failure; however, no potent anti-HAV drugs...
The hepatitis A virus (HAV) infection causes acute hepatitis. HAV also induces acute liver failure or acute-on-chronic liver failure; however, no potent anti-HAV drugs are currently available in clinical situations. For anti-HAV drug screening, more convenient and useful models that mimic HAV replication are needed. In the present study, we established HuhT7-HAV/Luc cells, which are HuhT7 cells stably expressing the HAV HM175-18f genotype IB subgenomic replicon RNA harboring the firefly luciferase gene. This system was made by using a PiggyBac-based gene transfer system that introduces nonviral transposon DNA into mammalian cells. Then, we investigated whether 1134 US Food and Drug Administration (FDA)-approved drugs exhibited in vitro anti-HAV activity. We further demonstrated that treatment with tyrosine kinase inhibitor masitinib significantly reduced both HAV HM175-18f genotype IB replication and HAV HA11-1299 genotype IIIA replication. Masitinib also significantly inhibited HAV HM175 internal ribosomal entry-site (IRES) activity. In conclusion, HuhT7-HAV/Luc cells are adequate for anti-HAV drug screening, and masitinib may be useful for the treatment of severe HAV infection.
Topics: Humans; Hepatitis A; Hepatitis A Antibodies; Hepatitis A virus; Protein Biosynthesis; RNA, Viral; Virus Replication; Subgenomic RNA
PubMed: 37298659
DOI: 10.3390/ijms24119708 -
Journal of Viral Hepatitis Oct 2022Viral hepatitis is caused by a heterogenous group of viral agents representing a wide range of phylogenetic groups. Many viruses can involve the liver and cause liver... (Review)
Review
Viral hepatitis is caused by a heterogenous group of viral agents representing a wide range of phylogenetic groups. Many viruses can involve the liver and cause liver injury but only a subset are delineated as 'hepatitis viruses' based upon their primary site of replication and tropism for hepatocytes which make up the bulk of the liver cell population. Since their discovery, beginning with the agent that caused serum hepatitis in the 1960s, the alphabetic designations have been utilized. To date, we have five hepatitis viruses, A through E, though it is postulated that others may exist. This chapter will focus on those viruses. Note that hepatitis D is included as a subset of hepatitis B, as it cannot exist without concurrent hepatitis B infection. Pregnancy has the potential to affect all aspects of these viral agents due to the unique immunologic and physiologic changes that occur during and after the gestational period. In this review, we will discuss the most common viral hepatitis and their effects during pregnancy.
Topics: Female; Hepatitis B; Hepatitis D; Hepatitis Viruses; Hepatitis, Viral, Human; Humans; Phylogeny; Pregnancy; Pregnancy Complications, Infectious
PubMed: 35748741
DOI: 10.1111/jvh.13725 -
Current Pharmaceutical Design 2021Viral hepatitis in pregnancy constitutes a complex issue, requiring meticulous management due to the potential potent compromise of both mother's and fetus' health.... (Review)
Review
Viral hepatitis in pregnancy constitutes a complex issue, requiring meticulous management due to the potential potent compromise of both mother's and fetus' health. Hepatitis B and C are implicated with a high risk for chronicity, whereas hepatitis A and hepatitis E have an acute course. In pre-existing viral disease, pregnancy may lead to exacerbation of the disease's course due to a plethora of hormonal, immunological and genetic alterations. Vice versa, viral hepatitis, acute or chronic, during pregnancy, can cause gestational complications that may lead to significant maternal and neonatal morbidity and mortality. Mother to child transmission of hepatitis B and C virus, in high prevalence areas, has been recognized as a major cause of chronic viral infection and related complications in children. Due to the physiologic alterations in pregnancy, therapeutic indications may differ from those in the general population and there is an expanding field of research on available drugs and vaccines efficacy and safety during pregnancy. Of utmost importance remains the implementation of a preventive strategy in order to reduce the rates of vertical transmission. Universal screening of pregnant women, assessing the risk of transmission and determining the mode of delivery and the impact of breastfeeding are crucial aspects of this strategy. This review summarizes the impact of viral hepatitis in pregnancy, strategies of prevention of vertical transmission and available treatments.
Topics: Child; Female; Hepatitis B; Hepatitis B virus; Hepatitis, Viral, Human; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious
PubMed: 33302848
DOI: 10.2174/1381612826666201210113841 -
Bundesgesundheitsblatt,... Feb 2022
Topics: Germany; Hepatitis, Viral, Human; Humans
PubMed: 35015107
DOI: 10.1007/s00103-021-03485-9 -
Clinical Obstetrics and Gynecology Mar 2020Infectious hepatitis in pregnancy is clinically significant in both the acute and chronic phases. Here, we review the perinatal implications of chronic hepatitis B and C... (Review)
Review
Infectious hepatitis in pregnancy is clinically significant in both the acute and chronic phases. Here, we review the perinatal implications of chronic hepatitis B and C and acute hepatitis A and E. Familiarity with screening, transmission, diagnosis, and management of infectious hepatitis is of ongoing importance during obstetric care, as these diseases are endemic in much of the world. Pregnancy and interpregnancy care provide opportunities to prevent infection and transmission of hepatitis.
Topics: Antiviral Agents; Female; Hepatitis, Viral, Human; Humans; Infectious Disease Transmission, Vertical; Postnatal Care; Pregnancy; Pregnancy Complications, Infectious
PubMed: 31895116
DOI: 10.1097/GRF.0000000000000512