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Viruses Apr 2021Hepatitis viruses and liver-stage malaria are within the liver infections causing higher morbidity and mortality rates worldwide. The highly restricted tropism of the... (Review)
Review
Hepatitis viruses and liver-stage malaria are within the liver infections causing higher morbidity and mortality rates worldwide. The highly restricted tropism of the major human hepatotropic pathogens-namely, the human hepatitis B and C viruses and the and parasites-has hampered the development of disease models. These models are crucial for uncovering the molecular mechanisms underlying the biology of infection and governing host-pathogen interaction, as well as for fostering drug development. Bioengineered cell models better recapitulate the human liver microenvironment and extend hepatocyte viability and phenotype in vitro, when compared with conventional two-dimensional cell models. In this article, we review the bioengineering tools employed in the development of hepatic cell models for studying infection, with an emphasis on 3D cell culture strategies, and discuss how those tools contributed to the level of recapitulation attained in the different model layouts. Examples of host-pathogen interactions uncovered by engineered liver models and their usefulness in drug development are also presented. Finally, we address the current bottlenecks, trends, and prospect toward cell models' reliability, robustness, and reproducibility.
Topics: Animals; Bioengineering; Cell Culture Techniques; Disease Models, Animal; Disease Susceptibility; Drug Discovery; Hepatitis; Hepatitis, Viral, Human; Hepatocytes; Host-Pathogen Interactions; Humans; Liver; Liver Diseases, Parasitic
PubMed: 33925701
DOI: 10.3390/v13050773 -
Best Practice & Research. Clinical... Oct 2020Viral hepatitis can cause significant maternal and neonatal morbidity and mortality. Hepatitis A and E mainly present as acute hepatitis during pregnancy, while... (Review)
Review
Viral hepatitis can cause significant maternal and neonatal morbidity and mortality. Hepatitis A and E mainly present as acute hepatitis during pregnancy, while hepatitis C and D are usually found as chronic infection in pregnant women. Hepatitis A remains self-limiting during pregnancy while hepatitis E has a higher prevalence and manifests with a rigorous course in pregnant women. Screening of hepatitis C during pregnancy and its subsequent management during pregnancy are still a debatable topic. New treatments of hepatitis C and E require further evaluation for use in pregnancy. This review summarizes the prevalence, clinical manifestations, maternal, foetal and neonatal effects, and the management of hepatitis A, C, D and E viral infection during pregnancy.
Topics: Female; Hepatitis A; Hepatitis C; Hepatitis D; Hepatitis E; Humans; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; Prevalence
PubMed: 32305262
DOI: 10.1016/j.bpobgyn.2020.03.009 -
Viruses Jan 2023Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination... (Review)
Review
Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination is evident in the control of serious viral infections, such as smallpox and polio. Viruses that infect human livers are known as hepatitis viruses and are classified into five major types from A to E, alphabetically. Although infection with hepatitis A virus (HAV) is known to be self-resolving after rest and symptomatic treatment, there were 7134 deaths from HAV worldwide in 2016. In 2019, hepatitis B virus (HBV) and hepatitis C virus (HCV) resulted in an estimated 820,000 and 290,000 deaths, respectively. Hepatitis delta virus (HDV) is a satellite virus that depends on HBV for producing its infectious particles in order to spread. The combination of HDV and HBV infection is considered the most severe form of chronic viral hepatitis. Hepatitis E virus (HEV) is another orally transmitted virus, common in low- and middle-income countries. In 2015, it caused 44,000 deaths worldwide. Safe and effective vaccines are already available to prevent hepatitis A and B. Here, we review the recent advances in protective vaccines against the five major hepatitis viruses.
Topics: Humans; Hepatitis Viruses; Hepatitis A; Hepatitis C; Hepatitis B; Hepatitis B virus; Hepatitis A virus; Hepatitis Delta Virus; Vaccines
PubMed: 36680254
DOI: 10.3390/v15010214 -
Microbiology and Immunology Sep 2021An estimated 8-10 million people suffer from viral hepatitis in Egypt. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the major causes of viral hepatitis in... (Review)
Review
An estimated 8-10 million people suffer from viral hepatitis in Egypt. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the major causes of viral hepatitis in Egypt as 50% or more of the Egyptian population are already exposed to HAV infection by the age of 15. In addition, over 60% of the Egyptian population test seropositive for anti-HEV in the first decade of life. HEV mainly causes self-limiting hepatitis; however, cases of fulminant hepatitis and liver failure were reported in Egypt. Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are the main causes of chronic hepatitis, liver cirrhosis, and liver cancer (hepatocellular carcinoma [HCC]) in Egypt. Globally, Egypt had the highest age-standardized death rate due to cirrhosis from 1990 to 2017. The prevalence rate of HBV (1.3%-1.5%) has declined after national infantile immunization. Coinfection of HBV patients with HDV is common in Egypt because HDV antibodies (IgG) vary in range from 8.3% to 43% among total HBV patients. After the conduction of multiple national programs to control HCV infection, a lower rate of HCV prevalence (4.6%) was recently reported. Data about the incidence of HCV after treatment with direct antiviral agents (DAAs) are lacking. An HCC incidence of 29/1000/year in cirrhotic patients after DAA treatment is reported. A higher rate of infiltrative pattern among HCC patients after DAA treatment is also recognized. Viral hepatitis is one of the major public health concerns in Egypt that needs more attention and funding from health policymakers.
Topics: Antiviral Agents; Carcinoma, Hepatocellular; Egypt; Hepatitis B; Hepatitis, Viral, Human; Humans; Liver Neoplasms
PubMed: 33990999
DOI: 10.1111/1348-0421.12916 -
Journal of Applied Microbiology Nov 2020Food contaminated by hepatitis A virus (HAV) is responsible of the 2-7% of all HAV outbreaks worldwide. This review provides a description of the HAV characteristics,... (Review)
Review
Food contaminated by hepatitis A virus (HAV) is responsible of the 2-7% of all HAV outbreaks worldwide. This review provides a description of the HAV characteristics, its infectivity and epidemiological features. In addition, this review compiles existing original papers reporting HAV prevalence, viral titres in foodstuffs and the risk associated with food contamination. The purpose of this revision is to conduct a structured and systematic review of the published molecular procedures for HAV detection in food, including the assessment of its infectivity.
Topics: Disease Outbreaks; Food Contamination; Food Microbiology; Foodborne Diseases; Hepatitis A; Hepatitis A virus; Humans; Prevalence; Risk Assessment
PubMed: 32471014
DOI: 10.1111/jam.14727 -
Recent Advances in Inflammation &... 2023Hepatitis E is viral hepatitis caused by infection with the hepatitis E virus (HEV). This article aims to review HEV disease and recent advances in the management of... (Review)
Review
Hepatitis E is viral hepatitis caused by infection with the hepatitis E virus (HEV). This article aims to review HEV disease and recent advances in the management of hepatitis E. We used PubMed Clinical Queries and keywords of "hepatitis E", "hepatitis E virus" AND "zoonosis" as the search engine. "Therapy", "Clinical Prediction Guides", "Diagnosis", "Etiology" and "Prognosis" were used as filters, and "Narrow" scope was used. The search was conducted in April 2022. The information retrieved from the above search was used in the compilation of the present article. Hepatitis E is viral hepatitis caused by infection with the hepatitis E virus (HEV). Hepatitis E has mainly a fecal-oral transmission route. Hepatitis E infection usually follows an acute and self-limiting course of illness with low death rates in resource-rich areas; however, it can be more severe in pregnant women and immunocompromised people. The mortality rates in these groups are substantially higher. A vaccine for HEV is available but is not universally approved. Ribavirin remains the most efficacious medication for the treatment of HEV but is contraindicated in pregnancy. Sofosbuvir and pegylated interferon, with or without ribavirin, have not been shown in the latest literature reviews to provide reliable additional benefits to the treatment of hepatitis. Sofosbuvir should not be used as monotherapy for HEV. Food is an important source of infection in many countries while rats are the primary vector in developing nations. Management must include an understanding of the rat habitats for this zoonotic disease. Hepatitis E remains an important cause of hepatitis and a zoonotic disease globally. Public health policies are key to containing this viral infectious disease, including policy in the transfusion of blood products.
Topics: Animals; Female; Humans; Pregnancy; Rats; Hepatitis A; Hepatitis E; Hepatitis E virus; Ribavirin; Sofosbuvir; Zoonoses
PubMed: 36635905
DOI: 10.2174/2772270817666230112123221 -
World Journal of Gastroenterology Jan 2022Viral hepatitis infections are a great burden in children who have received liver transplant. Hepatotropic viruses can cause liver inflammation that can develop into...
Viral hepatitis infections are a great burden in children who have received liver transplant. Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term. Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection, rendering the condition difficult to manage. Prevention strategies using vaccinations are agreeable to patients, safe, cost-effective and practical. Hence, strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant. Although a vaccine has been developed to prevent hepatitis C and E viruses, its use is not licensed worldwide. Consequently, eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy. Good hygiene and sanitation are also important to prevent hepatitis A and E infections. Donor blood products and liver grafts should be screened for hepatitis B, C and E in children who are undergoing liver transplantation. Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E. Moreover, novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.
Topics: Child; Goals; Hepatitis B; Hepatitis C; Hepatitis, Viral, Human; Humans; Liver Transplantation
PubMed: 35110951
DOI: 10.3748/wjg.v28.i3.290 -
Clinical Gastroenterology and... May 2021Etiologies of acute viral hepatitis in high-income countries change with migration of populations, lifestyle changes, and emergence of new pathogens. We analyzed...
BACKGROUND AND AIM
Etiologies of acute viral hepatitis in high-income countries change with migration of populations, lifestyle changes, and emergence of new pathogens. We analyzed etiologies, characteristics, and outcomes of patients with acute viral hepatitis at a tertiary hospital in Spain.
METHODS
We analyzed data from all patients with acute hepatitis (n = 100; 71% male; median age, 42 years; 72% Spanish nationals), older than 16 years, diagnosed in the emergency department of an academic hospital in Barcelona, Spain, from January 2014 through December 2018. Blood samples were collected and patients with serum levels of alanine aminotransferase more than 10-fold the upper limit of normal and markers viral infection were considered to have acute viral hepatitis. We collected clinical information from patients, and samples were analyzed for IgM antibody to hepatitis B (HB) core antigen, HB surface antigen, antibody against hepatitis C virus (HCV), HCV RNA, IgM against hepatitis E virus (HEV), HEV RNA, and IgM against hepatitis A virus (HAV). Patients were followed until resolution of infections or evidence of chronic infection.
RESULTS
The most common etiologies of acute hepatitis were HBV infection (28%), HEV infection (18%), HCV infection (17%), and HAV infection (14%). The main risk factors of the cohort were sexual risk contact and intravenous drug use; 79% of cases of HAV had sexual risk behavior. Twenty-nine percent of patients with acute HAV infection and 29% of patients with HBV infection were immigrants to Spain. Fifty-four patients were hospitalized; jaundice and HCV infection were associated with hospital admission. Three patients died (2 from acute liver failure related to acute HBV infection or HBV and HDV co-infection). Chronic infections developed in 5/28 patients (18%) with acute HBV infection and 7/17 patients (41%) with acute HCV infection.
CONCLUSIONS
Despite universal vaccination against HBV in Spain, HBV remains the most frequent cause of acute viral hepatitis in our emergency department. Almost one-third of cases of acute HBV and HAV infections were immigrants, possibly from countries with suboptimal vaccination programs. A high proportion of patients with acute hepatitis have HEV infection (18%); acute HAV infection was associated with sexual risk behavior.
Topics: Adult; Female; Hepacivirus; Hepatitis A; Hepatitis C; Hepatitis E; Humans; Male; Spain
PubMed: 32663522
DOI: 10.1016/j.cgh.2020.07.006 -
Liver International : Official Journal... Apr 2023Chronic infection with hepatitis B and C viruses (HBV & HCV) is a major contributor to liver disease and liver-related mortality in Uzbekistan. There is a need to...
BACKGROUND & AIMS
Chronic infection with hepatitis B and C viruses (HBV & HCV) is a major contributor to liver disease and liver-related mortality in Uzbekistan. There is a need to demonstrate the feasibility of large-scale simplified testing and treatment to implement a national viral hepatitis elimination program.
METHODS
Thirteen polyclinics were utilized to screen, conduct follow-up biochemical measures and treat chronic HBV and HCV infection in the general adult population. Task shifting and motivational interviewing training allowed nurses to provide rapid screening and general practitioners (GPs) to treat individuals on-site. An electronic medical system tracked individuals through the cascade of care.
RESULTS
The use of rapid tests allowed for screening of 60 769 people for HCV and HBV over 6 months and permitted outdoor testing during the COVID-19 pandemic along with COVID testing. 13%-14% of individuals were lost to follow-up after the rapid test, and another 62%-66% failed to come in for their consultation. One stop testing and treatment did not result in a statistically increase in retention and lack of patient awareness of viral hepatitis was identified as a key factor. Despite training, there were large differences between GPs and patients initiating treatment.
CONCLUSIONS
The current study demonstrated the feasibility of large-scale general population screening and task shifting in low- and middle-income countries. However, such programs need to be proceeded by awareness campaign to minimize loss to follow up. In addition, multiple trainings are needed for GPs to bolster their skills to talk to patients about treatment.
Topics: Adult; Humans; Uzbekistan; COVID-19 Testing; Developing Countries; Pandemics; COVID-19; Hepatitis B; Hepatitis A; Hepatitis C
PubMed: 36606729
DOI: 10.1111/liv.15514 -
Advances in Experimental Medicine and... 2021Interactions between liver cells are closely regulated by Notch signaling. Notch signaling has been reported clinically related to bile duct hypogenesis in Alagille... (Review)
Review
Interactions between liver cells are closely regulated by Notch signaling. Notch signaling has been reported clinically related to bile duct hypogenesis in Alagille syndrome, which is caused by mutations in the Jagged1 gene. Notch activation and hepatocarcinogenesis are closely associated since cancer signaling is affected by the development of liver cells and cancer stem cells. Gene expression and genomic analysis using a microarray revealed that abnormalities in Notch-related genes were associated with the aggressiveness of liver cancer. This pattern was also accompanied with α-fetoprotein- and EpCAM-expressing phenotypes in vitro, in vivo, and in clinical tissues. Hepatitis B or C virus chronic infection or alcohol- or steatosis-related liver fibrosis induces liver cancer. Previous reports demonstrated that HBx, a hepatitis B virus protein, was associated with Jagged1 expression. We found that the Jagged1 and Notch1 signaling pathways were closely associated with the transcription of covalently closed circular hepatitis B virus DNA, which regulated cAMP response element-binding protein, thereby affecting Notch1 regulation by the E3 ubiquitin ligase ITCH. This viral pathogenesis in hepatocytes induces liver cancer. In conclusion, Notch signaling exerts various actions and is a clinical signature associated with hepatocarcinogenesis and liver context-related developmental function.
Topics: Hepatitis; Hepatitis B virus; Humans; Liver Neoplasms; Receptors, Notch; Repressor Proteins; Signal Transduction; Ubiquitin-Protein Ligases
PubMed: 33034027
DOI: 10.1007/978-3-030-55031-8_6