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PLoS Pathogens Oct 2023Immune correlates of hepatitis C virus (HCV) clearance and control remain poorly defined due to the lack of an informative animal model. We recently described acute and...
Immune correlates of hepatitis C virus (HCV) clearance and control remain poorly defined due to the lack of an informative animal model. We recently described acute and chronic rodent HCV-like virus (RHV) infections in lab mice. Here, we developed MHC class I and class II tetramers to characterize the serial changes in RHV-specific CD8 and CD4 T cells during acute and chronic infection in C57BL/6J mice. RHV infection induced rapid expansion of T cells targeting viral structural and nonstructural proteins. After virus clearance, the virus-specific T cells transitioned from effectors to long-lived liver-resident memory T cells (TRM). The effector and memory CD8 and CD4 T cells primarily produced Th1 cytokines, IFN-γ, TNF-α, and IL-2, upon ex vivo antigen stimulation, and their phenotype and transcriptome differed significantly between the liver and spleen. Rapid clearance of RHV reinfection coincided with the proliferation of virus-specific CD8 TRM cells in the liver. Chronic RHV infection was associated with the exhaustion of CD8 T cells (Tex) and the development of severe liver diseases. Interestingly, the virus-specific CD8 Tex cells continued proliferation in the liver despite the persistent high-titer viremia and retained partial antiviral functions, as evident from their ability to degranulate and produce IFN-γ upon ex vivo antigen stimulation. Thus, RHV infection in mice provides a unique model to study the function and fate of liver-resident T cells during acute and chronic hepatotropic infection.
Topics: Mice; Animals; Hepacivirus; Persistent Infection; Mice, Inbred C57BL; CD8-Positive T-Lymphocytes; Hepatitis C; Hepatitis C, Chronic; Phenotype
PubMed: 37812637
DOI: 10.1371/journal.ppat.1011697 -
World Journal of Gastroenterology Jan 2021Human hepatitis viruses (HHVs) include hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus, and hepatitis E virus and can cause... (Review)
Review
Human hepatitis viruses (HHVs) include hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus, and hepatitis E virus and can cause liver inflammation in their common human host. Usually, HHV is rapidly cleared by the immune system, following acute HHV invasion. The morbidities associated with hepatitis A virus and hepatitis E virus infection occur shortly after their intrusion, in the acute stage. Nevertheless, the viral infectious process can persist for a long period of time, especially in HBV and HCV infection, leading to chronic hepatitis and further progressing to hepatic cirrhosis and liver cancer. HHV infection brings about complications in other organs, and both acute and chronic hepatitis have been associated with clinical presentations outside the liver. Vascular involvement with cutaneous and systemic vasculitis is a well-known extrahepatic presentation; moreover, there is growing evidence for a possible causal relationship between viral pathogens and vasculitis. Except for hepatitis delta virus, other HHVs have participated in the etiopathogenesis of cutaneous and systemic vasculitis different mechanisms, including direct viral invasion of vascular endothelial cells, immune complex-mediated vessel wall damage, and autoimmune responses with stimulation of autoreactive B-cells and impaired regulatory T-cells. Cryoglobulinemic vasculitis and polyarteritis nodosa are recognized for their association with chronic HHV infection. Although therapeutic guidelines for HHV-associated vasculitis have not yet been established, antiviral therapy should be initiated in HBV and HCV-related systemic vasculitis in addition to the use of corticosteroids. Plasma exchange and/or combined cyclophosphamide and corticosteroid therapy can be considered in patients with severe life-threatening vasculitis manifestations.
Topics: Cryoglobulinemia; Endothelial Cells; Hepacivirus; Hepatitis B virus; Hepatitis C; Humans
PubMed: 33505148
DOI: 10.3748/wjg.v27.i1.19 -
Viruses Jul 2019Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. HEV is... (Review)
Review
Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. HEV is largely circulating in the west and is associated with several hepatic and extrahepatic diseases. HEV Genotype 1 and 2 infections are waterborne and causative for epidemics in the tropics, while genotype 3 and 4 infections are zoonotic diseases and are mainly transmitted by ingestion of undercooked pork in industrialized nations. The clinical course of these infections differs: genotype 1 and 2 infection can cause acute illness and can lead to acute liver failure (ALF) or acute on chronic liver failure (ACLF) with a high mortality rate of 20% in pregnant women. In contrast, the majority of HEV GT-3 and -4 infections have a clinically asymptomatic course and only rarely lead to acute on chronic liver failure in elderly or patients with underlying liver disease. Immunosuppressed individuals infected with genotype 3 or 4 may develop chronic hepatitis E, which then can lead to life-threatening cirrhosis. Furthermore, several extra-hepatic manifestations affecting various organs have been associated with ongoing or previous HEV infections but the causal link for many of them still needs to be proven. There is no approved specific therapy for the treatment of acute or chronic HEV GT-3 or -4 infections but off-label use of ribavirin has been demonstrated to be safe and effective in the majority of patients. However, in approximately 15% of chronically HEV infected patients, cure is not possible.
Topics: Animals; Antiviral Agents; Chronic Disease; Female; Genotype; Hepatitis E; Hepatitis E virus; Humans; Immunocompromised Host; Pregnancy; Pregnancy Complications, Infectious; Ribavirin
PubMed: 31284447
DOI: 10.3390/v11070617 -
Gaceta Medica de Mexico 2022At the beginning of 2022, in the United Kingdom, and later in several European countries, a group of pediatric patients who developed acute hepatitis of so far unknown...
At the beginning of 2022, in the United Kingdom, and later in several European countries, a group of pediatric patients who developed acute hepatitis of so far unknown origin was reported. Clinical data include nausea, vomiting, jaundice, and liver failure; some patients require liver transplantation. The affected population is younger than 10 years of age. The probable etiological agent is adenovirus genotype F41, and toxic factors have been ruled out, as well as a relationship with COVID-19. There are several theories to explain this phenomenon, which are being investigated.
Topics: Humans; Child; COVID-19; Hepatitis; Jaundice; Liver Transplantation; Acute Disease
PubMed: 36572034
DOI: 10.24875/GMM.M22000703 -
World Journal of Gastroenterology Dec 2021Viral hepatitis can result in important morbidity and mortality, with its impact on health conditioned by the specific type of hepatitis, the geographical region of... (Review)
Review
Viral hepatitis can result in important morbidity and mortality, with its impact on health conditioned by the specific type of hepatitis, the geographical region of presentation and the development and access to new drugs, among other factors. Most acute presentation forms are self-limiting and may even go unnoticed, with just a small percentage of cases leading to acute liver failure that may necessitate transplantation or even cause the death of the patient. However, when they become chronic, as in the case of hepatitis B virus and C virus, unless they are diagnosed and treated adequately they may have severe consequences, like cirrhosis or hepatocarcinoma. Understanding of the mechanisms of transmission, the pathogenesis, the presence of vaccinations and the development over recent years of new highly-efficient, potent drugs have meant that we are now faced with a new scenario in the management of viral hepatitis, particularly hepatitis B virus and hepatitis C virus. The spectacular advances in hepatitis C virus treatment have led the World Health Organization to propose the objective of its eradication by 2030. The key aspect to achieving this goal is to ensure that these treatments reach all the more vulnerable population groups, in whom the different types of viral hepatitis have a high prevalence and constitute a niche that may perpetuate infection and hinder its eradication. Accordingly, micro-elimination programs assume special relevance at the present time.
Topics: Antiviral Agents; Carcinoma, Hepatocellular; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Hepatitis, Viral, Human; Humans; Liver Neoplasms
PubMed: 35068856
DOI: 10.3748/wjg.v27.i47.8081 -
Viruses Jul 2023Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water... (Review)
Review
Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development.
Topics: Animals; Humans; Female; Swine; Pregnancy; Rabbits; Rats; Sheep; Hepatitis E virus; Hepatitis E; Europe; Viral Vaccines; Persistent Infection; Vaccines, Synthetic; Zoonoses
PubMed: 37515244
DOI: 10.3390/v15071558 -
The Korean Journal of Gastroenterology... Feb 2023Autoimmune liver disease is an important immune-mediated pathologic entity involving the liver and intrahepatic bile duct, including autoimmune hepatitis, primary... (Review)
Review
Autoimmune liver disease is an important immune-mediated pathologic entity involving the liver and intrahepatic bile duct, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Although it is necessary to ascertain its presence in acute or chronic liver disease without common causes, it is not easy to diagnose this disease straightforwardly because of its rarity. Recently, the incidence and prevalence of autoimmune hepatitis and primary biliary cholangitis have increased in several regions. In contrast, there is limited data dealing with the trend of the epidemiology of primary sclerosing cholangitis worldwide. Physicians should consider the epidemiologic characteristics of autoimmune liver disease because early diagnosis and proper treatment might prevent the progression of advanced liver disease. In addition, more sophisticated epidemiologic studies will be needed to elucidate the trend of these rare diseases nationwide.
Topics: Humans; Hepatitis, Autoimmune; Liver Cirrhosis, Biliary; Cholangitis, Sclerosing; Autoimmune Diseases; Liver Diseases; Liver
PubMed: 36824033
DOI: 10.4166/kjg.2023.007 -
Hepatology International Sep 2020Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and progressive inflammatory liver injury in patients with a history of prolonged periods of... (Review)
Review
Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and progressive inflammatory liver injury in patients with a history of prolonged periods of excess alcohol consumption and recent heavy alcohol abuse. Severe AH is a life-threatening form of alcohol-associated liver disease with a high short-term mortality rate around 30-50% at one month from the initial presentation. A large number of pro-inflammatory mediators, metabolic pathways, transcriptional factors and epigenetic factors have been suggested to be associated with the development and progression of AH. Several factors may contribute to liver failure and mortality in patients with severe AH including hepatocyte death, inflammation, and impaired liver regeneration. Although the pathogeneses of AH have been extensively investigated and many therapeutic targets have been identified over the last five decades, no new drugs for AH have been successfully developed. In this review, we discuss interleukin-22 (IL-22) biology and its roles of anti-apoptosis, anti-fibrosis, anti-oxidation, anti-bacterial infection and regenerative stimulation in protecting against liver injury in many preclinical models including several recently developed models such as chronic-plus-binge ethanol feeding, acute-on-chronic liver failure, C-X-C motif chemokine ligand 1 plus high-fat diet-induced nonalcoholic steatohepatitis. Finally, clinical trials of IL-22 for the treatment of AH are also discussed, which showed some promising benefits for AH patients.
Topics: Hepatitis, Alcoholic; Humans; Interleukins; Liver; Liver Regeneration; Models, Biological; Interleukin-22
PubMed: 32892258
DOI: 10.1007/s12072-020-10082-6 -
Bulletin of the World Health... Sep 2022Investigation of an outbreak of acute hepatitis of unknown cause in children may prompt research into other unexplained cases. Vijay Shankar Balakrishnan reports.
Investigation of an outbreak of acute hepatitis of unknown cause in children may prompt research into other unexplained cases. Vijay Shankar Balakrishnan reports.
Topics: Child; Disease Outbreaks; Hepatitis; Humans
PubMed: 36062241
DOI: 10.2471/BLT.22.020922 -
Food and Environmental Virology Sep 2023One of the most frequent causes of acute viral hepatitis is hepatitis E virus (HEV) causing 20 million infections worldwide each year and 44,000 deaths. Studies on HEV... (Review)
Review
One of the most frequent causes of acute viral hepatitis is hepatitis E virus (HEV) causing 20 million infections worldwide each year and 44,000 deaths. Studies on HEV in the Iberian Peninsula have been increasing through time with HEV infection being identified in humans and animals. The aim of the present systematic review was to compile and evaluate all the published data on HEV from studies performed in humans, animals and environmental samples in the Iberian Peninsula. The electronic databases Mendeley, PubMed, Scopus, and Web of Science were thoroughly searched, and research published up until February 01, 2023 were included. Resulting in a total of 151 eligible papers by full reading and application of PRISMA exclusion/inclusion criteria. Overall, the present review shows that several HEV genotypes, namely HEV-1, 3, 4, and 6 as well as Rocahepevirus, are circulating in humans, animals, and in the environment in the Iberian Peninsula. HEV-3 was the most common genotype circulating in humans in Portugal and Spain, as expected for developed countries, with HEV-1 only being detected in travelers and emigrants from HEV endemic regions. Spain is the biggest pork producer in Europe and given the high circulation of HEV in pigs, with HEV-3 being primarily associated to zoonotic transmission through consumption of swine meat and meat products, in our opinion, the introduction of an HEV surveillance system in swine and inclusion of HEV in diagnostic routines for acute and chronic human hepatitis would be important. Additionally, we propose that establishing a monitoring mechanism for HEV is crucial in order to gain a comprehensive understanding of the prevalence of this illness and the various strains present in the Iberian Peninsula, as well as their potential impact on public health.
Topics: Humans; Animals; Swine; Hepatitis E virus; Hepatitis E; Europe; Public Health; Meat; Genotype; Swine Diseases; Phylogeny
PubMed: 37434079
DOI: 10.1007/s12560-023-09560-5