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Scientific Reports Sep 2023This article examines hepatitis B dynamics under distinct infection phases and multiple transmissions. We formulate the epidemic problem based on the characteristics of...
This article examines hepatitis B dynamics under distinct infection phases and multiple transmissions. We formulate the epidemic problem based on the characteristics of the disease. It is shown that the epidemiological model is mathematically and biologically meaningful of its well-posedness (positivity, boundedness, and biologically feasible region). The reproductive number is then calculated to find the equilibria and the stability analysis of the epidemic model is performed. A backward bifurcation is also investigated in the proposed epidemic problem. With the help of two control measures (treatment and vaccination), we develop control strategies to minimize the infected population (acute and chronic). To solve the proposed control problem, we utilize Pontryagin's Maximum Principle. Some simulations are conducted to illustrate the investigation of the analytical work and the effect of control analysis.
Topics: Humans; Hepatitis B, Chronic; Hepatitis B; Epidemics; Epidemiological Models; Reproduction
PubMed: 37696844
DOI: 10.1038/s41598-023-39582-9 -
International Journal of Molecular... Dec 2023Hepatitis is an inflammatory liver disease primarily caused by hepatitis A (HAV), B (HBV), C (HCV), D (HDV), and E (HEV) viruses. The chronic forms of hepatitis... (Review)
Review
Hepatitis is an inflammatory liver disease primarily caused by hepatitis A (HAV), B (HBV), C (HCV), D (HDV), and E (HEV) viruses. The chronic forms of hepatitis resulting from HBV and HCV infections can progress to cirrhosis or hepatocellular carcinoma (HCC), while acute hepatitis can lead to acute liver failure, sometimes resulting in fatality. Viral hepatitis was responsible for over 1 million reported deaths annually. The treatment of hepatitis caused by viral infections currently involves the use of interferon-α (IFN-α), nucleoside inhibitors, and reverse transcriptase inhibitors (for HBV). However, these methods do not always lead to a complete cure for viral infections, and chronic forms of the disease pose significant treatment challenges. These facts underscore the urgent need to explore novel drug developments for the treatment of viral hepatitis. The discovery of the CRISPR/Cas9 system and the subsequent development of various modifications of this system have represented a groundbreaking advance in the quest for innovative strategies in the treatment of viral infections. This technology enables the targeted disruption of specific regions of the genome of infectious agents or the direct manipulation of cellular factors involved in viral replication by introducing a double-strand DNA break, which is targeted by guide RNA (spacer). This review provides a comprehensive summary of our current knowledge regarding the application of the CRISPR/Cas system in the regulation of viral infections caused by HAV, HBV, and HCV. It also highlights new strategies for drug development aimed at addressing both acute and chronic forms of viral hepatitis.
Topics: Humans; CRISPR-Cas Systems; Carcinoma, Hepatocellular; Liver Neoplasms; RNA, Guide, CRISPR-Cas Systems; Hepatitis Viruses; Hepatitis A; Hepatitis C; Antiviral Agents
PubMed: 38203503
DOI: 10.3390/ijms25010334 -
Communicable Diseases Intelligence... Aug 2023For 30 years the Australian Paediatric Surveillance Unit (APSU) has conducted national surveillance of rare communicable diseases and rare complications of communicable...
For 30 years the Australian Paediatric Surveillance Unit (APSU) has conducted national surveillance of rare communicable diseases and rare complications of communicable diseases. In this report, we describe the results of thirteen such studies surveyed by the APSU in 2022, including reported case numbers and incidence estimates, demographics, clinical features, management and short-term outcomes. Conditions described are: acute flaccid paralysis (AFP); congenital cytomegalovirus (cCMV); neonatal and infant herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV) and paediatric HIV infection; severe complications of influenza; juvenile-onset recurrent respiratory papillomatosis (JoRRP); congenital rubella infection/syndrome; congenital varicella syndrome (CVS) and neonatal varicella infection (NVI); and the new conditions dengue; Q fever; and severe acute hepatitis. In 2022, cases of severe complications of influenza were reported to the APSU for the first time since 2019. This likely reflects the easing of government-mandated restrictions imposed in 2020-2021 to curb the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the re-emergence of a range of infectious diseases. As previously, AFP surveillance by the APSU contributed to Australia achieving a minimum target incidence of one AFP case per 105 children aged less than 15 years. Cases of JoRRP and NVI were reported in 2022. This indicates potential gaps in human papillomavirus (HPV) and varicella vaccination coverage respectively, especially in high-risk groups such as young migrant and refugee women of childbearing age from countries without universal vaccination programs. Paediatric HIV case numbers resulting from mother-to-child-transmission (MTCT) of HIV remain low in Australia due to use of effective intervention strategies. However, there has been an increase in the number of imported cases of HIV in children (mainly perinatally-acquired) from countries with a high HIV prevalence. Without effective vaccines, there has been no decline in the incidence of congenital CMV and neonatal HSV, indicating the importance of early identification and management to reduce morbidity and mortality. The first cases of dengue, Q fever and severe acute hepatitis were received by APSU in 2022, including two cases of acute hepatitis in which aetiology has not been confirmed to date. The APSU has an important ongoing role in monitoring rare childhood infections.
Topics: Infant; Infant, Newborn; Pregnancy; Humans; Female; Child; HIV Infections; Chickenpox; Influenza, Human; Q Fever; alpha-Fetoproteins; Australia; Infectious Disease Transmission, Vertical; Communicable Diseases; Cytomegalovirus Infections; Rubella Syndrome, Congenital; Hepatitis; Dengue
PubMed: 37817313
DOI: 10.33321/cdi.2023.47.46 -
Science Translational Medicine Jul 2023Severe acute hepatitis of unknown etiology in children is under investigation in 35 countries. Although several potential etiologic agents have been investigated, a...
Severe acute hepatitis of unknown etiology in children is under investigation in 35 countries. Although several potential etiologic agents have been investigated, a clear cause for the liver damage observed in these cases remains to be identified. Using VirScan, a high-throughput antibody profiling technology, we probed the antibody repertoires of nine cases of severe acute hepatitis of unknown etiology treated at Children's of Alabama and compared their antibody responses with 38 pediatric and 470 adult controls. We report increased adeno-associated dependoparvovirus A (AAV-A) breadth in cases relative to controls and adeno-associated virus 2 (AAV-2) peptide responses that were conserved in seven of nine cases but rarely observed in pediatric and adult controls. These findings suggest that AAV-2 is a likely etiologic agent of severe acute hepatitis of unknown etiology.
Topics: Adult; Humans; Child; Dependovirus; Hepatitis; Liver Diseases
PubMed: 37494473
DOI: 10.1126/scitranslmed.adh9917 -
Microorganisms Dec 2023The hepatitis E virus (HEV) is a widespread human infection that causes mainly acute infection and can evolve to a chronic manifestation in immunocompromised... (Review)
Review
The hepatitis E virus (HEV) is a widespread human infection that causes mainly acute infection and can evolve to a chronic manifestation in immunocompromised individuals. In addition to the common strains of hepatitis E virus (HEV-A), known as , pathogenic to humans, a genetically highly divergent rat origin hepevirus (RHEV) can cause hepatitis possessing a potential risk of cross-species infection and zoonotic transmission. , formerly known as C, is a single-stranded RNA virus, recently reassigned to genus in the family, including genotypes C1 and C2. RHEV primarily infects rats but has been identified as a rodent zoonotic virus capable of infecting humans through the consumption of contaminated food or water, causing both acute and chronic hepatitis cases in both animals and humans. This review compiles data concluding that 60% (295/489) of RHEV infections are found in Asia, being the continent with the highest zoonotic and transmission potential. Asia not only has the most animal cases but also 16 out of 21 human infections worldwide. Europe follows with 26% (128/489) of RHEV infections in animals, resulting in four human cases out of twenty-one globally. Phylogenetic analysis and genomic sequencing will be employed to gather global data, determine epidemiology, and assess geographical distribution. This information will enhance diagnostic accuracy, pathogenesis understanding, and help prevent cross-species transmission, particularly to humans.
PubMed: 38138140
DOI: 10.3390/microorganisms11122996 -
Hepatology International Jun 2024Children and adolescents are at high risk for acute viral hepatitis (AVH), but epidemiological research focusing on them has been overshadowed by adult chronic B and C....
BACKGROUND
Children and adolescents are at high risk for acute viral hepatitis (AVH), but epidemiological research focusing on them has been overshadowed by adult chronic B and C. We provide global, regional, and national estimates of the AVH burden and their trends on people under 20 years from 1990 to 2019.
METHODS
AVH data from Global Burden of Disease Study (GBD) 2019 was used. Incidence and disability-adjusted life years (DALYs) were calculated, analyzing trends with estimated annual percentage change (EAPC) and Joinpoint regression.
RESULTS
In 2019, 156.39 (95% uncertainty interval 145.20-167.16) million new cases of AVH were reported among children and adolescents globally, resulting in 1.98 (1.50-2.55) million DALYs. Incidence rates for young children (< 5 years), older children (5-9 years), and adolescents (10-19 years) were 12,799 (11,068-14,513), 5,108 (4829-5411), and 3020 (2724-3339) per 100,000 population, respectively. The global AVH incidence displayed a linear decline with an EAPC of - 0.66 (- 0.68 to - 0.65). High-incidence regions included sub-Saharan Africa, Oceania, South Asia, and Central Asia, with India, Pakistan, and Nigeria facing the greatest burden. Leading causes were hepatitis A, followed by hepatitis E, B, and C. All hepatitis types showed declining trends, especially hepatitis B. Furthermore, we confirmed the association between the AVH incidence and the socioeconomics, vaccine, and advanced liver diseases.
CONCLUSION
Effective vaccines and treatments for hepatitis B and C offer eradication opportunities. Broadening diagnostic and therapeutic coverage is vital to address disparities in service provision for children and adolescents.
Topics: Humans; Adolescent; Child; Global Burden of Disease; Hepatitis, Viral, Human; Child, Preschool; Incidence; Female; Male; Acute Disease; Disability-Adjusted Life Years; Global Health; Infant; Young Adult
PubMed: 38528292
DOI: 10.1007/s12072-024-10640-2 -
The Journal of Infection Jan 2024The sudden outbreak of severe acute hepatitis of unknown aetiology (SAHUA) in the first half of 2022 affected more than 1010 children in 35 countries worldwide. Dire... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The sudden outbreak of severe acute hepatitis of unknown aetiology (SAHUA) in the first half of 2022 affected more than 1010 children in 35 countries worldwide. Dire clinical outcomes, such as acute liver failure necessitating transplantation, neurological symptoms, long-term sequelae, and death, highlight the need to determine the pathogenesis of this condition. Hypotheses on the aetiology include adenovirus and SARS-CoV-2 infections and an aberrant immune response to multiple pathogen exposure following lifting of lockdown measures but further investigation is required to reach an informed consensus.
METHODS
A literature search was performed on MEDLINE and EMBASE in accordance with PRISMA guidelines for systematic reviews. Primary studies reporting data on severe acute hepatitis of unknown aetiology in children from the COVID-19 era were selected for inclusion in our review. Data on patient demographics, clinical presentation and outcomes, and diagnostic testing for coinfection were extracted. Meta-analysis used a random-effects model.
RESULTS
The 33 included studies (30 case series and 3 case-control studies) described a total of 3636 cases of SAHUA (reported 1 January, 2019-31 December, 2022), with a median age of 3.5 years. Of these, 214 children (5.9%) received a liver transplant and 66 (1.8%) died. Whilst data on diagnostic testing was incomplete, the most frequently detected coinfections were with adenovirus and/or adeno-associated virus 2 (AAV2). Other common childhood respiratory and enteric pathogens, such as enterovirus, rhinovirus, and herpesviruses (EBV and HHV-6), were also identified.
CONCLUSION
Coinfection with AAV2 and other common childhood pathogens may predispose children to develop this novel severe hepatitis. Altered susceptibility and response to such pathogens may be a consequence of immunological naivety following pandemic restrictions. Further investigations are needed to generate high-quality evidence on aetiology for different patient demographics and geographical areas.
Topics: Child; Humans; Child, Preschool; Coinfection; COVID-19; Disease Outbreaks; Pandemics; Hepatitis; Acute Disease
PubMed: 38007049
DOI: 10.1016/j.jinf.2023.11.011 -
Microbiology Spectrum Dec 2023Hepatitis E virus (HEV) infection constitutes a significant health problem worldwide. In recent years, in addition to the zoonotic HEV3 and HEV4, emerging highly...
Hepatitis E virus (HEV) infection constitutes a significant health problem worldwide. In recent years, in addition to the zoonotic HEV3 and HEV4, emerging highly divergent hepevirus of rat origin (rat HEV [RHEV]) has been associated with human acute and chronic hepatitis. As environmental surveillance can be a complementary tool to explore emerging viruses of human and rodent origin, we investigated the epidemiology and the genetic variability of RHEV targeting 14 wastewater treatment plants in an Italian geographic area considered a hot spot for HEV infection in humans. Our results revealed that RHEV is a significant component of the wastewater microbiota with viral RNA detected in 43.9% of the specimens tested, adding further evidence to the need to investigate more in depth the real burden of RHEV infections in humans.
Topics: Animals; Humans; Rats; Hepatitis E; Wastewater; Phylogeny; Genotype; Hepatitis E virus; Italy
PubMed: 37850788
DOI: 10.1128/spectrum.02675-23 -
Viruses Aug 2023The story of the discovery of hepatitis E originated in the late 1970s with my extreme belief that there was a hidden saga in the relationship between jaundice and... (Review)
Review
The story of the discovery of hepatitis E originated in the late 1970s with my extreme belief that there was a hidden saga in the relationship between jaundice and pregnancy in developing countries and the opportunity for a massive epidemic of viral hepatitis, which hit the Gulmarg Kashmir region in November 1978. Based on data collected from a door-to-door survey, the existence of a new disease, epidemic non-A, non-B hepatitis, caused by a hitherto unknown hepatitis virus, was announced. This news was received by the world community with hype and skepticism. In the early 1980s, the world watched in awe as an extreme example of human self-experimentation led to the identification of VLP. In 1990, a cDNA clone from the virus responsible for epidemic non-A, non-B hepatitis was isolated. Over the years, we traversed three eras of ambiguity, hope, and hype of hepatitis E research and conducted several seminal studies to understand the biology of HEV and manifestations of hepatitis E. Many milestones have been reached on the long and winding road of hepatitis E research to understand the structure, biology, and diversity of the agent, changing the behavior of the pathogen in developed countries, and the discovery of a highly effective vaccine.
Topics: Female; Pregnancy; Humans; Hepatitis E; Global Health; Hepatitis C; DNA, Complementary; Epidemics
PubMed: 37632090
DOI: 10.3390/v15081745 -
The Turkish Journal of Gastroenterology... Nov 2023Autoimmune hepatitis (AIH) is a rare, immune-mediated liver disease. It has a heterogeneous nature with varied clinical presentations. The management of patients with...
Diagnosis and Treatment of Autoimmune Hepatitis: Questions, Answers, and Illustrative Cases: Endorsed by Autoimmune Liver Diseases Special Interest Group, Turkish Association for the Study of Liver.
Autoimmune hepatitis (AIH) is a rare, immune-mediated liver disease. It has a heterogeneous nature with varied clinical presentations. The management of patients with AIH is challenging in many ways. The main difficulties are inexperience due to the rarity of the disease, diagnostic confusion in controversial areas such as variant/overlap cases, acute presentations, the presence of non-alcoholic fatty liver disease or drug-induced liver injury features, and the long and complex course of treatment. Here, we provide a clear, concise, and visualized review regarding the diagnosis and treatment of AIH, including illustrative cases.
Topics: Humans; Hepatitis, Autoimmune; Public Opinion; Liver Diseases; Chemical and Drug Induced Liver Injury
PubMed: 37947207
DOI: 10.5152/tjg.2023.23242