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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 -
European Journal of Gastroenterology &... Dec 2021Patients with acute hepatitis A virus (HAV) infection are at risk of developing acute kidney injury (AKI) which may result in increased healthcare resource utilization...
BACKGROUND
Patients with acute hepatitis A virus (HAV) infection are at risk of developing acute kidney injury (AKI) which may result in increased healthcare resource utilization and worse clinical outcomes. We investigated the impact of AKI on healthcare utilization and clinical outcomes in patients hospitalized with acute HAV infection utilizing a large database.
METHODS
We queried the National Inpatient Sample (NIS) 2007-2014 to identify acute HAV infection-related hospitalizations with and without AKI. Primary outcomes were prevalence of AKI and its predictors with secondary outcomes included the mean length of stay (LOS), hospitalization cost and mortality in both groups.
RESULTS
Out of 68 364 acute HAV infection-related hospitalizations, 47 620 met our study criteria and 7458 (15.7%) had concurrent AKI. HAV patients with AKI were older (62.5 vs. 53.7 years; P value <0.001). A higher mean LOS (10.03 vs. 5.6 days; P value <0.001) and mean total hospitalization cost ($27 171.35 vs. $12 790.26; P value <0.001) were observed in HAV patients with the AKI group. A total of 1032 patients (13.8%) in the AKI group died during the same hospitalization as compared to 681 patients (1.5%) in the non-AKI group, P value <0.001. AKI in HAV was also found to be an independent predictor of mortality [adjusted odds ratio (aOR), 3.28; 95% confidence interval, 2.23-4.84; P value <0.001) after adjusting for the confounding factors.
CONCLUSION
We found that 15.67% of patients hospitalized with acute HAV had AKI which contributed to increased healthcare utilization and higher mortality which is preventable.
Topics: Acute Kidney Injury; Hepatitis A; Hepatitis A virus; Hospital Mortality; Hospitalization; Humans; Length of Stay; Patient Acceptance of Health Care; Retrospective Studies; Risk Factors
PubMed: 34138764
DOI: 10.1097/MEG.0000000000002230 -
Virology Journal May 2011Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but...
BACKGROUND
Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but rarely fulminant. There is growing concern about change in pattern from asymptomatic childhood infection to an increased incidence of symptomatic disease in the adult population.
OBJECTIVE
In-depth analysis of immunological, viral quantification and genotype of acute and fulminant hepatitis A virus.
METHODS
Serum samples obtained from 1009 cases of suspected acute viral hepatitis was employed for different biochemical and serological examination. RNA was extracted from blood serum, reverse transcribed into cDNA and amplified using nested PCR for viral quantification, sequencing and genotyping. Immunological cell count from freshly collected whole blood was carried out by fluorescence activated cell sorter.
RESULTS
Fulminant hepatitis A was mostly detected with other hepatic viruses. CD8+ T cells count increases in fulminant hepatitis to a significantly high level (P = 0.005) compared to normal healthy control. The immunological helper/suppressor (CD4+/CD8+) ratio of fulminant hepatitis was significantly lower compared to acute cases. The serologically positive patients were confirmed by RT-PCR and total of 72 (69.2%) were quantified and sequenced. The average quantitative viral load of fulminant cases was significantly higher (P < 0.05). There was similar genotypic distribution in both acute and fulminant category, with predominance of genotype IIIA (70%) compared to IA (30%).
CONCLUSIONS
Immunological factors in combination with viral load defines the severity of the fulminant hepatitis A. Phylogenetic analysis of acute and fulminant hepatitis A confirmed genotypes IIIA as predominant against IA with no preference of disease severity.
Topics: Adolescent; Adult; CD4-CD8 Ratio; CD8-Positive T-Lymphocytes; Child; Child, Preschool; Cluster Analysis; Female; Genotype; Hepatitis A; Hepatitis A virus; Humans; India; Male; Middle Aged; Molecular Epidemiology; Phylogeny; RNA, Viral; Sequence Analysis, DNA; Severity of Illness Index; Viral Load; Young Adult
PubMed: 21605420
DOI: 10.1186/1743-422X-8-254 -
Annals of Agricultural and... Sep 2020Hepatitis A Virus (HAV), reportedly the most common cause of acute viral hepatitis in developing countries, infects millions of people worldwide each year. The aim of...
INTRODUCTION AND OBJECTIVE
Hepatitis A Virus (HAV), reportedly the most common cause of acute viral hepatitis in developing countries, infects millions of people worldwide each year. The aim of the study is to investigate the seropositivity of anti-hepatitis A virus (HAV) IgG and IgM in all age groups in Erzurum, and to determine the effect of various factors such as age, gender, climatic conditions and HAV vaccination (included in 2012 in the National Immunization Schedule on seroprevalence) on the seropositivity.
MATERIAL AND METHODS
The serological results of 25,007 individuals referred to Erzurum Public Health Microbiology Laboratory between January 2015 - December 2018 were retrospectively reviewed to test for the presence of anti-HAV IgG and IgM. The patient ages were 0-93 years. Serum samples were analyzed by ELISA. S/CO values of ≥1.00 and >1.21 were considered positive for anti-HAV IgG and IgM, respectively; results below this value were considered negative.
RESULTS
Anti-HAV IgG and IgM seropositivities were 87.3% and 0.2%, respectively. Anti-HAV IgG prevalence - 88.5% and 86.4%, anti-HAV IgM positivity - 0.1% and 0.3% in men and women. Anti-HAV IgG seroprevalence - 87%, 73.2%, 58.7%, 75.2%, 86.1%, 89.8%, 96.1%, 99.1%, 99.1% and 99.3%, respectively, at 0-4, 5-9 10-14, 15-19, 20-24, 25-29, 30-39, 40-49, 50-59 and >60 age groups. Anti-HAV IgM seropositivity - 0, 0.1%, 0.7%, 0.7%, 0.3%, 0, 0.1%, 0.2%, 0.1%, and 0.2%, respectively, in the same age groups. Anti-HAV IgM positivity was the highest in November - 36(0.97%.
CONCLUSIONS
In Erzurum, anti-HAV IgG prevalence is tremendously high, whereas prevalence of anti-HAV IgM is exceptionally low, especially in the paediatric age group. Therefore, HAV vaccine is provided free of charge in Turkey, including Erzurum, since 2012.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Hepatitis A; Hepatitis A Antibodies; Hepatitis A virus; Humans; Infant; Infant, Newborn; Male; Middle Aged; Prevalence; Retrospective Studies; Seroepidemiologic Studies; Turkey; Young Adult
PubMed: 32955233
DOI: 10.26444/aaem/125394 -
Annals of Hepatology 2012Hepatitis A is the most common type of viral hepatitis in Mexico. The change of hepatitis A epidemiology in Mexico from high to intermediate endemicity leads to...
BACKGROUND
Hepatitis A is the most common type of viral hepatitis in Mexico. The change of hepatitis A epidemiology in Mexico from high to intermediate endemicity leads to increasing susceptible adults for severe illness.
OBJECTIVE
To describe the clinical characteristics and hospital outcome of adult patients with acute hepatitis A infection, and determine risk factor for mortality.
MATERIAL AND METHODS
This is a retrospective observational, multicentre study in Mexico City and in Guatemala City. All inhospital patients were followed until discharge or death. Risk factors for death/acute liver failure were identified.
RESULTS
Forty seven patients were analyzed, sixty percent were male, the prodrome phase was from 3 to 30 days. The three most common symptoms were fever, malaise and jaundice, with 87%, 74% and 62% respectively. The incidence of patients who were treated with antibiotics before hospital admission was up to 34%. Unnecessary imaging studies and out of guidelines drugs were used. Presence of encephalopathy, leukocytes > 19,000/mL, blood urea nitrogen > 36 mg/dL, creatinine > 2 mg/dL, albumin < 2.5 mg/dL and total bilirubin > 9.6 mg/dL, are predictors of mortality. Serum creatinine > 2 mg/dL has the best sensibility and specificity for predicting fulminant hepatitis/death.
CONCLUSION
Acute hepatitis A infection in adults is associated some unnecessary diagnostic and therapeutic approach. Could be associated with fulminant hepatitis, and a creatinine value > 2 mg/dL is the best predictor for fulminant hepatitis and death.
Topics: Acute Disease; Adult; Anti-Bacterial Agents; Antiviral Agents; Biomarkers; Disease Progression; Female; Guatemala; Hepatitis A; Humans; Liver Failure, Acute; Male; Mexico; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Unnecessary Procedures; Young Adult
PubMed: 22947525
DOI: No ID Found -
Medicinal Research Reviews Sep 2014Hepatitis A virus (HAV) is a faeco-orally transmitted picornavirus and is one of the main causes of acute hepatitis worldwide. An overview of the molecular biology of... (Review)
Review
Hepatitis A virus (HAV) is a faeco-orally transmitted picornavirus and is one of the main causes of acute hepatitis worldwide. An overview of the molecular biology of HAV is presented with an emphasis on recent findings. Immune evasion strategies and a possible correlation between HAV and atopy are discussed as well. Despite the availability of efficient vaccines, antiviral drugs targeting HAV are required to treat severe cases of fulminant hepatitis, contain outbreaks, and halt the potential spread of vaccine-escape variants. Additionally, such drugs could be used to shorten the period of illness and decrease associated economical costs. Several known inhibitors of HAV with various mechanisms of action will be discussed. Since none of these molecules is readily useable in the clinic and since the availability of an anti-HAV drug would be of clinical importance, increased efforts should be targeted toward discovery and development of such antivirals.
Topics: Antiviral Agents; Cells, Cultured; Genome, Viral; Hepatitis A; Hepatitis A virus; Humans; Immune Evasion; Protein Biosynthesis; T-Lymphocytes, Cytotoxic; Virus Replication
PubMed: 23722879
DOI: 10.1002/med.21292 -
Cold Spring Harbor Perspectives in... Apr 2019There are many similarities in the epidemiology and transmission of hepatitis A virus (HAV) and hepatitis E virus (HEV) genotype (gt)3 infections in the United States.... (Review)
Review
There are many similarities in the epidemiology and transmission of hepatitis A virus (HAV) and hepatitis E virus (HEV) genotype (gt)3 infections in the United States. Both viruses are enterically transmitted, although specific routes of transmission are more clearly established for HAV than for HEV: HAV is restricted to humans and primarily spread through the fecal-oral route, while HEV is zoonotic with poorly understood modes of transmission in the United States. New cases of HAV infection have decreased dramatically in the United States since infant vaccination was recommended in 1996. In recent years, however, outbreaks have occurred among an increasingly susceptible adult population. Although HEV is the most common cause of acute viral hepatitis in developing countries, it is rarely diagnosed in the United States.
Topics: Animals; Hepatitis A; Hepatitis A virus; Hepatitis E; Hepatitis E virus; Humans; United States; Viral Hepatitis Vaccines; Zoonoses
PubMed: 29712684
DOI: 10.1101/cshperspect.a033431 -
Clinical and Molecular Hepatology Jun 2017Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types...
BACKGROUND/AIMS
Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types in Mongolia over the last decade.
METHODS
The cohort comprised 546 consecutive patients clinically diagnosed with acute viral hepatitis from January 2012 to December 2014 in Ulaanbaatar Hospital, Mongolia. A time trend analysis investigating the change in proportion of acute hepatitis A virus, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis delta virus (HDV) infection among the cohort with respect to a previous published study was undertaken.
RESULTS
Acute hepatitis A, B and C was diagnosed in 50.9%, 26.2% and 6.0% of the cohort. Notably, 16.8% of the cohort had a dual infection. The etiologies of acute viral hepatitis were varied by age groups. The most common cause of acute viral hepatitis among 2-19 year olds was hepatitis A, HBV and superinfection with HDV among 20-40 year olds, and HCV among 40-49 year olds. Patients with more than one hepatitis virus infection were significantly older, more likely to be male and had a higher prevalence of all risk factors for disease acquisition. These patients also had more severe liver disease at presentation compared to those with mono-infection.
CONCLUSIONS
Acute viral hepatitis is still prevalent in Mongolia. Thus, the need for proper infection control is increasing in this country.
Topics: Acute Disease; Adolescent; Adult; Antibodies, Viral; Asian People; Child; Child, Preschool; Hepatitis A; Hepatitis B; Hepatitis C; Hepatitis D; Humans; Immunoglobulin M; Middle Aged; Mongolia; Prevalence; Risk Factors; Young Adult
PubMed: 28535669
DOI: 10.3350/cmh.2016.0055 -
International Journal of Molecular... Sep 2020Hepatitis A virus (HAV) infection occasionally leads to a critical condition in patients with or without chronic liver diseases. Acute-on-chronic liver disease includes... (Review)
Review
Hepatitis A virus (HAV) infection occasionally leads to a critical condition in patients with or without chronic liver diseases. Acute-on-chronic liver disease includes acute-on-chronic liver failure (ACLF) and non-ACLF. In this review, we searched the literature concerning the association between HAV infection and chronic liver diseases in PubMed. Chronic liver diseases, such as metabolic associated fatty liver disease and alcoholic liver disease, coinfection with other viruses, and host genetic factors may be associated with severe hepatitis A. It is important to understand these conditions and mechanisms. There may be no etiological correlation between liver failure and HAV infection, but there is an association between the level of chronic liver damage and the severity of acute-on-chronic liver disease. While the application of an HAV vaccination is important for preventing HAV infection, the development of antivirals against HAV may be important for preventing the development of ACLF with HAV infection as an acute insult. The latter is all the more urgent given that the lives of patients with HAV infection and a chronic liver disease of another etiology may be at immediate risk.
Topics: Animals; End Stage Liver Disease; Endoplasmic Reticulum Chaperone BiP; Hepatitis A; Hepatitis A virus; Humans
PubMed: 32887515
DOI: 10.3390/ijms21176384 -
Clinical and Molecular Hepatology Sep 2017Hepatitis A virus is one of the most frequent causes of foodborne infection, which is closely associated with sanitary conditions and hygienic practices. The clinical... (Review)
Review
Hepatitis A virus is one of the most frequent causes of foodborne infection, which is closely associated with sanitary conditions and hygienic practices. The clinical spectrum of acute hepatitis A is wide, ranging from mild case without any noticeable symptoms to severe case with acute liver failure leading to mortality. The severity and outcome are highly correlated with age at infection. In developing countries, most people are infected in early childhood without significant symptom. Ironically, in area where sanitary condition has improved rapidly, adults who do not have immunity for viral hepatitis A (VH-A) in early childhood is accumulating. Adults without immunity are exposed to risks of symptomatic disease and large outbreaks in society. In Korea, where hygiene has improved rapidly, acute hepatitis A is a significant health burden that needs to be managed with nationwide health policy. The incidence of symptomatic VH-A has increased since 2000 and peaked in 2009. Korea has designated hepatitis A as a group 1 nationally notifiable infectious disease in 2001. Since 2001, mandatory surveillance system has been established to detect every single case of acute hepatitis A. Universal, nationwide vaccination program for newborns was introduced in 2015. In this review, we will present the current epidemiologic status of viral hepatitis A, and evaluate the effectiveness of the current nationwide strategies for the control of viral hepatitis A in Korea. Furthermore, we presented some action proposals that can help eliminate viral hepatitis A, which is a significant health burden in Korea.
Topics: Age Factors; Antibodies, Viral; Hepatitis A; Humans; Military Personnel; Republic of Korea; Risk; Seroepidemiologic Studies
PubMed: 28942621
DOI: 10.3350/cmh.2017.0034