Hepatitis A Virus Infection Research Articles

Local and systemic autoimmune manifestations linked to hepatitis A infection.

Hepatitis A virus (HAV) represents a global burdening infectious agent causing in the majority of cases a self-limiting acute icteric syndrome, the outcome is related to the hepatic substrate and the potential pre-existing damage, whereas a plethora of extra-hepatic manifestations has also been reported. Despite the absence of post- HAV chronicity it has been associated with an additional burden on existing chronic liver diseases. Moreover, the induced immune response and the antigenic molecular mimicry are considered as triggering factors of autoimmunity with regional and distal impact. Diseases such as autoimmune hepatitis, Guillain-Barré syndrome, rheumatoid arthritis, Still's syndrome, Henoch-Schönlein purpura, autoimmune hemolytic anemia, antiphospholipid syndrome, systematic lupus erythematosus or cryoglobulinemic vasculitis have been described in patients with HAV infection. Although the exact mechanisms remain unclear, this review aims to accumulate and clarify the pathways related to this linkage.

Molecular epidemiology and characterization of endemic, epidemic and imported hepatitis A virus (HAV) strains in Hungary (2003-2022).

Hepatitis A virus (HAV) is one of the most important etiological agents of acute viral hepatitis but comprehensive molecular epidemiological study with chrono-phylogeographical data are not available from Hungary.Between 2003 and 2022, a total of 8,307 HAV infections were registered officially in Hungary of which 400 (4.8%) HAV IgM antibody-positive serum samples were collected countrywide. HAV genomic RNA was successfully detected in 216/400 (54%) sera by RT-PCR subsequently confirmed by sequencing. The complete nucleotide sequences of VP1 region were determined in 32 representative HAV strains. Based on the sequence analysis, 150 (69.4%) strains were characterized as HAV sub-genotype IA and 66 (30.6%) as sub-genotype IB, respectively. Based on the combined epidemiological and molecular data, epidemic, endemic, and imported HAV strains were also characterized. The first two registered countrywide outbreaks started among men-sex-with men (MSM) in 2011 (sub-genotype IA) and 2021 (sub-genotype IB), the continuously circulating endemic/domestic HAV strain (sub-genotype IA) in East Hungary and the travel-related sub-genotype IB strains from Egypt should be highlighted. All HAV strains are deposited in the HAVNET database (https://www.rivm.nl/en/havnet).In this 20-year-long comprehensive molecular epidemiological study, we report the genetic characterization and geographic distribution of endemic, epidemic and imported HAV strains for the first time in Hungary with continuous co-circulation of sub-genotypes IA and IB HAV strains since 2003. These data provide basic information about the HAV situation in the country in an international context and can promote more effective national public health intervention strategies for the prevention of HAV transmissions and infections.

Synergistic effects of sequential treatment using disinfectant and e-beam for inactivation of hepatitis a virus on fresh vegetables

Hepatitis A virus (HAV) has adversely affected public health worldwide, causing an economic burden on many countries. Fresh vegetables are reported as a source of HAV infections during production, harvesting, and distribution, which cause the emergence of foodborne illnesses. Therefore, in this study, the synergistic effects of chemical (sodium hypochlorite [NaOCl] and chlorine dioxide [ClO2]) and physical (electron-beam [e-beam] irradiation) sequential treatment for HAV inactivation on fresh vegetables were investigated, and the physicochemical quality changes of vegetables were evaluated after each treatment. On bell pepper and cucumber sequentially treated with NaOCl (50–500 ppm) and e-beam (1–5 kGy), the HAV titer was reduced by 0.19–4.69 and 0.28–4.78 log10 TCID50/mL, respectively. Sequential treatment with ClO2 (10–250 ppm) and e-beam (1–5 kGy) reduced the HAV titer on bell pepper and cucumber by 0.41–4.78 and 0.26–4.80 log10 TCID50/mL, respectively. The sequential treatments steadily decreased the HAV titers on each food by a significant difference (p < 0.05) compared to the controls. The treatment combinations of 500 ppm NaOCl and 3 kGy (e-beam) on bell pepper and 150 ppm NaOCl and 1 kGy (e-beam) on cucumber provided maximum synergistic effects. It was also found that sequential treatment with 50 ppm ClO2 and 5 kGy (e-beam) on bell pepper and 10 ppm ClO2 and 5 kGy (e-beam) on cucumber most efficiently inactivated HAV. Additionally, bell pepper and cucumber showed no significant quality changes (p < 0.05) after the treatment. Therefore, the sequential treatment with NaOCl or ClO2 and e-beam is expected to effectively control HAV on fresh vegetables without changing the food quality compared to either treatment alone.

Identification of Mulberrofuran as a potent inhibitor of hepatitis A virus 3Cpro and RdRP enzymes through structure-based virtual screening, dynamics simulation, and DFT studies.

Hepatitis is a medical condition characterized by inflammation of the liver. It is commonly caused by the hepatitis viruses A, B, C, D, and E. Hepatitis A virus (HAV) is highly contagious and can spread from infected individuals, through contaminated food, blood, or can also be water-borne. As per the statistics of World Health Organization (WHO), HAV infects about 1.4 million individuals each year globally. In this research work, we have focused on identifying natural product-based potential inhibitors for the two major enzymes of HAV namely 3C proteinase (3Cpro) and RNA-directed RNA polymerase (RdRP). The enzyme 3Cpro plays an important role in proteolytic activity that promotes viral maturation and infectivity. RNA-directed RNA polymerase facilitate viral replication and transcription. Structure-based virtual screening was carried out using NPACT database that contains a collection of 1574 curated plant-derived natural compounds that are validated by experiments. The screening procedure identified the phytochemical Mulberrofuran W, which could bind to both the targets 3Cpro and RdRP. The phytochemical Mulberrofuran W also had better binding affinity compared to the control compounds atropine and pyridinyl ester, which are previously identified inhibitors of HAV 3Cpro and RdRP, respectively. The Mulberrofuran W bound 3Cpro and RdRP complexes were subjected to 200ns molecular dynamics simulations and were found to be stable and interacting with the active site of the enzymes throughout the course of complex MD simulations. In addition to DFT, MMGBSA studies were also performed to validate the identified potential inhibitor further. The identified phytochemical Mulberrofuran W can be considered as a new potential drug candidate and could be taken up for experimental evaluation against HAV infection.

Hepatitis A seroprevalence, vaccination status and demographic determinants in children and adolescents in Germany, 2014–2017, a population-based study

Children play an important role in hepatitis A virus (HAV) transmission but, due to frequent asymptomatic or mild courses, these infections are underrecognized in routine surveillance. Here, we analyzed hepatitis A (HA) seroprevalence, vaccination status and demographic determinants and estimated previous HAV infections in a cross-sectional population-based study of children and adolescents with residence in Germany 2014–2017, performing weighted univariable and multivariable logistic regression. Of 3567 participants aged 3–17 years, serological results were available for 3013 (84.5%), vaccination records for 3214 (90.1%) and both for 2721 (76.3%). Of 2721 with complete results, 467 (17.2%) were seropositive, thereof 412 (15.1%) with and 55 (2.0%) without previous HA vaccination, indicating previous HAV infection. Seropositivity was associated with age, residence in Eastern states, high socioeconomic status and migration background with personal migration experience. Participants with migration background and personal migration experience also had the highest odds ratios for previous HAV infection. Germany remains a country with very low HA endemicity. The current vaccination recommendations focusing on individuals with a high risk for HAV exposure (e.g. travelers to endemic countries) or severe disease appear appropriate. Migration and travel patterns as well as the endemicity in other countries influence the domestic situation, warranting further monitoring.

Impact of prior HBV, HAV, and HEV infection on non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. The association between prior hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis E virus (HEV) infection and NAFLD remains unclear. We utilized the 2017-2020 National Health and Nutrition Examination Survey (NHANES) and performed multivariable logistic regression analyses to examine the association of prior HBV, HAV and HEV infection with NAFLD, as well as high risk non-alcoholic steatohepatitis (NASH) and liver fibrosis. Our analysis included 2565 participants with available anti-HBc serology results, 1480 unvaccinated participants with anti-HAV results, and 2561 participants with anti-HEV results. Among participants with NAFLD, the age-adjusted prevalence of prior HBV, HAV and HEV infection was 3.48%, 32.08% and 7.45%, respectively. Prior infection with HBV, HAV and HEV was not associated with NAFLD (cut-off 285 dB/m) [aOR: 0.99 (95% CI, 0.77-1.29), 1.29 (95% CI, 0.95-1.75), and 0.94 (95% CI, 0.70-1.27), respectively] or high-risk NASH [aOR 0.72 (95% CI, 0.45-1.17), 0.92 (95% CI, 0.55-1.52), and 0.89 (95% CI, 0.41-1.94), respectively]. Participants with anti-HBc and anti-HAV seropositivity were more likely to have significant fibrosis [aOR: 1.53 (95% CI, 1.05-2.23) and 1.69 (95% CI, 1.16-2.47), respectively]. The odds of significant fibrosis are 53%, and 69% greater for participants with prior history of HBV and HAV infection. Healthcare providers should prioritize vaccination efforts and employ a tailored approach to NAFLD in patients with prior viral hepatitis and especially HBV or HAV infection to limit disease-related outcomes.

Masitinib Inhibits Hepatitis A Virus Replication.

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.

EVALUATION OF THE RATE OF HEPATITIS A IMMUNITY IN A SMALL CITY AFTER THE VACCINATION PROGRAM: ONE CENTER EXPERIENCE

Purpose: Hepatitis A is an infectious disease caused by hepatitis A virus (HAV). Symptomatic infection causes health care costs with loss of labor and school time. HAV outbreaks may cause economic problems by disrupting trade and tourism. The aim of this study is to determine the rate of immunity against HAV infection in a sample of pediatric population.&#x0D; Methods: The study group consisted of all children who underwent anti-HAV IgG evaluation for any reason between January 1, 2012 and December 31, 2020. The data about age, date of birth, sex, residence, vaccination status were retrospectively collected from the hospital record system. Anti-HAV IgG status was determined by chemiluminescent microparticle immunassay kits. The statistical analyses were presented with descriptive methods. &#x0D; Results: Overall 1189 children aged 1-17 years old enrolled to the study. The rate of anti HAV IgG seropositivity was 41.2% in the whole study group. The rates of completed vaccination scheme and seropositivity were 10.7% and 92.2%. Natural immunity rate was 32.6%.&#x0D; Conclusion: The 7-17 age group was found to be susceptible to the acute infection, they were considered as the new target population of vaccination. Vaccination seemed to be the most effective way of providing seropositivity to get rid of acute infection risk and eliminating geographic and socioeconomic differences.

The Role of Quasi-Enveloped Hepatitis A Virus in Hepatitis A Virus⟉nfection

Hepatitis A virus (HAV) infection affects the global population and is responsible for acute hepatitis. Although most acute HAV infections can resolve spontaneously, there are about 15,000–30,000 deaths occurring annually worldwide. Therefore, it is important to study the mechanism of HAV infection. Recent studies have shown that HAV can be cloaked in the host membrane and exit cells nonlytically. This unique form of HAV is called quasi-enveloped HAV (eHAV) and is infectious and resistant to neutralizing antibodies. eHAV makes HAV different from many picornaviruses and provides a new pathway to HAV infection. In this review, we briefly summarize the characteristics and functions of eHAV in HAV infection.

Comparative Analysis on Clinical Characteristics Among Patients with Acute Hepatitis A Virus (HAV) and Patients with Acute Hepatitis E Virus (HEV): A Single-Center Retrospective Study from Bulgaria.

The acute viral hepatitis was one of the most common conditions in daily clinical practice varying in different parts of the world. The aim of the present study was to perform a comparative analysis on clinical characteristics among patients with acute hepatitis A virus (HAV) infection and patients with acute hepatitis E virus (HEV) infection admitted to the Military Medical Academy (MMA), Sofia, Bulgaria. A retrospective study was performed at MMA, between 1 January 2016 and 31 December 2021. The etiological diagnosis was confirmed by enzyme-linked immunosorbent assay (ELISA) HAV/HEV IgM serology assays. The current survey included 231 patients with mean age 45.11 ± 16.08 years (95% confidence interval: 43.04-47.19). According to the case definition, inclusion and exclusion criteria, persons were divided into two groups: patients with acute HAV infection (68.4%; 158/231) and patients with acute HEV infection (31.6%; 73/231). Males with HEV had 3.091 times the odds of comorbidity "hypertension" than males with HAV (p = 0.032). There were almost equal odds of increased ALT (odds ratio = 0.999; p = 0.003) in men with HEV and men with HAV. Females with HEV had 5.161 times the odds of comorbidity "hypertension" compared with females with HAV (p = 0.049). We found almost equal odds for elevated ALT in women with HEV and women with HAV (OR = 0.999; p = 0.025). In the non-elderly group (<60-year-old), HEV individuals had 4.544 and 10.560 times the odds of comorbidities "hypertension" and "cardiovascular diseases" compared with HAV patients (p < 0.05). We found almost equal odds for elevated ALT in HEV patients and HAV participants (OR = 0.998; p = 0.002). The results from the current study may support the physicians daily care for patients with acute HAV and acute HEV.

Comparison of HAV and HCV infections in vivo and in vitro reveals distinct patterns of innate immune evasion and activation

Hepatitis A virus (HAV) infections are considered not to trigger innate immunity invivo, in contrast to hepatitis C virus (HCV). This lack of induction has been imputed to strong interference by HAV proteases 3CD and 3ABC. We aimed to elucidate the mechanisms of immune activation and counteraction by HAV and HCV invivo and invitro. Albumin-urokinase-type plasminogen activator/severe combined immunodeficiency (Alb/uPA-SCID) mice with humanised livers were infected with HAV and HCV. Hepatic cell culture models were used to assess HAV and HCV sensing by Toll-like receptor 3 and retinoic acid-inducible gene I/melanoma differentiation-associated protein 5 (RIG-I/MDA5), respectively. Cleavage of the adaptor proteins TIR-domain-containing adapter-inducing interferon-β (TRIF) and mitochondrial antiviral-signalling protein (MAVS) was analysed by transient and stable expression of HAV and HCV proteases and virus infection. We detected similar levels of interferon-stimulated gene induction in hepatocytes of HAV- and HCV-infected mice with humanised liver. In cell culture, HAV induced interferon-stimulated genes exclusively upon MDA5 sensing and depended on LGP2 (laboratory of genetics and physiology 2). TRIF and MAVS were only partially cleaved by HAV 3ABC and 3CD, not sufficiently to abrogate signalling. In contrast, HCV NS3-4A efficiently degraded MAVS, as previously reported, whereas TRIF cleavage was not detected. HAV induces an innate immune response in hepatocytes via MDA5/LGP2, with limited control of both pathways by proteolytic cleavage. HCV activates Toll-like receptor 3 and lacks TRIF cleavage, suggesting that this pathway mainly contributes to HCV-induced antiviral responses in hepatocytes. Our results shed new light on the induction of innate immunity and counteraction by HAV and HCV. Understanding the mechanisms that determine the differential outcomes of HAV and HCV infections is crucial for the development of effective therapies. Our study provides insights into the interplay between these viruses and the host innate immune response invitro and invivo, shedding light on previously controversial or only partially investigated aspects. This knowledge could tailor the development of new strategies to combat HCV persistence, as well as improve our understanding of the factors underlying successful HAV clearance.

Simple and feasible detection of hepatitis a virus using reverse transcription multienzyme isothermal rapid amplification and lateral flow dipsticks without standard PCR laboratory

Hepatitis A virus (HAV) is mainly transmitted via contaminated food and water. HAV infection is a major global public health problem. Thus, developing a simple, rapid detection method is crucial for containing HAV epidemics, particularly in developing regions with limited laboratory resources. This study established a feasible HAV detection solution by combining reverse transcription multienzyme isothermal rapid amplification (RT-MIRA) and lateral flow dipstick (LFD) strips. Primers targeting the conserved 5’UTR sequence of HAV were used in the RT-MIRA-LFD assay. RNA extraction was enhanced by obtaining RNA directly from the centrifuged supernatant. Our study found that MIRA amplification could be finished in 12 min at 37 °C and naked-eye observation of the LFD strips in 10 min. The detection sensitivity of this method reached 1 copy/μl. RT-MIRA-LFD was compared to conventional RT-PCR using 35 human blood samples. The accuracy of the RT-MIRA-LFD method was 100%. The convenience, sensitivity, and rapidness of this detection method could provide a considerable advantage for diagnosing and controlling HAV infection, especially in regions with limited medical resources.

Hepatitis A virus infection in Brazilian correctional facilities.

Hepatitis A virus (HAV) infection is transmitted by the fecal-oral route, through interpersonal contact and ingestion of contaminated food or water. Prisoners are at higher risk of acquiring HAV infection mainly due to the environment of closed penal institutions and socioeconomic conditions. This study aims to determine the seroprevalence of anti-HAV and its associated risk factors among inmates from twelve prisons in Central Brazil. A cross-sectional study was conducted between March 2013 and March 2014. A total of 580 prisoners participated in the study. The participant's samples were tested for Total and IgM anti-HAV antibodies by electrochemiluminescence immunoassay (ECLIA). Risk factors associated with anti-HAV seropositivity were also analyzed. The prevalence rate of HAV exposure was 88.1% (95% CI: 85.5-90.7). No sample had a positive reaction to IgM anti-HAV. Increasing age, low level of education, and being imprisoned in Corumbá city were independently associated with HAV exposure among prisoners. To prevent the burden of the disease, vaccination strategies should be considered for susceptible prisoners in Central Brazil.

SiRNAs to Knockdown Antiviral Chemokine-related Genes in FRhK-4 Cells

The objective of this study was to generate small interfering RNA (siRNA) to knockdown antiviral chemokine-related genes in fetal rhesus monkey kidney (FRhK-4) cells. We generated siRNA duplexes to suppress antiviral chemokines like CXCL10 and CCL4 in FRhK-4 cells by downregulating interferon regulatory factor (IRF) 3 and IRF7. Three siRNA duplexes (si-F-IRF3-1, si-F-IRF3-2, and si-F-IRF3-3) targeting IRF3, and one siRNA duplex (si-F-IRF7) targeting IRF7 were generated. A nontarget siRNA duplex was used as the negative control. The nontarget or target siRNA duplexes (si-F-IRF3-1, si-F-IRF3-2, si-F-IRF3-3, and si-F-IRF7) were transfected into FRhK-4 cells using transfection reagents, and they were then incubated at 37°C for 6 h with 5% CO2. After 6 h, the medium was removed, and fresh medium was added to each cell, and they were then incubated at 37°C for 48 h with 5% CO2. The transfected FRhK-4 cells were infected with hepatitis A virus (HAV) HM-175/18f (viral titer: 105 PFU/mL) and incubated at 37°C for 3 h with 5% CO2 for HAV propagation. The expression levels of chemokines, including CXCL10 and CCL4, under the regulation of IRF3 and IRF7 in the transfected FRhK-4 cells were measured using quantitative real-time polymerase chain reaction after 3 h of HAV infection. The results indicated that CXCL10 and CCL4 expression levels were decreased in FRhK-4 cells transfected with si-F-IRF3-1, si-F-IRF3-3, or si-F-IRF7 (p < 0.05) compared to those in the negative control. These results indicate that si-F-IRF3-1 and si-F-IRF3-3, and si-F-IRF7 successfully knocked down IRF3 and IRF7 in FRhK-4 cells, respectively and suppressed antiviral chemokines. These siRNAs could be used to suppress antiviral chemokines in FRhK-4 cells.

Prolonged Cholestasis in Patient with Acute HAV Infection

Background: Hepatitis A virus (HAV) is a virus which infects yearly more than 1.5 million persons worldwide and is usually spread through contaminated food and water. Most HAV infection in children under the six years of age are asymptomatic and they develop lifelong immunity. However, HAV infection in older children and adults often symptomatic with development of jaundice, nausea, vomiting, poor appetite, fever, fatigue, abdominal pain, etc. most of those infected patients usually fully recovering from HAV infection naturally within 2 months, it has not been a cause for major concern of public health). With more and more patients suffering from hepatitis A, there is also increase in the number of patients suffering from unusual presentation of HAV infection also. Most hepatitis A patients tend to recover from the illness natural without any complications; however, there are occasions of serious complications among adult hepatitis A patients such as extrahepatic manifestation, acute renal failure, cholestatic hepatitis, relapsing hepatitis, prolonged course and even fulminant hepatic failure. Cholestatic hepatitis accounts for between 0.8 - 5.2% of hepatitis. Together with increasingly more cases of hepatitis A being reported, the number of patients who have cholestatic hepatitis arising from hepatitis A also has increased. The current treatment for hepatitis A is usually symptomatic treated by sufficient nutrition, vitamin supply and sufficient rest. There are also no special treatments for cholestatic hepatitis, with conservative treatment being used. Ursodeoxycholic acid (UDCA) and cholestyramine and antihistamines are used to treat skin itching caused by cholestatic hepatitis; however, there are occasions where symptoms of cholestatic hepatitis are so severe and prolong that required the use of corticosteroids to shorten the duration of symptoms and reduce hospitalization.as to call for liver transplantation. Aim: Is to show the effectiveness of corticosteroids in shorten the duration of severe symptoms and shorten hospitalization in patient with prolong severe cholestatic symptoms of acute hepatitis A virus infection.

Antiviral Efficacy of Dielectric Barrier Discharge Plasma against Hepatitis A Virus in Fresh Oyster Using PMA/RT-qPCR

The hepatitis A virus (HAV), which can be a threat to humans, can be found in oysters. Oysters need sterilization technology that does not cause quality changes because they are eaten raw. Therefore, in this study, antiviral effects and quality changes were conducted using dielectric barrier discharge plasma (DBDP). Total titers of non-PMA- and PMA-treated suspensions of HAV were reduced to 0.20–1.05 and 0.35–1.49 log10 copies/μL, respectively, after DBDP 10–60 min treatment. HAV titers on oysters were reduced to 0.20–1.11 and 0.33–1.33 log10 copies/μL, respectively, after identical an DBDP treatment of the non-PMA- and PMA-treated oysters. The HAV titers were revealed as 0.295 (=[0.25 for 30 min + 0.34 for 60 min]/2) and 0.22 (for 60 min) log10-reduction in PMA-treated suspensions and oysters, respectively, compared with the non-PMA-treated suspensions and oysters. The D1 of DBDP in PMA-treated suspensions and oysters were 39.99 and 46.73 min, respectively. There was no difference in the pH of oysters after DBDP treatment compared to the non-treated control. There were some changes in the hardness of the DBDP-treated oysters, which was due to oyster individual differences rather than the DBDP treatment. In conclusion, DBDP treatment did not affect oyster quality and PMA was able to distinguish HAV infectivity.

Hepatitis in India: challenges, efforts, and recommendations

Hepatitis in India: challenges, efforts, and recommendations

Pediatric Hepatitis A: A Case Report

Background: Hepatitis A is a systemic infection which predominantly inflame the liver due to Hepatitis-A-Virus (HAV) infection. Developing countries have higher prevalence of this disease because of poor sanitation and environment. The transmission of HAV is fecal-oral via contaminated foods or beverages. Case: A 14-year-old boy visited emergency department with yellowish skin on body, nausea, fever, and liver enlargement. He had a bad habit of consuming unhealthy street-foods. Hepatitis A was diagnosed after history taking, physical examination and laboratory testing. Serology test was performed with positive Anti HAV IgM to confirm the disease. Liver enzymes, and bilirubin level were also increased in this patient. Discussion: The transmission of HAV is through fecal-oral via contaminated foods or beverages. This disease can be prevented by having good personal hygiene, avoiding contaminated food, with good access to clean water and environmental sanitation. Habit of consuming street foods is a risk factor of developing HAV infection. The clinical manifestation of HAV infection includes jaundice, nausea, decreased appetite, and vomiting. Conclusion: Diagnosis of hepatitis A requires careful history taking, physical examination and laboratory evaluation. Hepatitis A is a self-limiting disease and currently there is no specific treatment to cure this disease. Supportive treatment, hepato-protector and vitamin supplementation will improve the condition.

Drug Screening for Hepatitis A Virus (HAV): Nicotinamide Inhibits c-Jun Expression and HAV Replication.

Hepatitis A virus (HAV) infection often causes acute hepatitis, which results in a case fatality rate of 0.2% and fulminant hepatitis in 0.5% of cases. However, no specific potent anti-HAV drug is available on the market to date. In the present study, we focused on inhibition of HAV internal ribosomal entry site (IRES)-mediated translation and investigated novel therapeutic drugs through drug repurposing by screening for inhibitors of HAV IRES-mediated translation and cell viability using a reporter assay and cell viability assay, respectively. The initial screening of 1,158 drugs resulted in 77 candidate drugs. Among them, nicotinamide significantly inhibited HAV HA11-1299 genotype IIIA replication in Huh7 cells. This promising drug also inhibited HAV HM175 genotype IB subgenomic replicon and HAV HA11-1299 genotype IIIA replication in a dose-dependent manner. In the present study, we found that nicotinamide inhibited the activation of activator protein 1 (AP-1) and that knockdown of c-Jun, which is one of the components of AP-1, inhibited HAV HM175 genotype IB IRES-mediated translation and HAV HA11-1299 genotype IIIA and HAV HM175 genotype IB replication. Taken together, the results showed that nicotinamide inhibited c-Jun, resulting in the suppression of HAV IRES-mediated translation and HAV replication, and therefore, it could be useful for the treatment of HAV infection. IMPORTANCE Drug screening methods targeting HAV IRES-mediated translation with reporter assays are attractive and useful for drug repurposing. Nicotinamide (vitamin B3, niacin) has been shown to effectively inhibit HAV replication. Transcription complex activator protein 1 (AP-1) plays an important role in the transcriptional regulation of cellular immunity or viral replication. The results of this study provide evidence that AP-1 is involved in HAV replication and plays a role in the HAV life cycle. In addition, nicotinamide was shown to suppress HAV replication partly by inhibiting AP-1 activity and HAV IRES-mediated translation. Nicotinamide may be useful for the control of acute HAV infection by inhibiting cellular AP-1 activity during HAV infection processes.

Hepatitis A: Viral Structure, Classification, Life Cycle, Clinical Symptoms, Diagnosis Error, and Vaccination.

Hepatitis A virus (HAV) is one of the well-known viruses that cause hepatitis all around the globe. Although this illness has decreased in developed countries due to extensive immunization, numerous developing and under-developed countries are struggling with this virus. HAV infection can be spread by oral-fecal contact, and there are frequent epidemics through nutrition. Improvements in socioeconomic and sanitary circumstances have caused a shift in the disease's prevalence worldwide. Younger children are usually asymptomatic, but as they become older, the infection symptoms begin to appear. Symptoms range from slight inflammation and jaundice to acute liver failure in older individuals. While an acute infection may be self-limiting, unrecognized persistent infections, and the misapplication of therapeutic methods based on clinical guidelines are linked to a higher incidence of cirrhosis, hepatocellular carcinoma, and mortality. Fortunately, most patients recover within two months of infection, though 10-15% of patients will relapse within the first six months. A virus seldom leads to persistent infection or liver damage. The mainstay of therapy is based on supportive care. All children from 12-23 months, as well as some susceptible populations, should receive routine vaccinations, according to the Centers for Disease Control and Prevention and the American Academy of Pediatrics. Laboratory diagnosis of HAV is based on antigen detection, checking liver enzyme levels, and antibody screening. Furthermore, polymerase chain reaction (PCR) technology has identified HAV in suspected nutrition sources; therefore, this technique is used for preventative measures and food-related laws.