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Annals of Saudi Medicine 2011Published data on oxidative stress in children with acute hepatitis A are still very scarce. This study aims to evaluate the oxidant/antioxidant status of these patients.
BACKGROUND AND OBJECTIVES
Published data on oxidative stress in children with acute hepatitis A are still very scarce. This study aims to evaluate the oxidant/antioxidant status of these patients.
DESIGN AND SETTING
Prospective, case-control study, over 2.5 years in patients under hospitalized and ambulatory care.
PATIENTS AND METHODS
The levels of a whole-blood antioxidant, reduced glutathione; and plasma antioxidants, β-carotene, retinol, ascorbic acid, α-tocopherol; and the biomarker of oxidative stress, malondialdehyde, were evaluated in 50 pediatric patients (age range, 5-16 years; 29 males and 21 females) with acute hepatitis A and in 50 healthy children as control subjects (age range, 5-16 years; 25 males and 25 females).
RESULTS
Plasma levels of reduced glutathione, β-carotene, retinol, α-tocopherol and ascorbic acid were significantly lower, while malondialdehyde plasma levels were significantly increased in the patient group when compared to the controls (P<.0001 for all parameters).
CONCLUSIONS
Our findings show that pediatric patients with acute hepatitis A were influenced by oxidative stress, resulting in significantly lower levels of plasma antioxidants and increased lipid peroxidation. In the absence of other therapeutic options, antioxidant vitamin supplements could be added to the therapy for these patients to help reestablish the oxidant status balance. Further investigations to confirm this suggestion are recommended.
Topics: Acute Disease; Adolescent; Antioxidants; Case-Control Studies; Child; Child, Preschool; Female; Hepatitis A; Humans; Lipid Peroxidation; Male; Oxidative Stress; Prospective Studies
PubMed: 21623054
DOI: 10.4103/0256-4947.81538 -
Archives of Disease in Childhood Feb 1989Over a period of three and a half years, 348 consecutive children with acute hepatitis were studied. There were 205 boys and 143 girls aged from 3 months to 12 years...
Over a period of three and a half years, 348 consecutive children with acute hepatitis were studied. There were 205 boys and 143 girls aged from 3 months to 12 years old. The most common type was hepatitis A, of which there were 281 cases, 81% of the total; there were 41 in the under 4 years old age group (63% of that group), 99 in the 5-8 year old age group (87% of that group) and 141 in the 8-12 year old age group (83% of that group). Hepatitis B occurred in 29 (8% of the total), and non-A, non-B hepatitis occurred in 35 (10%). All the children with hepatitis A and all but one with hepatitis B recovered. There were three deaths from fulminant hepatitis, one in the group with hepatitis B and two with non-A, non-B. Clearance of the hepatitis B surface antigen was fast, by six months 26 patients having cleared the antigen and 21 (77%) being positive for hepatitis B surface antibody. One patient became a carrier of hepatitis B surface antigen.
Topics: Acute Disease; Child; Child, Preschool; Female; Hepatitis A; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis C; Hepatitis, Viral, Human; Hong Kong; Humans; Infant; Male; Time Factors
PubMed: 2494951
DOI: 10.1136/adc.64.2.211 -
PloS One 2011In sub-Saharan Africa, Plasmodium falciparum and hepatitis A (HAV) infections are common, especially in children. Co-infections with these two pathogens may therefore...
BACKGROUND
In sub-Saharan Africa, Plasmodium falciparum and hepatitis A (HAV) infections are common, especially in children. Co-infections with these two pathogens may therefore occur, but it is unknown if temporal clustering exists.
MATERIALS AND METHODS
We studied the pattern of co-infection of P. falciparum malaria and acute HAV in Kenyan children under the age of 5 years in a cohort of children presenting with uncomplicated P. falciparum malaria. HAV status was determined during a 3-month follow-up period.
DISCUSSION
Among 222 cases of uncomplicated malaria, 10 patients were anti-HAV IgM positive. The incidence of HAV infections during P. falciparum malaria was 1.7 (95% CI 0.81-3.1) infections/person-year while the cumulative incidence of HAV over the 3-month follow-up period was 0.27 (95% CI 0.14-0.50) infections/person-year. Children with or without HAV co-infections had similar mean P. falciparum asexual parasite densities at presentation (31,000/µL vs. 34,000/µL, respectively), largely exceeding the pyrogenic threshold of 2,500 parasites/µL in this population and minimizing risk of over-diagnosis of malaria as an explanation.
CONCLUSION
The observed temporal association between acute HAV and P. falciparum malaria suggests that co-infections of these two hepatotrophic human pathogens may result from changes in host susceptibility. Testing this hypothesis will require larger prospective studies.
Topics: Acute Disease; Child, Preschool; Female; Hepatitis A; Hepatitis A Antibodies; Humans; Kenya; Malaria, Falciparum; Male; Time Factors
PubMed: 21754982
DOI: 10.1371/journal.pone.0021013 -
LaeknabladidHepatitis A virus (HAV) epidemics occurred repeatedly in Iceland in the early 20th century, but since then few cases have been reported and no epidemics since 1952. The...
INTRODUCTION
Hepatitis A virus (HAV) epidemics occurred repeatedly in Iceland in the early 20th century, but since then few cases have been reported and no epidemics since 1952. The latest Icelandic studies on HAV from around 1990 showed low incidence of infection and de-- creasing prevalence of antibodies. The objective of this study was to determine the incidence, clinical presentation and origin of HAV, abroad or in Iceland.
MATERIAL AND METHODS
A retrospective search was undertaken on all patients with positive anti-HAV IgM during the 11 years period of 2006-2016 in the virological database of the National University Hospital of Iceland. Clinical data was collected from medical records on symptoms at diagnosis, blood test results and possible route of transmission.
RESULTS
A total of 12 individuals were diagnosed with acute hepatitis A during the period and 6691 HAV total andibody tests and 1984 HAV IgM antibody tests were performed. Nine (75%) had been abroad within 7 weeks from initial symptoms. The most common symptoms were jaundice (83%), fever (67%) and nausea and/or vomiting (58%). 50% were admitted to a hospital. 42% had elevated INR/PT. Everyone sur-vived without complications.
CONCLUSION
Annually, approximately one case of acute hepatitis A was diagnosed in Iceland during the study period but a very high number of antibody tests were performed. The majority of cases occurred among individuals who had recently been abroad. If patients have jaundice, fever and nausea, testing for HAV infection should be undertaken. HAV is not endemic in Iceland.
Topics: Biomarkers; Databases, Factual; Hepatitis A; Hepatitis A Antibodies; Hepatitis A virus; Hospitals, University; Humans; Iceland; Immunoglobulin M; Incidence; Predictive Value of Tests; Retrospective Studies; Risk Factors; Time Factors; Travel
PubMed: 29493530
DOI: 10.17992/lbl.2018.03.176 -
Amantadine and Rimantadine Inhibit Hepatitis A Virus Replication through the Induction of Autophagy.Journal of Virology Sep 2022Hepatitis A virus (HAV) infection is a major cause of acute viral hepatitis worldwide. Furthermore, HAV causes acute liver failure or acute-on-chronic liver failure....
Hepatitis A virus (HAV) infection is a major cause of acute viral hepatitis worldwide. Furthermore, HAV causes acute liver failure or acute-on-chronic liver failure. However, no potent anti-HAV drugs are currently available in the clinical situations. There have been some reports that amantadine, a broad-spectrum antiviral, suppresses HAV replication . Therefore, we examined the effects of amantadine and rimantadine, derivates of adamantane, on HAV replication, and investigated the mechanisms of these drugs. In the present study, we evaluated the effects of amantadine and rimantadine on HAV HM175 genotype IB subgenomic replicon replication and HAV HA11-1299 genotype IIIA replication in cell culture infection systems. Amantadine and rimantadine significantly inhibited HAV replication at the post-entry stage in Huh7 cells. HAV infection inhibited autophagy by suppressing the autophagy marker light chain 3 and reducing number of lysosomes. Proteomic analysis on HAV-infected Huh7 cells treated by amantadine and rimantadine revealed the changes of the expression levels in 42 of 373 immune response-related proteins. Amantadine and rimantadine inhibited HAV replication, partially through the enhancement of autophagy. Taken together, our results suggest a novel mechanism by which HAV replicates along with the inhibition of autophagy and that amantadine and rimantadine inhibit HAV replication by enhancing autophagy. Amantadine, a nonspecific antiviral medication, also effectively inhibits HAV replication. Autophagy is an important cellular mechanism in several virus-host cell interactions. The results of this study provide evidence indicating that autophagy is involved in HAV replication and plays a role in the HAV life cycle. In addition, amantadine and its derivative rimantadine suppress HAV replication partly by enhancing autophagy at the post-entry phase of HAV infection in human hepatocytes. Amantadine may be useful for the control of acute HAV infection by inhibiting cellular autophagy pathways during HAV infection processes.
Topics: Amantadine; Antiviral Agents; Autophagy; Cell Line; Hepatitis A; Hepatitis A Antibodies; Hepatitis A virus; Humans; Proteomics; Rimantadine; Virus Replication
PubMed: 36040176
DOI: 10.1128/jvi.00646-22 -
Postgraduate Medical Journal Jul 1971Acute fulminant hepatitis leads to complex biochemical and circulatory disturbances including coma. These can be predicted to some extent by knowledge of the functions... (Review)
Review
Acute fulminant hepatitis leads to complex biochemical and circulatory disturbances including coma. These can be predicted to some extent by knowledge of the functions of the normal liver cells. Ineffective haemostasis, coma, hypoglycaemia, electrolyte abnormalities, hypotension and renal circulatory failure are particularly important. Management should be governed by the abnormalities found in the individual patient. Fluid overload and sedation must be avoided. More complex methods of temporary hepatic support such as exchange transfusion or perfusion of the isolated pig's liver should only be considered after simpler methods of correction have been attempted for a reasonable period of time and found wanting. The prognosis of acute hepatocellular failure reaching the stage of deep coma is very poor, the mortality being about 80-90%.
Topics: Acute Disease; Acute Kidney Injury; Adrenal Cortex Hormones; Animals; Blood Coagulation Disorders; Chemical and Drug Induced Liver Injury; Citric Acid Cycle; Exchange Transfusion, Whole Blood; Extracorporeal Circulation; Hepatitis; Hepatitis A; Humans; Hypoglycemia; Liver; Prognosis; Serum Albumin; Swine
PubMed: 4934637
DOI: 10.1136/pgmj.47.549.493 -
Proceedings of the National Academy of... Jul 2022Despite excellent vaccines, resurgent outbreaks of hepatitis A have caused thousands of hospitalizations and hundreds of deaths within the United States in recent years....
Despite excellent vaccines, resurgent outbreaks of hepatitis A have caused thousands of hospitalizations and hundreds of deaths within the United States in recent years. There is no effective antiviral therapy for hepatitis A, and many aspects of the hepatitis A virus (HAV) replication cycle remain to be elucidated. Replication requires the zinc finger protein ZCCHC14 and noncanonical TENT4 poly(A) polymerases with which it associates, but the underlying mechanism is unknown. Here, we show that ZCCHC14 and TENT4A/B are required for viral RNA synthesis following translation of the viral genome in infected cells. Cross-linking immunoprecipitation sequencing (CLIP-seq) experiments revealed that ZCCHC14 binds a small stem-loop in the HAV 5' untranslated RNA possessing a Smaug recognition-like pentaloop to which it recruits TENT4. TENT4 polymerases lengthen and stabilize the 3' poly(A) tails of some cellular and viral mRNAs, but the chemical inhibition of TENT4A/B with the dihydroquinolizinone RG7834 had no impact on the length of the HAV 3' poly(A) tail, stability of HAV RNA, or cap-independent translation of the viral genome. By contrast, RG7834 inhibited the incorporation of 5-ethynyl uridine into nascent HAV RNA, indicating that TENT4A/B function in viral RNA synthesis. Consistent with potent in vitro antiviral activity against HAV (IC 6.11 nM), orally administered RG7834 completely blocked HAV infection in mice, and sharply reduced serum alanine aminotransferase activities, hepatocyte apoptosis, and intrahepatic inflammatory cell infiltrates in mice with acute hepatitis A. These results reveal requirements for ZCCHC14-TENT4A/B in hepatovirus RNA synthesis, and suggest that TENT4A/B inhibitors may be useful for preventing or treating hepatitis A in humans.
Topics: Animals; Antiviral Agents; Chromosomal Proteins, Non-Histone; DNA-Directed DNA Polymerase; Hepatitis A; Hepatitis A virus; Humans; Intrinsically Disordered Proteins; Mice; Mice, Mutant Strains; RNA Nucleotidyltransferases; RNA, Viral; Receptor, Interferon alpha-beta; Virus Replication
PubMed: 35867748
DOI: 10.1073/pnas.2204511119 -
Proceedings of the National Academy of... Jul 2011Hepatitis A virus (HAV) is an hepatotropic human picornavirus that is associated only with acute infection. Its pathogenesis is not well understood because there are few... (Comparative Study)
Comparative Study
Hepatitis A virus (HAV) is an hepatotropic human picornavirus that is associated only with acute infection. Its pathogenesis is not well understood because there are few studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by quantitative RT-PCR and examining critical aspects of the innate immune response including intrahepatic IFN-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), an hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I IFN-stimulated genes in the liver compared with chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal IFN-stimulated gene 15 and IFIT1 responses peaked 1-2 wk after HAV challenge and then subsided despite continuing high hepatic viral RNA. An acute inflammatory response at 3-4 wk correlated with the appearance of virus-specific antibodies and apoptosis and proliferation of hepatocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for significantly longer (35 to >48 wk) than HCV RNA in animals with acute resolving HCV infection (10-20 wk). Collectively, these findings indicate that HAV is far stealthier than HCV early in the course of acute resolving infection. HAV infections represent a distinctly different paradigm in virus-host interactions within the liver.
Topics: Acute Disease; Animals; Base Sequence; DNA Primers; Gene Expression; Gene Expression Profiling; Hepacivirus; Hepatitis A; Hepatitis A virus; Hepatitis C; Host-Pathogen Interactions; Humans; Immunity, Innate; Interferon Type I; Liver; Pan troglodytes; RNA, Viral; Time Factors
PubMed: 21690403
DOI: 10.1073/pnas.1101939108 -
Intervirology 2017This study investigated the etiology of acute viral hepatitis and compared the clinical features of hepatitis E virus (HEV) infections with those of other acute viral... (Comparative Study)
Comparative Study
OBJECTIVES
This study investigated the etiology of acute viral hepatitis and compared the clinical features of hepatitis E virus (HEV) infections with those of other acute viral hepatitis infections in Korea.
METHODS
This study included 2,357 consecutive patients who were diagnosed with acute hepatitis, based on acute illness with jaundice or elevated alanine aminotransferase levels (>100 IU/L), between January 2007 and January 2016. Acute viral infections were observed in 23 (19.8%) patients with HEV, 49 (42.2%) patients with hepatitis A virus, 28 (24.1%) patients with hepatitis B virus, and 16 (13.8%) patients with hepatitis C virus.
RESULTS
The incidence of acute HEV infection was higher among older patients (median age: 49 years) and male patients (69.6%), and was associated with the consumption of undercooked or uncooked meat (43.5%). Half of the acute HEV infections involved underlying liver disease, such as alcoholic liver disease, chronic hepatitis B, common bile duct stones, and autoimmune hepatitis. Two HEV-infected patients were diagnosed with Guillain-Barré syndrome, although no patients developed fulminant hepatitis.
CONCLUSION
Our findings indicate that HEV infection in Korea is frequently transmitted through the consumption of raw meat and may cause acute or chronic liver disease.
Topics: Adult; Antiviral Agents; Female; Hepatitis A; Hepatitis B, Chronic; Hepatitis C, Chronic; Hepatitis E; Hepatitis, Viral, Human; Humans; Male; Meat; Middle Aged; Raw Foods; Republic of Korea; Retrospective Studies; Treatment Outcome
PubMed: 29145204
DOI: 10.1159/000480506 -
BMC Infectious Diseases Feb 2019Egypt ranks fifth for the burden of viral hepatitis worldwide. As part of Egypt's renewed national strategy for the elimination of viral hepatitis, surveillance for... (Comparative Study)
Comparative Study
Evidence of sustained reductions in the relative risk of acute hepatitis B and C virus infections, and the increasing burden of hepatitis a virus infection in Egypt: comparison of sentinel acute viral hepatitis surveillance results, 2001-17.
BACKGROUND
Egypt ranks fifth for the burden of viral hepatitis worldwide. As part of Egypt's renewed national strategy for the elimination of viral hepatitis, surveillance for acute viral hepatitis (AVH) was re-established during 2014-2017 to describe the current epidemiology and associated risk factors, and changes from surveillance conducted during 2001-2004.
METHODS
Patients with suspected AVH were enrolled, completed a questionnaire, and provided blood for testing for hepatitis viruses A (HAV), B (HBV), C (HCV), D, and E (HEV) infections by enzyme-linked immunosorbent assay. Odds ratios and Chi were used to detect differences between hepatitis types by patient characteristics and exposures. Newcombe-Wilson method was used to compare results between surveillance periods 2001-2004 and 2014-2017.
RESULTS
Between 2014 and 2017, among 9321 patients enrolled, 8362 (89.7%) had one or more markers of AVH including 7806 (93.4%) HAV, 252 (3.0%) HCV, 238 (2.8%) HBV, and 31 (0.4%) HEV infection. HAV infection occurred most commonly among children < 16 years age, while HBV infection occurred among ages 16-35 years and HCV infection in ages greater than 45 years. Healthcare-associated exposures were significantly associated with HBV and HCV infections compared to HAV infection including receiving therapeutic injections, surgery, wound suture, or urinary catheter and IV line insertions, while significant lifestyle exposures included exposure to blood outside the healthcare system, IV drug use, or incarceration. Exposures significantly associated with HAV infection were attending nursery or pre-school, contact with person attending nursery or pre-school, having meals outside the home, or contact with HAV case. Compared with AVH surveillance during 2001-2004, there was a significant increase in the proportion of HAV infections from 40.2 to 89.7% (RR = 2.3) with corresponding reductions in the proportions of HBV and HCV infections from 30.0 to 2.8% (RR = 0.1) and 29.8 to 3.0% (RR = 0.1), respectively.
CONCLUSIONS
Healthcare-associated exposures were significantly association with and remain the greatest risk for HBV and HCV infections in Egypt. Additional studies to evaluate factors associated with the reductions in HBV and HCV infections, and cost effectiveness of routine HAV immunization might help Egypt guide and evaluate control measures.
Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Egypt; Female; Hepatitis A; Hepatitis B; Hepatitis C; Hepatitis, Viral, Human; Humans; Infant; Infection Control; Male; Middle Aged; Risk; Risk Factors; Risk Reduction Behavior; Sentinel Surveillance; Young Adult
PubMed: 30764780
DOI: 10.1186/s12879-019-3806-9