Fulminant Adenoviral-Induced Hepatitis in Immunosuppressed Patients
Ontology highlight
ABSTRACT:
SUBMITTER: Kager J
PROVIDER: S-EPMC9323657 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The goal of this experiment was to investigate the early mechanisms of human fulminant hepatitis through ConA-induced hepatitis model.Early diagnosis and interventions are important for patients with fulminant hepatitis and gene expression may be pivotal in the early diagnosis. Keyword :ConA-induced hepatitis model
2009-07-21 | GSE17184 | GEO
Project description:The goal of this experiment was to investigate the early mechanisms of human fulminant hepatitis through ConA-induced hepatitis model.Early diagnosis and interventions are important for patients with fulminant hepatitis and gene expression may be pivotal in the early diagnosis. Keyword :ConA-induced hepatitis model ConA was injected through the mouse caudal vein at one of 4 time points (0 hr, 1 hr, 3 hr, 6 hr). The effects of ConA treatment on hepatic gene expression at these time points were analyzed .There are 3 replicates at each timepoint then 4*3=12 samples in all.
2009-07-21 | E-GEOD-17184 | biostudies-arrayexpress
Project description:Fulminant hepatitis is a severe clinical disease characterized by a marked decline in liver function and encephalopathy. In a previous survey, using metagenomics in a group of 27 patients with this clinical condition, we observed an expressive quantity of reads of the Human pegivirus-1 (HPgV-1). Therefore, the objective of this study was to evaluate the frequency, molecular features, and HPgV-1 circulating genotypes in patients with fulminant hepatitis. After testing the collected plasma samples, we discovered twelve samples (44.4%) that were positive for HPgV-1 RNA (using both real-time and nested PCR). The positive samples presented a mean cycle threshold (Ct) of 28.5 (±7.3). Genotyping assignments revealed that all HPgV-1 positive samples belonged to the HPgV-1 genotype 2 (both subgenotypes 2A and 2B were identified). Although HPgV-1 is considered a commensal virus, little is known regarding its prevalence and genotypes in cases of fulminant hepatitis. More research is needed to understand whether HPgV-1 can be implicated in clinical disorders and infectious diseases.
| S-EPMC10536510 | biostudies-literature
Project description:Fulminant hepatitis (FH) is a life-threatening liver disease characterised by intense immune attack and massive liver cell death. The common precore stop codon mutation of hepatitis B virus (HBV), A1896, is frequently associated with FH, but lacks specificity. This study attempts to uncover all possible viral nucleotides that are specifically associated with FH through a compiled sequence analysis of FH and non-FH cases from acute infection. We retrieved 67 FH and 280 acute non-FH cases of hepatitis B from GenBank and applied support vector machine (SVM) model to seek candidate nucleotides highly predictive of FH. Six best candidates with top predictive accuracy, 92.5%, were used to build a SVM model; they are C2129 (85.3%), T720 (83.0%), Y2131 (82.4%), T2013 (82.1%), K2048 (82.1%), and A2512 (82.1%). This model gave a high specificity (99.3%), positive predictive value (95.6%), and negative predictive value (92.1%), but only moderate sensitivity (64.2%). We successfully built a SVM model comprising six variants that are highly predictive and specific for FH: four in the core region and one each in the polymerase and the surface regions. These variants indicate that intracellular virion/core retention could play an important role in the progression to FH.
| S-EPMC5749291 | biostudies-literature
Project description:In rare cases, hepatitis A virus (HAV) and hepatitis B virus (HBV) can cause fulminant viral hepatitis (FVH), characterized by massive hepatocyte necrosis and an inflammatory infiltrate. Other viral etiologies of FVH are rarer. FVH is life-threatening, but the patients are typically otherwise healthy, and normally resistant to other microbes. Only a small minority of infected individuals develop FVH, and this is the key issue to be addressed for this disease. In mice, mouse hepatitis virus 3 (MHV3) infection is the main model for dissecting FVH pathogenesis. Susceptibility to MHV3 differs between genetic backgrounds, with high and low mortality in C57BL6 and A/J mice, respectively. FVH pathogenesis in mice is related to uncontrolled inflammation and fibrinogen deposition. In humans, FVH is typically sporadic, but rare familial forms also exist, suggesting that there may be causal monogenic inborn errors. A recent study reported a single-gene inborn error of human immunity underlying FVH. A patient with autosomal recessive complete IL-18BP deficiency was shown to have FVH following HAV infection. The mechanism probably involves enhanced IL-18- and IFN-?-dependent killing of hepatocytes by NK and CD8 T cytotoxic cells. Proof-of-principle that FVH can be genetic is important clinically, for the affected patients and their families, and immunologically, for the study of immunity to viruses in the liver. Moreover, the FVH-causing IL18BP genotype suggests that excessive IL-18 immunity may be a general mechanism underlying FVH, perhaps through the enhancement of IFN-? immunity.
| S-EPMC7153696 | biostudies-literature
Project description:AimTo study host gene expression and number of immune cells in liver tissues from patients with fulminant hepatitis E (FH-E).MethodsMicroarray-based expression profiling was done using Illumina Human WG-6_v3_BeadChip arrays on post-mortem liver tissue from 5 patients with FH-E, and compared with similar tissue from 6 patients with fulminant hepatitis B (FH-B; disease controls) and normal liver tissue from 6 persons. Differential expression was defined as ≥ 2.0-fold change with Benjamini-Hochberg false discovery rate below 0.05 using t-test in liver tissue from FH-B and FH-E, than healthy liver tissue. For some genes that showed differential expression in FH-E, microarray data were validated using quantitative reverse transcription PCR. Differentially expressed gene lists were then subjected to "Gene Ontology" analysis for biological processes, and pathway analysis using BioCarta database on the DAVID server. In addition, tissue sections were stained for CD4(+), CD8(+) and CD56(+) cells using indirect immunohistochemistry; cells staining positive for each of these markers were counted and compared between groups.ResultsCompared to normal livers, those from patients with FH-E and FH-B showed differential expression of 3377 entities (up-regulated 1703, downregulated 1674) and 2572 entities (up 1164, down 1408), respectively. This included 2142 (up 896, down 1246) entities that were common between the two sets; most of these belonged to metabolic, hemostatic and complement pathways, which are active in normal livers. Gene expression data from livers of patients with FH-E but not those of FH-B showed activation of several immune response pathways, particularly those involving cytotoxic T cells. The fold-change values of mRNA for selected genes in livers from FH-E than in normal liver tissue determined using quantitative reverse transcription PCR showed excellent concordance with microarray analysis. At immunohistochemistry, CD8(+) T cells showed an increase in liver biopsies from both FH-E [median 53.4 per arbitrary unit area (range 31.2-99.9)] and FH-B [median 49.3 (19.3-51.0); P = 0.005] compared to control liver tissue [median 6.9 (3.1-14.9)].ConclusionFH-E patients show CD8(+) T cell infiltration and increased gene expression of cytotoxic T cell pathways in liver, suggesting a possible pathogenetic role for these cells.
| S-EPMC4499345 | biostudies-literature
Project description:BACKGROUND & AIMS:Fulminant hepatitis is a rare outcome of infection with hepatitis E virus. Several recent reports suggest that virus variation is an important determinant of disease progression. To critically examine the evidence that virus-specific factors underlie the development of fulminant hepatitis following hepatitis E virus infection. METHODS:Published sequence information of hepatitis E virus isolates from patients with and without fulminant hepatitis was collected and analysed using statistical tests to identify associations between virus polymorphisms and disease outcome. RESULTS:Fulminant hepatitis has been reported following infection with all four hepatitis E virus genotypes that infect humans comprising multiple phylogenetic lineages within genotypes 1, 3 and 4. Analysis of virus sequences from individuals infected by a common source did not detect any common substitutions associated with progression to fulminant hepatitis. Re-analysis of previously reported associations between virus substitutions and fulminant hepatitis suggests that these were probably the result of sampling biases. CONCLUSIONS:Host-specific factors rather than virus genotype, variants or specific substitutions appear to be responsible for the development of fulminant hepatitis.
| S-EPMC4676335 | biostudies-literature
Project description:Infections of immunocompromised patients with human adenoviruses (hAd) can develop into life-threatening conditions, whereas drugs with anti-adenoviral efficiency are not clinically approved and have limited efficacy. Small double-stranded RNAs that induce RNAi represent a new class of promising anti-adenoviral therapeutics. However, as yet, their efficiency to treat hAd5 infections has only been investigated in vitro. In this study, we analyzed artificial microRNAs (amiRs) delivered by self-complementary adeno-associated virus (scAAV) vectors for treatment of hAd5 infections in immunosuppressed Syrian hamsters. In vitro evaluation of amiRs targeting the E1A, pTP, IVa2, and hexon genes of hAd5 revealed that two scAAV vectors containing three copies of amiR-pTP and three copies of amiR-E1A, or six copies of amiR-pTP, efficiently inhibited hAd5 replication and improved the viability of hAd5-infected cells. Prophylactic application of amiR-pTP/amiR-E1A- and amiR-pTP-expressing scAAV9 vectors, respectively, to immunosuppressed Syrian hamsters resulted in the reduction of hAd5 levels in the liver of up to two orders of magnitude and in reduction of liver damage. Concomitant application of the vectors also resulted in a decrease of hepatic hAd5 infection. No side effects were observed. These data demonstrate anti-adenoviral RNAi as a promising new approach to combat hAd5 infection.
| S-EPMC5537171 | biostudies-literature
Project description:RNA interference has demonstrated its potential as an antiviral therapy for treatment of human adenovirus (hAd) infections. The only existing viral vector-based system for delivery of anti-adenoviral artificial microRNAs available for in vivo use, however, has proven to be inefficient in therapeutic applications. In this study, we investigated the potential of stabilized small interfering RNA (siRNA) encapsulated in lipid nanoparticles (LNPs) for treatment of hepatic hAd serotype 5 (hAd5) infection in an hAd infection model using immunosuppressed Syrian hamsters. The siRNA sipTPmod directed against the adenoviral pre-terminal protein (pTP) and containing 2'-O-methyl modifications as well as phosphorothioate linkages effectively inhibited hAd5 infection in vitro. In light of this success, sipTPmod was encapsulated in LNPs containing the cationic lipid XL-10, which enables hepatocyte-specific siRNA transfer, and injected intravenously into hAd5-infected immunosuppressed Syrian hamsters. This resulted in a significant reduction of liver hAd5 titers, a trend toward reduced liver injury and inflammation, and reduction of viral titers in the blood and spleen compared with hAd5-infected animals that received a non-silencing siRNA. These effects were demonstrated in animals infected with low and moderate doses of hAd5. These data demonstrate that hepatic hAd5 infection can be successfully treated with anti-adenoviral sipTPmod encapsulated in LNPs.
| S-EPMC10280093 | biostudies-literature
Project description:Hepatitis of undetermined origin can be caused by a wide variety of pathogens, sometimes emerging pathogens. We report the discovery, by means of routine shotgun metagenomics, of a new virus belonging to the family Circoviridae, genus Circovirus, in a patient in France who had acute hepatitis of unknown origin.
| S-EPMC10124635 | biostudies-literature