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The article discusses the use of Ribavirin for chronic hepatitis prevention among patients with hematologic malignancies. Topics include Ribavirin monotherapy for infected immunocompromised patients, diagnosis of Hepatitis E (HEV) infection, summary of the outcomes of HEV infection and hematologic malignancies, and solid organ transplant (SOT) patients showing high response rate to ribavirin treatment.

Twenty-four solid-organ-transplant recipients with chronic hepatitis E virus (HEV) infections were given ribavirin therapy for 3 months. All the patients with protracted fecal HEV shedding during treatment suffered a relapse. Monitoring HEV fecal excretion could be used to determine the optimal duration of ribavirin therapy. [ABSTRACT FROM PUBLISHER]

Hepatitis E virus (HEV) has been detected in rabbits, but whether rabbit HEV strains can be transmitted to humans is not known. Of 919 HEV-infected patients in France during 2015-2016, five were infected with a rabbit HEV strain. None of the patients had direct contact with rabbits, suggesting foodborne or waterborne infections. [ABSTRACT FROM AUTHOR]

We screened plasma samples (minipools of 96 samples, corresponding to 53,234 blood donations) from France that had been processed with solvent-detergent for hepatitis E virus RNA. The detection rate was 1 HEV-positive sample/2,218 blood donations. Most samples (22/24) from viremic donors were negative for IgG and IgM against HEV. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hepatitis E virus (HEV) infections are a major cause of acute hepatitis in developing and industrialized countries. Little is known about anti-HEV immunity in solid-organ recipients. METHODS: We screened 263 solid-organ recipients for anti-HEV immunoglobulin G (IgG) at transplantation. They were followed up for 1 year and tested for HEV RNA and anti-HEV antibodies 1 year after transplantation and if their liver enzyme activities increased. RESULTS: A total of 38.4% had anti-HEV IgG at transplantation. The mean concentrations (±SD) of anti-HEV IgG at transplantation (8 ± 17.5 U/mL) and 1 year later (6.4 ± 12.0 U/mL, P = .4) were similar. There were 3 de novo HEV infections during the 1-year follow-up among patients who were HEV seronegative before transplantation, giving an annual incidence of 2.1%. We also identified 3 HEV reinfections among patients who were seropositive before transplantation through detection of HEV RNA, for an annual incidence of 3.3%. Their anti-HEV IgG concentrations were 0.3, 2.1, and 6.2 World Health Organization (WHO) units/mL before transplantation. Reinfection of the patient with the lowest IgG concentration at transplantation had evolved to a chronic infection. CONCLUSIONS: Low anti-HEV antibodies (<7 WHO units/mL) seemed not to protect solid-organ recipients. HEV reinfection in immunocompromised patients can lead to chronic infection, as in primary infections. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) can chronically infect immunocompromised patients. The polyproline region (PPR) and the macro domain of ORF1 protein may modulate virus production and/or the host immune response. We investigated the association between the genetic heterogeneity of HEV quasispecies in ORF1 and the outcome of infection in solid-organ transplant patients. Both sequence entropy and genetic distances during the hepatitis E acute phase were higher in patients whose infection became chronic than in those who cleared the virus. Hence, great quasispecies heterogeneity in the regions encoding the PPR and the macro domain may facilitate HEV persistence. [ABSTRACT FROM AUTHOR]

We explored the performance of a whole blood interferon gamma release assay (IGRA) based on the stimulation of SARS-Cov2-specific T cells by purified recombinant proteins. Twenty volunteers vaccinated with BNT162b2 were selected first for T cell response evaluation using an in-house IGRA, a commercial IGRA, and ELISpot showing a S2 > S1 poly-epitopic response. Next, 64 vaccinated and 103 non-vaccinated individuals were tested for humoral and T cell response (IGRA-Spike/−nucleocapsid recombinant proteins). Following the second vaccine injection, humoral (100%) and IGRA-Spike T cell (95.3%) responses took place irrespective of sex, age, and vaccine type. The humoral response declined first, followed by IGRA-Spike T cell response after the second vaccine injection. Altogether, this study confirms the utility of the IGRA-Spike/−nucleocapsid assay to complement serology in COVID19 vaccinated individuals and those who have recovered from SARS-Cov2. • Whole blood IGRA using recombinant proteins can be used as a surrogate to ELISpot. • COVID19 vaccine Spike T cell response is poly-epitopic (S2 > S1). • Spike T cell response declines after the humoral response. • Nucleocapsid T cell response supports a previous SARS-Cov2 infection. [ABSTRACT FROM AUTHOR]

Background and Aims: Hepatic stellate cells, the major producers of extracellular matrix in the liver, and hepatocytes bear CXCR4 and CCR5, the two main co-receptors for entry of the human immunodeficiency virus (HIV). In vitro studies suggest that HIV-envelope proteins can modulate the replication of hepatitis C virus (HCV) and fibrogenesis. We investigated the influence of HIV tropism on liver fibrosis and the concentration of HCV RNA in HIV--HCV co-infected patients. Methods: We used a phenotypic assay to assess HIV tropism in 172 HCV--HIV co-infected patients: one group (75 patients) had mild fibrosis (score ≤F2) and the other (97 patients) had severe fibrosis (score >F2). We also assessed the relationship between HIV tropism and HCV RNA concentration in all these patients. We also followed 34 of these patients for 3 years to determine the evolution of HIV tropism and liver fibrosis, estimated by liver stiffness. Results: Initially, most patients (91.8%) received a potent antiretroviral therapy. CXCR4-using viruses were found in 29% of patients. The only factor associated with a CXCR4-using virus infection in multivariate analysis was the nadir of CD4 cells: <200/mm³ (OR: 3.94, 95%CI: 1.39-11.14). The median HCV RNA concentrations in patients infected with R5 viruses, those with dual-mixed viruses and those with X4 viruses, were all similar. The prevalence of CXCR4-using viruses in patients with mild fibrosis (≤F2) (31%) and those with severe fibrosis (F3--F4) (28%, p = 0.6) was similar. Longitudinal analyses showed that the presence of CXCR4-using viruses did not increase the likelihood of fibrosis progression, evaluated by measuring liver stiffness. Conclusions: The presence of CXCR4-using viruses in patients receiving a potent antiretroviral therapy does not influence HCV RNA concentration or liver fibrosis. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) strains from rabbits indicate that these mammals may be a reservoir for HEVs that cause infection in humans. To determine HEV prevalence in rabbits and the strains' genetic characteristics, we tested bile, liver, and additional samples from farmed and wild rabbits in France. We detected HEV RNA in 7% (14/200) of bile samples from farmed rabbits (in 2009) and in 23% (47/205) of liver samples from wild rabbits (in 2007-2010). Full-length genomic sequences indicated that all rabbit strains belonged to the same clade (nucleotide sequences 72.2%-78.2% identical to HEV genotypes 1-4). Comparison with HEV sequences of human strains and reference sequences identified a human strain closely related to rabbit strain HEV. We found a 93-nt insertion in the X domain of open reading frame 1 of the human strain and all rabbit HEV strains. These findings indicate that the host range of HEV in Europe is expanding and that zoonotic transmission of HEV from rabbits is possible. [ABSTRACT FROM AUTHOR]

Using a validated sensitive assay, we found hepatitis E virus (HEV) IgG in 52.5% of voluntary blood donors in southwestern France. This finding suggests HEV is highly endemic to this region. The high HEV prevalence may reflect local dietary practices, such as eating uncooked pork and game products. [ABSTRACT FROM AUTHOR]

We screened 735 HIV-infected patients in Switzerland with unexplained alanine aminotransferase elevation for hepatitis E virus (HEV) immunoglobulin G. Although HEV seroprevalence in this population is low (2.6%), HEV RNA can persist in patients with low CD4 cell counts. Findings suggest chronic HEV infection should be considered as a cause of persistent alanine aminotransferase elevation. [ABSTRACT FROM AUTHOR]

Infections with hepatitis E virus (HEV) in solid-organ transplant recipients can lead to chronic hepatitis. However, the incidence of de novo HEV infections after transplantation and risk for reactivation in patients with antibodies against HEV before transplantation are unknown. Pretransplant prevalence of these antibodies in 700 solid-organ transplant recipients at Toulouse University Hospital in France was 14.1%. We found no HEV reactivation among patients with antibodies against HEV at the first annual checkup or by measuring liver enzyme activities and HEV RNA. In contrast, we found 34 locally acquired HEV infections among patients with no antibodies against HEV, 47% of whom had a chronic infection, resulting in an incidence of 3.2/100 person-years. Independent risk factors for HEV infection were an age <52 years at transplantation and receiving a liver transplant. Effective prophylactic measures that include those for potential zoonotic infections should reduce the risk for HEV transmission in this population. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatitis E virus (HEV) infection can evolve to chronic hepatitis in immunocompromised patients. Pegylated α-interferon can effectively treat chronic HEV infection after liver transplantation but is contraindicated for kidney transplantation. We assessed the antiviral effect of ribavirin monotherapy in patients with chronic HEV infection following kidney transplantation. Methods: In a pilot study performed at Toulouse University Hospital, 6 patients that received kidney transplants who were positive for HEV RNA (infected with HEV for 36.5 months; [range, 11–46 months]) were given ribavirin monotherapy for 3 months. Ribavirin was given at 600–800 mg/day in 2 separate doses, based on the patient''s ability to clear creatinine. Results: Median serum concentration of HEV RNA at baseline was 5.77 log copies/mL (range, 4.35–7.35 log copies/mL). Three months after ribavirin therapy commenced, HEV RNA was undetectable in serum samples from all patients. A sustained virologic response was observed in 4 patients; the other 2 patients relapsed at 1 and 2 months after ribavirin therapy ended. At the end of the study, all patients had normal levels of alanine and aspartate aminotransferase. Anemia was the main side effect caused by ribavirin therapy. Conclusions: Ribavirin monotherapy inhibits the replication of HEV in vivo and might induce a sustained virological response in patients with chronic HEV infections. Further studies are required to determine the optimal duration of ribavirin therapy. [Copyright &y& Elsevier]

Background. Hepatitis E virus (HEV) infections can lead to chronic hepatitis in immunocompromised patients. We have investigated the risk factors for HEV infection among solid-organ transplant recipients and the characteristics of these infections. Methods. We performed serological tests, quantified the virus, and genotyped the virus in plasma samples. We performed a case-control study with HEV-infected patients and control participants matched for sex and age who were recruited from a population of solid-organ transplant recipients with no markers of HEV infection. Results. We investigated 38 consecutive cases of HEV genotype 3 infection. Twenty-two (58%) of these 38 patients developed a chronic infection. The acute-phase aminotransferase levels were higher in the patients who cleared the virus than in those who developed chronic infections. The anti-HEV immunoglobulin G and immunoglobulin M profiles and HEV RNA concentration in patients who cleared the virus were similar to those in patients who developed a chronic infection. A logistic regression analysis of 37 case patients and 148 control participants indicated that the only factor independently associated with HEV infection was the consumption of game meat (68% of case patients vs 47% of control participants; odds ratio, 2.32; 95% confidence interval, 1.04-5.15). Conclusion. Immunocompromised patients should avoid eating insufficiently cooked game meat or pork products so as to reduce the risk of HEV infection and chronic liver disease. [ABSTRACT FROM AUTHOR]

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Studies comparing SARS-CoV-2 nasopharyngeal (NP) viral load (VL) according to virus variant and host vaccination status have yielded inconsistent results. We conducted a single center prospective study between July and September 2021 at the drive-through testing center of the Toulouse University Hospital. We compared the NP VL of 3775 patients infected by the Delta (n = 3637) and Alpha (n = 138) variants, respectively. Patient's symptoms and vaccination status (2619 unvaccinated, 636 one dose and 520 two doses) were recorded. SARS-CoV-2 RNA testing and variant screening were assessed by using Thermo Fisher® TaqPath™ COVID-19 and ID solutions® ID™ SARS-CoV-2/VOC evolution Pentaplex assays. Delta SARS-CoV-2 infections were associated with higher VL than Alpha (coef = 0.68; p ≤ 0.01) independently of patient's vaccination status, symptoms, age and sex. This difference was higher for patients diagnosed late after symptom onset (coef = 0.88; p = 0.01) than for those diagnosed early (coef = 0.43; p = 0.03). Infections in vaccinated patients were associated with lower VL (coef = −0.18; p ≤ 0.01) independently of virus variant, symptom, age and sex. Our results suggest that Delta infections could lead to higher VL and for a longer period compared to Alpha infections. By effectively reducing the NP VL, vaccination could allow for limiting viral spread, even with the Delta variant. [ABSTRACT FROM AUTHOR]

Abstract: Background: Due to their high prevalence, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections need accurate and rapid diagnosis tools. Objectives: Technical performances of the UniCel DxI 800 analyser (Beckman Coulter) and a comparison with the Vitros ECi (Ortho Clinical Diagnostics) were performed for five serological markers: HBsAg, total anti-HBc, anti-HBc IgM, anti-HBs and anti-HCV. Study design: Reproducibility was determined by repeated tests on the manufacturers’ controls. The performance of the UniCel DxI 800 was assessed by testing negative and positive samples previously analysed with the Vitros ECi. The accuracy and linearity of anti-HBs assay were evaluated using the WHO international standard (W1042). Results: The intra-assay and inter-assay coefficients of variation were: 0.8% and 4.4% for HBsAg, 2.4% and 6.2% for anti-HBc, 5% and 8.7% for anti-HBc IgM, 2.1% and 5.1% for anti-HBs and 3.7% and 7.4% for anti-HCV. The two methods were concordant: 100% agreement for the five markers except for the negative HBsAg sera (99%). The anti-HBs results correlated well with the Vitros ECi (r =0.925 with p <0.0001) and the WHO standard (r 2 =0.9996). Throughput was 216tests/h. Conclusion: The high throughput, specificity and sensitivity make UniCel DxI 800 assays useful for routine diagnoses of HCV and HBV infections. [Copyright &y& Elsevier]

We characterized 42 hepatitis E virus (HEV) genotype 3 strains from infected patients in France in 3 parts of the genome and sequenced the full-length HEV genotype 3f genome found in Europe. These strains are closely related to swine strains in Europe, which suggests zoonotic transmission of HEV in France. [ABSTRACT FROM AUTHOR]

Background. Hepatitis C virus (HCV) genotype is an important determinant of virological response to antiviral therapies. Currently, there are no data available on the molecular epidemiology and interferon susceptibility of the natural intergenotypic recombinant RF1_2k/1b (RF1) strain. Methods. Genotyping and RF1-PCR screening were performed on samples from 604HCVRNA--positive individuals from 7 countries. uPA/SCID mice carrying human hepatocytes (chimeric mice) were infected with the RF1_2k/1b strain, and the susceptibility of the strain to interferon and ribavirin was compared with the susceptibilities of 2 different strains of genotype B, used as references. Results. Six new RF1 cases were identified in this study; 5 (2%) of 281 in Russia and 1 (1%) of 90 in Uzbekistan. Phylogenetic analyses based on Core/E1 and NS5b indicated that all RF1 representatives share a common evolutionary ancestor. Infection with RF1 was established in chimeric mice. Reduction of RF1 viral load was observed in response to 3 injections of 3 μg/kg pegylated-interferon alpha-2a alone or in combination with 50 mg/kg of ribavirin (0.5 or 1.4 log-copies/mL). Conclusions. All identified RF1-type strains appear to be introduced from a single source, suggesting that intergenotypic recombination in HCV is sporadic and not associated with cocirculation of different genotypes in a population. The RF1 strain in this study was responsive to interferon in vivo. [ABSTRACT FROM AUTHOR]

HLA-G is a non-classical HLA class Ib molecule primarily expressed in trophoblast cells, and is thought to play a key role in the induction of materno-fetal tolerance during pregnancy. In addition, theHLA-Ggene provides a suitable leader sequence peptide capable of binding to HLA-E. However, the existence of placentas homozygous for theHLA-G*0105Nnull allele suggests that HLA-G1 might not be essential for fetal survival. To investigate whether expression of theHLA-G*0105Nallele supports HLA-E cell surface expression, we transfected theHLA-G*0105Ngene into JAR trophoblast cells. Flow cytometry analysis showed thatHLA-G*0105N-transfected cells express surface HLA-E to a similar extent as the unmutatedHLA-Ggene, whereas HLA-G1 cell surface expression was undetectable. Using the NKL cell line in a standard51Cr release assay, the HLA-E molecules were found to inhibit natural killer lysis, through a mechanism partially dependent on CD94/NKG2A-mediated recognition. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the first cause of viral hepatitis in the world. While the water-borne HEV genotypes 1 and 2 are found in developing countries, HEV genotypes 3 and 4 are endemic in developed countries due to the existence of animal reservoirs, especially swine. An HEV infection produces many extra-hepatic manifestations in addition to liver symptoms, especially neurological disorders. The most common are neuralgic amyotrophy or Parsonage–Turner syndrome, Guillain–Barré syndrome, myelitis, and encephalitis. The pathophysiology of the neurological injuries due to HEV remains uncertain. The immune response to the virus probably plays a role, but direct virus neurotropism could also contribute to the pathophysiology. This review describes the main neurological manifestations and their possible pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) infection can lead to a variety of neurological disorders. While HEV RNA is known to be present in the central nervous system, HEV quasispecies in serum and cerebrospinal fluid (CSF) have rarely been explored. We studied the virus' quasispecies in the blood and the CSF of five patients at the onset of their neurological symptoms. The samples of three patients suffering from meningitis, neuralgic amyotrophy and acute inflammatory polyradiculoneuropathy were taken at the acute phase of the HEV infection. The samples from the other two patients were taken during the chronic phase (5 years after HEV diagnosis) when they presented with clinical signs of encephalitis. We sequenced at least 20 randomly polyproline regions of the selected virus clones. Phylogenetic analysis of the virus variants in the blood and the CSF revealed no virus compartmentalization for the three acute-phase patients but there was clear evidence of HEV quasispecies compartmentalization in the CSF of the two patients during chronic infection. In conclusion, prolonged infection in the immunocompromised condition can lead to independent virus replication in the liver and the tissues, producing viruses in CSF. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the most prevalent hepatitis virus worldwide. Genotypes 3 (HEV3) and 4 (HEV4) as well as rat HEV can lead to chronic hepatitis E and cirrhosis in immunosuppressed patients. Within the last decade, several options for treating chronic hepatitis have been developed and have achieved a sustained virological response. However, there are still unmet needs such as optimizing immunosuppression to allow HEV clearance with or without ribavirin, as well as alternative therapies to ribavirin that are discussed in this paper. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a leading cause of viral hepatitis in the world. It is usually responsible for acute hepatitis, but can lead to a chronic infection in immunocompromised patients. The host's innate immune response is the first line of defense against a virus infection; there is growing evidence that HEV RNA is recognized by toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), leading to interferon (IFN) production. The IFNs activate interferon-stimulated genes (ISGs) to limit HEV replication and spread. HEV has developed strategies to counteract this antiviral response, by limiting IFN induction and signaling. This review summarizes the advances in our knowledge of intracellular pathogen recognition, interferon and inflammatory response, and the role of virus protein in immune evasion. [ABSTRACT FROM AUTHOR]

Quantification of HBV DNA is used for initiating and monitoring antiviral treatment. We have evaluated the Xpert HBV Viral Load (VL) assay on the GeneXpert instrument. We estimated its limit of detection to be 7.5 IU/mL. Reproducibility was 1.1–12.7% as assessed by the coefficients of variation for 3 different samples. The assay was linear from 2 to 8 log 10 IU/mL for HBV genotypes A to F. Its clinical performance was evaluated by testing prospectively 100 HBV DNA-positive samples with the Xpert HBV VL and Aptima Quant HBV assays. The results from the 2 assays were correlated, with a modest bias (−0.10 log 10 IU/mL) between them by Bland–Altman analysis. Patient monitoring with 80 samples performed with both assays gave similar patient profiles with trends in the same direction. The Xpert HBV Viral load assay is reliable enough for quantifying HBV DNA in clinical practice. [ABSTRACT FROM AUTHOR]

Unfortunately, the supplement tables are missing in the original article. The missing files have been included here. [ABSTRACT FROM AUTHOR]