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Objectives: Human herpesvirus-8 (HHV-8) can cause Kaposi's sarcoma or B lymphoproliferative disorders such as multicentric Castleman disease. Patient follow-up is based on assessing the HHV-8 viral load, which is usually achieved using real-time polymerase chain reaction (PCR). The HHV-8 Premix r-gene kit (BioMérieux) was used by some laboratories in the past, but BioMérieux ceased the production and distribution of this kit in 2021-2022. Other kits need to be tested so that they can be used for diagnostic purposes. Here we evaluated two commercial kits: HHV8 ELITe MGB Kit (ELITech) and Quanty HHV-8 (Clonit) and compared them with the HHV-8 Premix r-gene kit. Methods: We used whole blood samples that had previously been tested with the HHV-8 Premix r-gene kit for diagnostic purposes. Overall, 46 samples (37 HHV-8-positive and 9 HHV-8-negative) were tested with the ELITe MGB Kit and 37 (29 HHV-8-positive and 8 HHV-8-negative) with the Quanty HHV-8 kit. The different methods were compared using Bland-Altman and Passing-Bablok tests with Analyse-it software. Results: Qualitative results were concordant except for one HHV-8 low-positive sample that was found to be negative by the ELITe MGB Kit. The quantitative results were also concordant; both kits showed mean differences of 0.58 log10 copies/ml and 0.73 log10 copies/ml, respectively, compared to the Premix r-gene kit. Conclusions: Both the methods tested produced acceptable results and could be used for diagnostic purposes. It should be remembered that there is no international standard for HHV-8 quantification and that patients should always be followed using the same method.
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A 14-year-old patient underwent liver transplant. Three months after transplantation, EBV associated lymphoma was suspected. EBV serologies before and after transplantation were particularly discrepant. Eighteen months before transplantation, the serological profile suggested a recent EBV primary-infection, four months before transplantation, we had isolated anti-EBNA IgG and five days after transplantation, the serological profile suggested a past infection. All EBV PCR performed on whole blood were negative. Retrospectively, immunoblots anti-EBV IgG were performed. Blots showed no anti-EBV IgG before and until the day of liver transplantation. Five days after transplantation, slight bands of both IgG anti-p18 (VCA) and anti-EBNA-1 were found, without any other serological marker. These were probably due to passive transfers of IgG during surgery. There was therefore no argument for an immunization against EBV before or after liver transplant for this patient.
Un patient de 14 ans a subi une transplantation hépatique. Trois mois après la transplantation, un lymphome associé à l'EBV a été suspecté. Les sérologies anti-EBV (IgG anti-VCA et anti-EBNA, IgM anti-VCA) montraient des résultats particulièrement discordants et ininterprétables : profil de primo-infection EBV récente 18 mois avant la greffe, IgG anti-EBNA isolées 4 mois avant la greffe et profil d'infection ancienne 5 jours après la greffe. Les PCR EBV réalisées sur sang total étaient toujours indétectables. Rétrospectivement, des immunoblots IgG anti-EBV ont été réalisés. Les blots ne montraient pas d'IgG anti-EBV en pré-greffe jusqu'au jour de la transplantation. Cinq jours après la greffe, le blot montrait la présence d'anti-p18 (VCA) et anti-EBNA-1 présents sous forme de traces, sans autre marqueur sérologique d'infection EBV, très probablement dues à des transferts passifs d'anticorps pendant la transplantation. Aucun argument sérologique ni moléculaire n'a été retenu pour une immunisation anti-EBV avant ou après la transplantation hépatique pour ce patient.
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Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Adolescente , Anticorpos Antivirais , Antígenos Virais , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Humanos , Imunoglobulina G , Imunoglobulina M , Estudos RetrospectivosRESUMO
We report a transfusion-transmitted hepatitis A virus infection in an immunocompromised patient in France, detected shortly after a transfusion of pathogen-reduced pooled platelets. This case raises questions about the efficacy of donor screening methods. Additional safety measures, such as routine donation screening, should be considered.
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Vírus da Hepatite A , Torque teno virus , Doadores de Sangue , Transfusão de Sangue , Vírus da Hepatite A/genética , Humanos , Hospedeiro Imunocomprometido , Programas de RastreamentoRESUMO
OBJECTIVE: Antibody response to the messenger RNA (mRNA) COVID-19 vaccine has been shown to be diminished in rituximab (RTX)-treated patients. We undertook this study to compare humoral and T cell responses between healthy controls, patients with autoimmune diseases treated with RTX, and those treated with other immunosuppressants, all of whom had been vaccinated with 2 doses of the mRNA COVID-19 vaccine. METHODS: We performed anti-spike IgG and neutralization assays just before and 28 days after the second BNT162b2 (Pfizer-BioNTech) vaccine dose. The specific T cell response was assessed in activated CD4 and CD8 T cells using intracellular flow cytometry staining of cytokines (interferon-γ, tumor necrosis factor, and interleukin-2) after stimulation with SARS-CoV-2 spike peptide pools. RESULTS: A lower proportion of responders with neutralizing antibodies to the vaccine was observed in the RTX group (29%; n = 24) compared to the other immunosuppressants group (80%; n = 35) (P = 0.0001) and the healthy control group (92%; n = 26) (P < 0.0001). No patients treated with RTX in the last 6 months showed a response. Time since last infusion was the main factor influencing humoral response in RTX-treated patients. The functional CD4 and CD8 cellular responses to SARS-CoV-2 peptides for each single cytokine or polyfunctionality were not different in the RTX group compared to the other immunosuppressants group or the control group. In RTX-treated patients, the T cell response was not different between patients with and those without a humoral response. CONCLUSION: RTX induced a diminished antibody response to the mRNA COVID-19 vaccine, but the functional T cell response was not altered compared to healthy controls and autoimmune disease patients treated with other immunosuppressants. Further work is needed to assess the clinical protection granted by a functionally active T cell response in the absence of an anti-spike antibody response.
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Anticorpos Antivirais/imunologia , Doenças Autoimunes , Vacina BNT162/imunologia , Vacinas contra COVID-19/imunologia , COVID-19 , Doenças Autoimunes/tratamento farmacológico , COVID-19/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , RNA Mensageiro , Rituximab/uso terapêutico , SARS-CoV-2RESUMO
Patients with multiple myeloma are at high risk of severe forms of COVID-19. Despite data showing diminished response to vaccine, the era of highly efficient mRNA vaccine might be a gamechanger. We sought to examine response to mRNA vaccine between healthy controls (n = 28) and multiple myeloma (MM) patients (n = 27). Response was analyzed 1 month after the second dose of anti-SARS-CoV-2 BNT162b2 vaccine. Multiple myeloma patients showed diminished levels of Anti-Spike IgG levels compared to controls, but with a high proportion of patients achieving a humoral response (89% vs. 97% in controls). Neutralizing antibodies were present in 74% of patients versus 96% of controls. Patients under current daratumumab treatment had neutralizing activity of anti-SARS-CoV-2 antibodies. Multiple myeloma patients show diminished response to SARS-COV-2 vaccine but with still high response rate. The main potential risk factor of non-response to COVID-19 vaccine was uncontrolled disease under treatment.
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COVID-19 , Mieloma Múltiplo , Vacina BNT162 , Vacinas contra COVID-19 , Humanos , RNA Mensageiro/genética , SARS-CoV-2 , VacinaçãoRESUMO
BACKGROUND: The objectives were to characterize Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) in patients with acute kidney injury (AKI). METHODS: Kidney biopsy samples in two Caucasian patients and one African with COVID-19 AKI were investigated. RESULTS: All patients had a high-level non-selective glomerular proteinuria. SARS-CoV-2 samples by real-time polymerase chain reaction (RT- PCR) assay were all-negative, as well as for virus particles in the kidney by electron microscopy. The three patients and patients with other AKI did not differ significantly with regard to angiotensin-converting enzyme 2 and transmembrane protease serine 2 kidney staining. CONCLUSIONS: The kidney damage particularly in Caucasians in COVID-19 seems to be an AKI, possibly by the systemic inflammatory response.
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There is growing concern regarding the risk of transfusion- transmitted (TT) hepatitis E. Since the first described case in 2006, several TT hepatitis E have been reported to the French hemovigilance network. We performed a retrospective analysis of all cases of TT hepatitis E reported between 2006 and 2016. Transfusion-transmitted hepatitis E with high imputability according to phylogenetic analysis occurred in 23 patients aged 8 to 88 years and involved mostly solid organ recipients (nâ¯=â¯9) or patients with malignant hematological diseases (nâ¯=â¯9, including 4 hematopoietic allograft recipients). Involved blood products were plasma (nâ¯=â¯7), among which 6 had undergone pathogen reduction with solvent/detergent (nâ¯=â¯4) or amotosalen + ultra-violet A (UVA) (nâ¯=â¯2 from 1 donation) treatments, red blood concentrates (nâ¯=â¯7), apheresis platelets concentrates (nâ¯=â¯3) and whole blood pooled platelets concentrates (nâ¯=â¯6), among which one had underwent amotosalen + UVA treatment. Median hepatitis E virus (HEV) RNA dose infused was 5.79 [4.36-10.10] log IU. HEV infection progressed to chronic hepatitis E in 14 (61%) immunocompromised patients, 2 of whom had advanced liver fibrosis at diagnosis. Chronic hepatitis E patients cleared HEV with ribavirin treatment (nâ¯=â¯10), after immunosuppressive drug reduction (nâ¯=â¯3), or spontaneously (nâ¯=â¯1). One additional organ transplant recipient with associated co-morbidities died with ongoing HEV infection and multiple organ failure. The other 8 (34.8%) patients with TT hepatitis E cleared HEV within 6 months with ribavirin treatment (nâ¯=â¯3), reduced immunosuppression (nâ¯=â¯1) or spontaneously (nâ¯=â¯4). Red cells, platelets, and plasma transfusions may be associated with TT hepatitis E that can evolve to chronic hepatitis E in immunocompromised patients. Hepatitis E virus has emerged in France as a clinically significant TT infection risk.
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Doadores de Sangue/estatística & dados numéricos , Segurança do Sangue/estatística & dados numéricos , Hepatite E/epidemiologia , Reação Transfusional/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Doença Crônica , Feminino , França/epidemiologia , Hepatite E/diagnóstico , Hepatite E/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Reação Transfusional/diagnóstico , Adulto JovemRESUMO
Usually self-limited, hepatitis E virus (HEV) infection may evolve to chronicity and cirrhosis in immunosuppressed patients. HEV infection has been described in solid-organ transplantation and hematology patients, but for allogeneic hematopoietic stem cell transplant (alloHSCT) recipients, only small cohorts are available. This retrospective nationwide multi-center series aimed to describe HEV diagnostic practices in alloHSCT French centers, and the course of infection in the context of alloHSCT. Twenty-nine out of 37 centers participated. HEV search in case of liver function tests (LFT) abnormalities was never performed in 24% of centers, occasionally in 55%, and systematically in 21%. Twenty-five cases of active HEV infection were diagnosed in seven centers, all because of LFT abnormalities, by blood nucleic acid testing. HEV infection was diagnosed in three patients before alloHSCT; HEV infection did not influence transplantation planning, and resolved spontaneously before or after alloHSCT. Twenty-two patients were diagnosed a median of 283 days after alloHSCT. Nine patients (41%) had spontaneous viral clearance, mostly after immunosuppressive treatment decrease. Thirteen patients (59%) received ribavirin, with sustained viral clearance in 11/12 evaluable patients. We observed three HEV recurrences but no HEV-related death or liver failure, nor evolution to cirrhosis.
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Transplante de Células-Tronco Hematopoéticas , Vírus da Hepatite E/isolamento & purificação , Hepatite E/diagnóstico , Adulto , Idoso , Feminino , França/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatite E/epidemiologia , Hepatite E/imunologia , Hepatite E/terapia , Vírus da Hepatite E/imunologia , Humanos , Imunossupressores/efeitos adversos , Fígado/patologia , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Cacicol®, a topical eye biopolymer containing a poly-carboxymethylglucose sulfate solution that is a regenerating matrix therapy agent, intended for wound healing of persistent corneal epithelial defects. Based on the chemical composition, we hypothesized that Cacicol® may compete with natural heparan sulfate (HS) which initiates cell surface attachment of herpes simplex virus type-1 (HSV-1), varicella zoster virus (VZV) and human adenovirus (HAdV), three viruses associated with corneal infections. METHODS: Cacicol® was compared to vehicle in the following viral strains: HSV-1 SC16 strain and HSV-1 PSLR, a clinical isolate highly resistant to acyclovir and foscarnet; VZV ATH and VZV FLO, two VZV clinical isolates; and HAdV-D37 strain. Viruses in Cacicol® or vehicle were added to cells for 1 h during adsorption then viral replication was assessed by plaque reduction assays on Vero cells for HSV-1 and MeWo cells for VZV and by immunostaining assay on Hep-2 cells for HAdV-D37. RESULTS: The vehicle had no effect, dose-dependent effects were demonstrated when HSV-1 SC16, HSV-1 PSLR, VZV ATH and VZV FLO were inoculated in the presence of Cacicol®, inhibiting viral replication by 98.4%, 98.9%, 90.1% and 89.0%, respectively. Cacicol® had no antiviral effect against HAdV-D37. CONCLUSIONS: Cacicol® has a significant antiviral activity on HSV-1 and VZV, but not on HAdV-D37. The lack of effect on HAdV is probably because it is less dependent on HS interactions for cell entry. Clinical studies are necessary to determine Cacicol® for an adjunct or alternative therapy of corneal HSV-1 or VZV infection, particularly for the management of antiviral resistant HSV-1.
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Antivirais/administração & dosagem , Heparitina Sulfato/administração & dosagem , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 3/efeitos dos fármacos , Ceratite Herpética/virologia , Regeneração , Animais , Materiais Biomiméticos , Células Cultivadas , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Ceratite Herpética/diagnóstico , Ceratite Herpética/tratamento farmacológico , Células Vero , Ensaio de Placa Viral , Replicação Viral/efeitos dos fármacosRESUMO
BackgroundHuman enteric viruses are resistant in the environment and transmitted via the faecal-oral route. Viral shedding in wastewater gives the opportunity to track emerging pathogens and study the epidemiology of enteric infectious diseases in the community. Aim: The aim of this study was to monitor the circulation of enteric viruses in the population of the Clermont-Ferrand area (France) by analysis of urban wastewaters. Methods: Raw and treated wastewaters were collected between October 2014 and October 2015 and concentrated by a two-step protocol using tangential flow ultrafiltration and polyethylene glycol precipitation. Processed samples were analysed for molecular detection of adenovirus, norovirus, rotavirus, parechovirus, enterovirus (EV), hepatitis A (HAV) and E (HEV) viruses. Results: All wastewater samples (n = 54) contained viruses. On average, six and four virus species were detected in, respectively, raw and treated wastewater samples. EV-positive samples were tested for EV-D68 to assess its circulation in the community. EV-D68 was detected in seven of 27 raw samples. We collected data from clinical cases of EV-D68 (n = 17), HAV (n = 4) and HEV infection (n = 16) and compared wastewater-derived sequences with clinical sequences. We showed the silent circulation of EV-D68 in September 2015, the wide circulation of HAV despite few notifications of acute disease and the presence in wastewater of the major HEV subtypes involved in clinical local cases. Conclusion: The environmental surveillance overcomes the sampling bias intrinsic to the study of infections associated with hospitalisation and allows the detection in real time of viral sequences genetically close to those reported in clinical specimens.
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Enterovirus/genética , Enterovirus/isolamento & purificação , Monitoramento Ambiental , Águas Residuárias/virologia , Microbiologia da Água , Enterovirus/classificação , Infecções por Enterovirus/virologia , Fezes/virologia , França/epidemiologia , Humanos , Projetos Piloto , Reação em Cadeia da Polimerase Via Transcriptase ReversaAssuntos
Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Cloridrato de Bendamustina/administração & dosagem , Hepatite E/complicações , Linfoma Folicular/complicações , Linfoma Folicular/tratamento farmacológico , Rituximab/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Combinação de Medicamentos , Evolução Fatal , Feminino , HumanosRESUMO
BACKGROUND & AIM: Several types of unexplained extra-hepatic manifestations, including haematological disorders, have been reported in the context of hepatitis E virus (HEV) infection. However, the underlying mechanism(s) of these manifestations are unknown. We provide evidence that HEV has an extra-hepatic endothelial tropism that can engage cutaneous T cells towards clonality. METHODS: A patient with a CD30(+) cutaneous T cell lymphoproliferative disorder (T-LPD) and biopsy-proven chronic HEV infection received three rounds of oral ribavirin treatment, administered either without or with interferon, and eventually achieved a sustained virologic response (SVR). Pathologic, virologic and immunologic investigations were carried out on biopsied skin lesion, and peripheral blood mononuclear cells between the 2nd and 3rd round of antiviral treatment and biopsied liver. RESULTS: Remission of T-LPD was observed upon antiviral treatment, and the patient remained in complete remission after achieving SVR. The T cell analysis showed large CD30(+) lymphocytes surrounding the blood vessels within the CD8(+) T cell infiltrate. HEV was detected within dermal microvascular endothelial cells using immunofluorescence staining, in situ hybridisation and electron microscopy. Infiltrating T cells mostly comprised memory CD8(+) T cells with a tissue-resident memory T cell phenotype. Overall, 98% of extracted T cells were CD8(+) T cells with aVß signature skewed towards Vß4 and with an oligoclonal profile. T cell clones from T-LPD were more like T cells in the liver than T cells in the blood [odds ratio=4.55, (3.70-5.60), p<0.0001]. No somatic mutations were found in the T-LPD exomes. CONCLUSION: HEV has an extra-hepatic tissue tropism in humans, including dermal endothelium, and can induce CD30(+) T-LPD that is sensitive to antivirals. LAY SUMMARY: Hepatitis E virus (HEV) has an extra-hepatic tissue tropism and should be added to the list of viruses associated with lymphoproliferative disorders. As such, HEV should be part of the laboratory workup of any lymphoproliferation, particularly those of the T cell phenotype that involve the skin. In the context of HEV-associated cutaneous T cell lymphoproliferative disorders, antiviral treatment could be considered a first-line treatment instead of chemotherapy.
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Hepatite E/complicações , Antígeno Ki-1/análise , Linfoma Cutâneo de Células T/etiologia , Neoplasias Cutâneas/etiologia , Vírus da Hepatite E/genética , Vírus da Hepatite E/isolamento & purificação , Humanos , Linfoma Cutâneo de Células T/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/virologia , Tropismo ViralRESUMO
BACKGROUND AND AIMS: In this French multicentre, open-label study, we analyzed the efficacy, safety and patient-reported outcomes of a boceprevir-based triple therapy in HCV genotype 1 cirrhotic patients awaiting liver transplantation (LT). METHODS: Patients received PEG-IFN/ribavirin (RBV) for 48 weeks (W) and boceprevir from W4 to W48 or until LT. RESULTS: Fifty-one patients (80% males, median age: 56 years) were included. Fifty-seven percent had hepatocellular carcinoma and 43% end-stage liver disease. At enrolment, the median MELD score was 9 (range: 6-18); the Child-Pugh score was A in 65%, B in 35% and C in 2%. Therapy was discontinued because of severe adverse events (SAEs) in 39% of cases and virological inefficacy in 24%. 16% of patients had undetectable HCV RNA 24 weeks after the end of treatment (SVR24). LT was performed in 18 patients (35%). HCV RNA was undetectable in 16.6% at LT. Seven patients (14%) died and three deaths were attributed to treatment. SAEs (n=129) were observed in 84% of patients. Twenty-four percent of patients developed severe infections. Albumin<35g/L was independently associated with severe infection. Compared with baseline values, a significant decrease (P=0.02) of the physical dimension of health-related quality of life was observed between W4 and W24. The mean (95% CI) number of self-reported symptoms doubled during treatment (from 6.3 [4.8-7.7] to 11.8 [9.3-14.3]; P<0.001). CONCLUSIONS: The safety of the PEG-IFN/RBV/boceprevir combination is poor in patients awaiting LT, with a high risk of severe infection. Moreover, the limited efficacy confirms the indication for IFN-free combinations in these patients.
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Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Transplante de Fígado , Prolina/análogos & derivados , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Quimioterapia Combinada , Feminino , França , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/mortalidade , Humanos , Interferon-alfa/uso terapêutico , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prolina/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resultado do TratamentoRESUMO
AIM: To identify risk factors associated with survival in patients retransplanted for hepatitis C virus (HCV) recurrence and to apply a survival score to this population. METHODS: We retrospectively identified 108 patients retransplanted for HCV recurrence in eight European liver transplantation centers (seven in France, one in Spain). Data collection comprised clinical and laboratory variables, including virological and antiviral treatment data. We then analyzed the factors associated with survival in this population. A recently published score that predicts survival in retransplantation in patients with hepatitis C was applied. Because there are currently no uniform recommendations regarding selection of the best candidates for retransplantation in this setting, we also described the clinical characteristics of 164 patients not retransplanted, with F3, F4, or fibrosing cholestatic hepatitis (FCH) post-first graft presenting with hepatic decompensation. RESULTS: Overall retransplantation patient survival rates were 55%, 47%, and 43% at 3, 5, and 10 years, respectively. Patients who were retransplanted for advanced cirrhosis had survival rates of 59%, 52%, and 49% at 3, 5, and 10 years, while those retransplanted for FCH had survival rates of 34%, 29%, and 11%, respectively. Under multivariate analysis, and adjusting for the center effect and the occurrence of FCH, factors associated with better survival after retransplantation were: negative HCV viremia before retransplantation, antiviral therapy after retransplantation, non-genotype 1, a Model for End-stage Liver Disease (MELD) score < 25 when replaced on the waiting list, and a retransplantation donor age < 60 years. Although the numbers were small, in the context of the new antivirals era, we showed that outcomes in patients who underwent retransplantation with undetectable HCV viremia did not depend on donor age and MELD score. The Andrés score was applied to 102 patients for whom all score variables were available, producing a mean score of 43.4 (SD = 6.6). Survival rates after the date of the first decompensation post-first liver transplantation (LT1) in the liver retransplantation (reLT) group (94 patients decompensated) at 3, 5, and 10 years were 62%, 59%, and 51%, respectively, among 78 retransplanted individuals with advanced cirrhosis, and 42%, 32%, and 16% among 16 retransplanted individuals with FCH. In the non-reLT group with hepatic decompensation, survival rates were 27%, 18%, and 9% at 3, 5, and 10 years, respectively (P < 0.0001). Compared with non-retransplanted patients, retransplanted patients were younger at LT1 (mean age 48 ± 8 years compared to 53 ± 9 years in the no reLT group, P < 0.0001), less likely to have human immunodeficiency virus (HIV) co-infection (4% vs 14% among no reLT patients, P = 0.005), more likely to have received corticosteroid bolus therapy after LT1 (25% in reLT vs 12% in the no reLT group, P = 0.01), and more likely to have presented with sustained virological response (SVR) after the first transplantation (20% in the reLT group vs 7% in the no reLT group, P = 0.028). CONCLUSION: Antiviral therapy before and after retransplantation had a substantial impact on survival in the context of retransplantation for HCV recurrence, and with the new direct-acting antivirals now available, outcomes should be even better in the future.
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Técnicas de Apoio para a Decisão , Hepacivirus/patogenicidade , Hepatite C/cirurgia , Cirrose Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Ativação Viral , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , França , Hepatite C/diagnóstico , Hepatite C/mortalidade , Hepatite C/virologia , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Recidiva , Reoperação , Estudos Retrospectivos , Fatores de Risco , Espanha , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Antiviral therapy using newer nucleos(t)ide analogues with lower resistance rates, such as entecavir or tenofovir, suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or decompensated cirrhosis, and delay or obviate the need for liver transplantation in some patients. After liver transplantation, the combination of long-term antiviral and low-dose hepatitis B Immune globulin (HBIG) can effectively prevent HBV recurrence in greater than 90% of transplant recipients. Some forms of HBV prophylaxis need to be continued indefinitely after transplantation but, in patients with a low-risk of HBV recurrence (i.e., HBV DNA levels undetectable before transplantation), it is possible to discontinue HBIG and maintain only long-term nucleos(t)ide analogue(s) therapy. A more cautious approach is necessary for those patients with high pretransplant HBV DNA levels, those with limited antiviral options if HBV recurrence occurs (i.e., HIV or hepatitis D virus coinfection, preexisting drug resistance), those with a high risk of hepatocellular carcinoma recurrence, and those at risk of noncompliance with antiviral therapy. In this group, HBIG-free prophylaxis cannot be recommended.
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Antivirais/administração & dosagem , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Imunoglobulinas/administração & dosagem , Cirrose Hepática/cirurgia , Transplante de Fígado , Prevenção Secundária/métodos , Antivirais/efeitos adversos , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite B/virologia , Vacinas contra Hepatite B/efeitos adversos , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Imunoglobulinas/efeitos adversos , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Transplante de Fígado/efeitos adversos , Recidiva , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Ativação Viral/efeitos dos fármacosRESUMO
The clinical presentation and outcome of hepatitis E virus (HEV) infection in inflammatory rheumatic diseases are unknown. We aimed to investigate the severity of acute HEV infection and the risk of chronic viral replication in patients with inflammatory arthritides treated with immunosuppressive drugs. All rheumatology and internal medicine practitioners belonging to the Club Rhumatismes et Inflammation in France were sent newsletters asking for reports of HEV infection and inflammatory arthritides. Baseline characteristics of patients and the course of HEV infection were retrospectively assessed by use of a standardized questionnaire. From January 2010 to August 2013, we obtained reports of 23 cases of HEV infection in patients with rheumatoid arthritis (nâ=â11), axial spondyloarthritis (nâ=â5), psoriatic arthritis (nâ=â4), other types of arthritides (nâ=â3). Patients received methotrexate (nâ=â16), antitumor necrosis factor α agents (nâ=â10), rituximab (nâ=â4), abatacept (nâ=â2), tocilizumab (nâ=â2), and corticosteroids (nâ=â10, median dose 6âmg/d, range 2-20). All had acute hepatitis: median aspartate and alanine aminotransferase levels were 679 and 1300âU/L, respectively. Eleven patients were asymptomatic, 4 had jaundice. The HEV infection diagnosis relied on positive PCR results for HEV RNA (nâ=â14 patients) or anti-HEV IgM positivity (nâ=â9). Median follow-up was 29 months (range 3-55). Treatment included discontinuation of immunosuppressants for 20 patients and ribavirin treatment for 5. Liver enzyme levels normalized and immunosuppressant therapy could be reinitiated in all patients. No chronic infection was observed. Acute HEV infection should be considered in patients with inflammatory rheumatism and elevated liver enzyme values. The outcome of HEV infection seems favorable, with no evolution to chronic hepatitis or fulminant liver failure.
Assuntos
Artrite/complicações , Hepatite E/induzido quimicamente , Imunossupressores/efeitos adversos , Adulto , Idoso , Antivirais/uso terapêutico , Artrite/tratamento farmacológico , Artrite/virologia , Feminino , França , Hepatite E/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Hepatitis E virus (HEV) infection is a known cause of acute-on-chronic liver failure in developing countries, but its implication in Western countries remains unknown. HEV burden in the setting of severe acute alcoholic hepatitis (AAH) was assessed. METHODS: Patients admitted for severe AAH from 2007 to 2013, with available sera and histologically proven AAH, were included and managed according to current European guidelines. At admission, clinical and biological characteristics were collected; HEV serology and RNA detection were retrospectively performed. RESULTS: Eighty-four patients were included. Mean age was 50.8 ± 9.6 years, 65.5% were male, 91.7% were cirrhotic and 33.3% presented with encephalopathy. Mean MELD and Maddrey scores were respectively 32.4 ± 11.4 and 73.3 ± 37. Liver biopsy showed mild, moderate and severe hepatitis in 25 (29.8%), 23 (27.4%) and 32 (38.1%) patients respectively. Steroids were given to 61 patients (72.6%) of whom 35 (57.4%) presented corticoresistance (mean Lille score: 0.78 ± 0.21). During hospitalization, 24 patients (28.6%) died and 11 (13.1%) were transplanted. Three patients (3.6%) presented markers of acute HEV infection and 21 (25%) markers of past HEV infection. Patient with acute infection were men, cirrhotic, and 2/3 presented with encephalopathy. Steroids were given to two patients without any response. The third patient died. None were transplanted. CONCLUSIONS: A substantial proportion of patients with severe AAH had markers of acute HEV infection, with similar clinical presentation and outcomes. Larger studies are needed to evaluate HEV impact on AAH management, resistance to steroids, and outcome.