Transplantation hépatique pédiatrique et séroprévalence du virus de l'hépatite E

L'hépatite E (HE) est une maladie émergente dans les pays développés. Elle est souvent asymptomatique, surtout chez l'enfant. Un passage à la chronicité est possible chez les immunodéprimés. L'HE peut mimer un rejet de greffe. La prise en charge, différente, souligne l'importance du diagnostic chez le transplanté. Nous avons conduit cette étude de prévalence car les données pédiatriques sont pauvres en France. Dans cette étude retrospective menée à Lyon entre le 1er janvier 2010 et le 31 mai 2013, nous avons étudié la sérologie (IgG et IgM) et la PCR du virus de l'HE (VHE) chez 96 patients (84 transplantés hépatique et 12 transplantés Foie+Rein). Huit patients (8,3%, 62,5% filles, âge moyen 12,3 ans) était séropositifs. L'âge moyen post transplantation était de 10 ans (2-21 ,8 ans). L'étiologie principale de la transplantation était l'atrésie des voies biliaires. Sept d'entre eux étaient transplantés hépatiques. Il n'est pas retrouvé de différence entre les données épidémiologiques et cliniques de la population séropositive et celles de l'ensemble des greffés, en particulier sur l'immunosuppression (7/8 tacrolimus-50% bi thérapie). Il n'a pas été détecté d'HE chronique mais 1 patient présentait une cytolyse chronique (Adénovirus et EBV). Pour au moins 4/8 des patients la séroconversion a eu lieu après la transplantation. Il n'y a pas de différence de séroprévalence selon l'âge (0% <5 ans, 12,5%5-10 ans, 4% 10-15 ans, 9,1o/ô 15-20 ans et 12,5% >20 ans). En France, la prévalence de l'infection à HE chez les transplantés hépatique pédiatrique (ou foie/rein) est faible (8,3%). Elle est concordante avec les données européennesLYON1-BU Santé (693882101) / SudocSudocFranceF

Transplantation hépatique pédiatrique et séroprévalence du virus de l'hépatite E

L'hépatite E (HE) est une maladie émergente dans les pays développés. Elle est souvent asymptomatique, surtout chez l'enfant. Un passage à la chronicité est possible chez les immunodéprimés. L'HE peut mimer un rejet de greffe. La prise en charge, différente, souligne l'importance du diagnostic chez le transplanté. Nous avons conduit cette étude de prévalence car les données pédiatriques sont pauvres en France. Dans cette étude retrospective menée à Lyon entre le 1er janvier 2010 et le 31 mai 2013, nous avons étudié la sérologie (IgG et IgM) et la PCR du virus de l'HE (VHE) chez 96 patients (84 transplantés hépatique et 12 transplantés Foie+Rein). Huit patients (8,3%, 62,5% filles, âge moyen 12,3 ans) était séropositifs. L'âge moyen post transplantation était de 10 ans (2-21 ,8 ans). L'étiologie principale de la transplantation était l'atrésie des voies biliaires. Sept d'entre eux étaient transplantés hépatiques. Il n'est pas retrouvé de différence entre les données épidémiologiques et cliniques de la population séropositive et celles de l'ensemble des greffés, en particulier sur l'immunosuppression (7/8 tacrolimus-50% bi thérapie). Il n'a pas été détecté d'HE chronique mais 1 patient présentait une cytolyse chronique (Adénovirus et EBV). Pour au moins 4/8 des patients la séroconversion a eu lieu après la transplantation. Il n'y a pas de différence de séroprévalence selon l'âge (0% 20 ans). En France, la prévalence de l'infection à HE chez les transplantés hépatique pédiatrique (ou foie/rein) est faible (8,3%). Elle est concordante avec les données européennesLYON1-BU Santé (693882101) / SudocSudocFranceF

Maternal uniparental disomy 14 revealed by alpha 1 antitrypsin deficiency

International audienceAlpha 1 antitrypsin deficiency (AATD) is an autosomal co-dominant disease linked to a mutation of the SERPINA1 gene localized to chromosome 14q32. Uniparental disomy (UPD) is known to be a genetic mechanism that causes various syndromes. Maternal UPD14 presents with a Prader-Willi syndrome-like phenotype. No publications to date have dealt with the association of these two syndromes. In this article, we report on two cases of AATD (from different families), which lead to the diagnosis of maternal UPD14. AATD was diagnosed early in both children. Their clinical presentations were typical (chronic cytolysis in patient 1 and neonatal cholestasis in patient 2); serum alpha 1 antitrypsin levels were low (P1 0.33g/L and P2 0.35g/L), and both patients had a Z phenotype. A pedigree study of both families showed that the father had an M phenotype and the mother an MZ phenotype, which was unexpected. On the other hand, both children were born before term and presented with symmetrical growth retardation, early eating difficulties, moderate hypotonia, understated dysmorphic features and moderate psychomotor retardation, suggestive of a Prader-Willi syndrome-like phenotype. Genotyping was performed to explain gene transmission inconsistencies, and highlighted maternal UPD 14 in both families. CONCLUSION: Logically, maternal UPD 14 can induce AATD. In light of these observations, it seems appropriate to search for AATD in patients with maternal UPD 14 in order to prevent a progression of the disease. These cases also underline the significance of maternal UPD 14, which should be suspected in AATD in view of the discordance with Mendel's allelic transmission law

Are protocol graft biopsies after pediatric liver transplantation useful? Experience in a single center over 20 years

Abstract Background The role of protocol liver biopsies (PLB) in the follow‐up of pediatric liver transplant recipients remains questionable. This single‐center retrospective study aimed to evaluate their clinical impact on the long‐term management of pediatric liver transplant recipients. Methods We described histopathological lesions and clinical consequences for patient management of PLB performed 1, 5, 10, 15, 20, and 25 years after pediatric liver transplantation (LT). Results A total of 351 PLB performed on 133 patients between 1992 and 2021 were reviewed. PLB found signs of rejection in 21.7% of cases (76/351), and moderate to severe fibrosis in 26.5% of cases (93/351). Overall, 264 PLB (75.2%) did not cause any changes to patient care. Immunosuppression was enhanced after 63 PLB, including 23 cases of occult rejection. The 1‐year PLB triggered significantly more changes, while biopsies at 15, 20, and 25 years produced the lowest rates of subsequent modifications. PLB had a significantly higher probability of inducing therapeutic changes if the patient had abnormal biological or imaging results (odds ratio [OR] 2.82 and 2.06), or a recent history of rejection or bacterial infection (OR 2.22 and 2.03). Conclusion Our results suggest that, although it often does not prompt any treatment changes, PLB could be performed because of its ability to detect silent rejection requiring an increase in immunosuppression. PLB could be carried out 1, 5, and 10 years after LT and then every 10 years in patients with normal biological and imaging results and no recent complications, while other patients could be kept on a 5‐year protocol

Covid-19 in liver transplant recipients: the French SOT COVID registry

International audienceBackground: Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in organ transplant recipients remains limited. The aim of this registry-based observational study was to report the characteristics and clinical outcomes of liver transplant (LT) recipients included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19.Methods: COVID-19 was diagnosed in patients who had a positive PCR assay for SARS-CoV-2 or in presence of typical lung lesions on imaging or specific SARS-CoV-2 antibodies. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded.Results: Of the 104 patients, 67 were admitted to hospital and 37 were managed at home (including all 13 children). Hospitalized patients had a median age of 65.2 years (IQR: 58.1 - 73.2 years) and two thirds were men. Most common comorbidities included overweight (67.3%), hypertension (61.2%), diabetes (50.7%), cardiovascular disease (20.9%) and respiratory disease (16.4%). SARS-CoV-2 infection was identified after a median of 92.8 months (IQR: 40.1 - 194.7 months) from LT. During hospitalization, antimetabolites, mTOR inhibitor, and CNIs were withdrawn in 41.9%, 30.0% and 12.5% of patients, respectively. The composite endpoint of severe Covid-19 within 30 days after diagnosis was reached by 33.0% of the adult patients. The 30-day mortality rate was 20.0%, and 28.1% for hospitalized patients. Multivariate analysis identified that age was independently associated with mortality.Conclusion: In our large nationwide study, Covid-19 in LT recipients was associated with a high mortality rate

Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency

Mutations in ATP8B1 can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1 (PFIC1). The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide novel insights by using the largest genetically defined cohort of FIC1 deficiency patients to date. This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication); FIC1-A (n=67; no PPTM), FIC1-B (n=29; one PPTM) or FIC1-C (n=34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18y. NLS was comparable between FIC1-A, FIC1-B, and FIC1-C (%NLS at age 10y: 67%, 41%, and 59%, respectively; P=0.12), despite FIC1-C undergoing SBD less often (%SBD at age 10y: 65%, 57%, and 45%, respectively; P=0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10y; sBAs <194 µmol/L: 49% versus sBAs ≥194 µmol/L: 15%; P=0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] μmol/L; P=0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P=0.06) and post-SBD sBA concentrations <65μmol/L (P=0.05) tended to be associated with improved NLS. Conclusion: Less than half of FIC1 deficiency patients reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS