Late-onset enteric virus infection associated with hepatitis (EVAH) in transplanted SCID patients.

BACKGROUND: Allogenic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are potentially curative treatments for severe combined immunodeficiency (SCID). Late-onset posttreatment manifestations (such as persistent hepatitis) are not uncommon. OBJECTIVE: We sought to characterize the prevalence and pathophysiology of persistent hepatitis in transplanted SCID patients (SCIDH+) and to evaluate risk factors and treatments. METHODS: We used various techniques (including pathology assessments, metagenomics, single-cell transcriptomics, and cytometry by time of flight) to perform an in-depth study of different tissues from patients in the SCIDH+ group and corresponding asymptomatic similarly transplanted SCID patients without hepatitis (SCIDH-). RESULTS: Eleven patients developed persistent hepatitis (median of 6 years after HSCT or GT). This condition was associated with the chronic detection of enteric viruses (human Aichi virus, norovirus, and sapovirus) in liver and/or stools, which were not found in stools from the SCIDH- group (n = 12). Multiomics analysis identified an expansion of effector memory CD8+ T cells with high type I and II interferon signatures. Hepatitis was associated with absence of myeloablation during conditioning, split chimerism, and defective B-cell function, representing 25% of the 44 patients with SCID having these characteristics. Partially myeloablative retransplantation or GT of patients with this condition (which we have named as "enteric virus infection associated with hepatitis") led to the reconstitution of T- and B-cell immunity and remission of hepatitis in 5 patients, concomitantly with viral clearance. CONCLUSIONS: Enteric virus infection associated with hepatitis is related to chronic enteric viral infection and immune dysregulation and is an important risk for transplanted SCID patients with defective B-cell function.

Pregnancy in women on chronic dialysis in the last decade (2010-2020): a systematic review.

Background: Pregnant women with end-stage renal disease on chronic dialysis are at a high risk of maternal and foetal complications. Over the years, the prognosis of their pregnancies has improved with advances in dialysis treatments and maternal and neonatal care. We conducted this systematic review to examine the recent data on maternal and foetal outcomes in pregnant women with end-stage renal failure on chronic dialysis over the last decade. Methods: We made a systematic review of studies on pregnant women on chronic dialysis published between 1 January 2010 and 31 December 2020. We searched the following electronic databases: Medline via PubMed, Embase and the Cochrane Library, with search strategies for each database. We checked the titles and abstracts identified by the search equation, and two independent reviewers assessed the articles retrieved. For each study, the two reviewers separately recorded the data from each selected article on a standardized data extraction form. For each article, we recorded relevant general information on the study, patient demographic characteristics, dialysis schedule, pregnancy complications and outcomes, maternal complications, and foetal and neonatal outcomes. Results: The literature search yielded 1668 potentially relevant abstracts. After reviewing the titles, abstracts and full text, we identified 14 studies according to the inclusion criteria. All studies were observational, nine of them were retrospective and eight were from a single-centre experience. The total number of women included in these studies was 2364 (range 8-2008) and the total number of pregnancies was 2754 (range 8-2352). The patients' ages ranged from 15 to 45 years. Obesity was observed in 808 (34.2%) women and ranged from 1 to 778. Haemodialysis was the predominant modality with 2551 (92.6%) pregnancies, and 203 (7.4%) on peritoneal dialysis. Overall, 68 out of 402 (16.9%) spontaneous miscarriages, 21 out of 402 (5.2%) therapeutic abortions and 26 (8.3%) stillbirths among 313 (stillbirths and live births) were recorded. The mean or median gestational age at delivery ranged from 25.2 to 36 weeks. The main maternal complications were preeclampsia 11.9%, hypertension 7.7% and anaemia 3.9%. Live births represented 287 (71.4%) out of 402 pregnancies, birth weight ranged from 590 to 3500 g and preterm birth was the main, most common complication in all studies, ranging from 50% to 100%. Intrauterine growth restriction was present in 5.9% and small-for-gestational-age was reported in 18.9% of neonates. There were 22 (7.6%) neonatal deaths among 287 live births and 48 (15.3%) perinatal deaths among 313 total births (stillbirths and live births). Conclusions: Presumably, considering the increase in the number of publications and the total number of pregnancies reported therein, the frequency of pregnancy in patients with end-stage chronic kidney disease treated by chronic dialysis has increased. However, the practice of treating pregnant women on dialysis differs significantly among countries. These findings highlight the need to standardize the definition of outcomes and healthcare for pregnant women on dialysis.