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The objectives of this study were to evaluate incidence and to identify the risk factors of occurrence and the predictive factors of symptomatic forms of nodular regenerative hyperplasia (NRH) after liver transplantation (LT).To identify risk factors of NRH following LT, we included 1648 patients transplanted from 2004 to 2018 and compared the patients developing NRH after LT to those who did not. To identify predictive factors of symptomatic NRH, we selected 115 biopsies displaying NRH and compared symptomatic to asymptomatic forms. Symptomatic NRH was defined as the presence of ascites, esophageal varices, hepatic encephalopathy, portal thrombosis, retransplantation, or death related to NRH.The incidence of NRH following LT was 5.1%. In multivariate analysis, the independent factor of developing NRH after LT was the donor's age (odds ratio [OR] = 1.02; confidence interval, 1.01-1.03; P = 0.02). Symptomatic forms occurred in 29 (25.2%) patients: 19 (16.5%) patients presented with ascites, 13 (11.3%) with esophageal varices, 4 (3.5%) with hepatic encephalopathy, and 8 (7%) with portal thrombosis. The median period before the onset of symptoms was 8.4 (1.5-11.3) y after LT. The spleen size at diagnosis/before LT ratio (OR = 12.5; 114.17-1.37; P = 0.0252) and thrombectomy during transplantation (OR = 11.17; 1.48-84.11; P = 0.0192) were associated with symptomatic NRH in multivariate analysis.NRH following LT is frequent (5.1%) and leads to symptomatic portal hypertension in 25.2% of patients. Using older grafts increases the risk of developing NRH after LT. Clinicians should screen for signs of portal hypertension, particularly in measuring spleen size.

BackgroundTo date, the usage of Galaxy, an open-source bioinformatics platform, has been reported primarily in research. We report 5 years’ experience (2015 to 2020) with Galaxy in our hospital, as part of the “Assistance Publique–Hôpitaux de Paris” (AP-HP), to demonstrate its suitability for high-throughput sequencing (HTS) data analysis in a clinical laboratory setting.MethodsOur Galaxy instance has been running since July 2015 and is used daily to study inherited diseases, cancer, and microbiology. For the molecular diagnosis of hereditary diseases, 6970 patients were analyzed with Galaxy (corresponding to a total of 7029 analyses).ResultsUsing Galaxy, the time to process a batch of 23 samples—equivalent to a targeted DNA sequencing MiSeq run—from raw data to an annotated variant call file was generally less than 2 h for panels between 1 and 500 kb. Over 5 years, we only restarted the server twice for hardware maintenance and did not experience any significant troubles, demonstrating the robustness of our Galaxy installation in conjunction with HTCondor as a job scheduler and a PostgreSQL database. The quality of our targeted exome sequencing method was externally evaluated annually by the European Molecular Genetics Quality Network (EMQN). Sensitivity was mean (SD)% 99 (2)% for single nucleotide variants and 93 (9)% for small insertion-deletions.ConclusionOur experience with Galaxy demonstrates it to be a suitable platform for HTS data analysis with vast potential to benefit patient care in a clinical laboratory setting.

Prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is based on administration of vaccine and immunoglobulins (HBIg) to newborns at birth and maternal antiviral prophylaxis for those with an HBV-DNA viral load of at 5·3 logTA-PROHM was a single-arm, multicentre, phase 4 trial done in five maternity units in Cambodia. Pregnant women who were positive for hepatitis B surface antigen (HBsAg), aged 18 years or older were included. Women who were HCV or HIV positive, had creatinine clearance of less than 30 mL/min, severe gravid disease, and planned to give birth outside the study sites were excluded. From Oct 4, 2017, to Jan 9, 2019, HBsAg positive pregnant women who tested positive for hepatitis B e antigen (HBeAg) with a rapid diagnostic test were eligible to receive tenofovir disoproxil fumarate. From Jan 9, 2019, women who were HBeAg negative with an alanine aminotransferase concentration of ≥40 IU/L were also eligible to receive tenofovir disoproxil fumarate. Women in the tenofovir disoproxil fumarate eligible group received 300 mg of tenofovir disoproxil fumarate orally once a day from the 24th week of gestation until 6 weeks postpartum. The primary outcome was the overall proportion of infants who were HBsAg positive at 6 months of life, confirmed by positive HBV DNA quantification. For the primary outcome, the proportion (95% CI) of infants with HBsAg at 6 months was stratified according to infant's HBIg status, duration of maternal tenofovir disoproxil fumarate treatment (4 weeks and ≤4 weeks), and study period (before and after the change in therapeutic algorithm) and was measured in a modified intention-to-treat analysis, which excluded infants lost to follow-up or who were withdrawn before 6 months. The study is registered with ClinicalTrials.gov, NCT02937779.From Oct 4, 2017, to Nov 27, 2020, 21 251 pregnant women were screened for HBsAg, of whom 1194 (6%) were enrolled in the study: 338 (28%) were eligible to receive tenofovir disoproxil fumarate. For the tenofovir disoproxil fumarate eligible group, four (1% [95% CI 0·34-3·20]) of 317 infants had HBV infection at 6 months; in the subgroup of 271 children who did not receive HBIg, four (1% [0·40-3·74]) had HBV infection at 6 months. In absence of HBIg, MTCT HBV transmission occurred in none (0% [0-1·61]) of 227 women who received tenofovir disoproxil fumarate for more than 4 weeks before giving birth and three (8% [1·75-22·47]) of 36 women who received tenofovir disoproxil fumarate for less than 4 weeks. In the tenofovir disoproxil fumarate ineligible group, seven (1% [0·40-2·02]) of 712 infants had HBV infection at 6 months; in the subgroup of 567 children who did not receive HBIg, six (1% [0·39-2·30]) had HBV infection at 6 months.An immunoglobulin-free strategy using an HBeAg rapid diagnosis test and alanine aminotransferase-based algorithm to assess eligibility for tenofovir, is effective at preventing MTCT of HBV when tenofovir was initiated at least 4 weeks before birth.French Agency for Research on AIDS and Viral Hepatitis and Emerging Infectious diseases.For the French translation of the abstract see Supplementary Materials section.

BACKGROUND DATA In compensated cirrhotics with early hepatocellular carcinoma (HCC-cirr), upfront liver resection (LR) and salvage liver transplantation (SLT) in case of recurrence may have outcomes comparable to primary LT (PLT). OBJECTIVE An intention-to-treat (ITT) analysis comparing PLT and SLT strategies. METHODS Of 130 HCC-cirr patients who underwent upfront LR (group LR), 90 (69%) recurred, 31 could undergo SLT (group SLT). During the same period, 366 patients were listed for LT (group LLT); 26 dropped-out (7.1%), 340 finally underwent PLT (group PLT). We compared survival between groups LR and LLT, LR and PLT, and PLT and SLT. RESULTS Feasibility of SLT strategy was 34% (31/90). In an ITT analysis, group LLT had better 5-yr/10-yr overall survival (OS) compared with group LR (68%/58% vs. 58%/35%; P = 0.008). Similarly, 5-yr/10-yr OS and disease-free survival (DFS) were better in group PLT versus group LR (OS 73%/63% vs. 58%/35%, P = 0.0007; DFS 69%/61% vs. 27%/21%, P

Additional file 3: Table S3. Gene Ontology distribution of proteins recognized by CC sera, according to the protein class.

Antiviral therapy after liver transplantation (LT) using interferon (IFN) and ribavirin (RBV) can achieve a sustained virological response (SVR) rate ranging from 20% to 45%. The aims of our study were to assess efficacy and tolerability of therapy, effect on fibrosis progression and the importance of the initial fibrosis stage to outcome. A total of 113 hepatitis C virus (HCV)-infected LT patients received 133 courses of IFN (standard, n = 29, pegylated IFN [pegIFN], n = 104) and RBV (75% genotype 1). Early virological response (EVR), end-of-treatment (EOT), and SVR were obtained in 74%, 55%, and 38%, respectively. EVR, completion of treatment, viral load before therapy, genotype non-1, and use of pegIFN were predictive of SVR, but only EVR remained in the multivariate analysis. SVR was obtained in 45% patients who received a second course of therapy. Paired biopsies at baseline, at EOT and at long-term were available in 42 patients. The mean fibrosis stage remained stable in patients with SVR and increased in patients without response. Rejection episodes were observed in 6% of patients. Tolerability of therapy decrease in patients with fibrosis stageor =3 on baseline liver biopsy. A total of 20% of them died or were retransplanted due to liver failure as opposed to 1% of patients who had fibrosis stage3. In conclusion, IFN and RBV achieved SVR in 38% of patients. EVR is independently associated with SVR. Fibrosis stage remained stable in patients with SVR and increased in nonresponders. Fibrosis stageor =3 was associated with a high rate of liver failure, arguing for an early introduction of antiviral therapy.