Ségolène Brichler

Hepatitis delta (HDV) infection affects 5% of hepatitis B (HBV)-positive patients and is associated with an increased risk of cirrhosis and hepatocellular carcinoma; however, it remains underdiagnosed. The first part of our Delta Describe study highlights the insufficient level of HDV screening among patients in metropolitan France. In this study, we report on their real-world management. Patients with at least one positive HDV RNA test performed in 2019 were identified through the major public and private laboratories in France. From January 2024 to July 2025, informed patients were interviewed, and physicians supplemented the collected data. A total of 547 patients were included, with a median age of 44 years; most originated from Africa or Eastern Europe. HIV and hepatitis C coinfections were reported in 15.2% and 4.6% of patients, respectively. Liver fibrosis was primarily assessed using FibroScan^®. Most patients knew the year of their delta diagnosis, and 69.1% knew their fibrosis stage. Liver-related events occurred in 14.3% (67/468) of patients, mainly comprising portal hypertension (61.6%), liver failure (12.3%), and hepatocellular carcinoma (26%), and 45 patients (45/468) underwent liver transplantation. At the time of the survey, 47.1% of the patients reported undetectable HDV RNA; 40.6% (222/547) had currently or previously undergone BLV treatment. Among patients receiving ongoing treatment for HDV at the time of the survey, 84.8% were receiving nucleos(t)ide analogs (NUCs). In metropolitan France, HDV patients had access to specialized follow-up care and innovative therapies (bulevirtide), were mostly on NUCs, and demonstrated good disease awareness.

Hepatitis delta (HDV) infection affects 5% of hepatitis B (HBV)-positive patients, is associated with an increased risk of cirrhosis and hepatocellular carcinoma but remains underdiagnosed. The first part of our « Delta Describe » study highlighted insufficient screening of HDV patients in metropolitan France. We report here their real-world management. Patients with at least one positive HDV RNA test performed in 2019 were identified through the main French public and private laboratories. In 2024, informed patients were interviewed and physicians supplemented the collected data. 547 patients were included, median age 44 years, mainly originated from Africa or Eastern Europe. HIV and Hepatitis C coinfections were reported in 15.2% and 4.6% respectively. Liver stiffness was assessed by FibroScan® (75.3%) primarily. Most patients knew the year of diagnosis and 69% their fibrosis stage. Liver related events occurred in 14.3% of patients, mainly cirrhosis decompensation (67.9%) and hepatocellular carcinoma (28.3%). Forty-five patients underwent liver transplantation. In 2024, 47.5% had undetectable HDV RNA. Among treated patients (n=387), 37.4% received bulevirtide with or without pegylated-interferon, and 62.6% nucleos(t)ide analogues (NUCs) only. In metropolitan France, HDV patients had access to specialized follow-up, to innovative therapies (bulevirtide), were mostly on NUCs and demonstrated good disease awareness.

Background: Neutralizing antibodies targeting the SARS-CoV-2 Spike protein reduce COVID-19-related risk of hospitalization, particularly in high-risk individuals. The COCOPREV-R study aimed to evaluate and compare clinical outcomes in high-risk SARS-CoV-2 patients treated with dual monoclonal antibody therapies and to identify associated virological factors. Methods: The COCOPREV-R study retrospectively collected real-world data from high-risk patients receiving Bamlanivimab/Etesevimab or Casirivimab/Imdevimab dual monoclonal antibody therapies (22 February 2021 to 15 June 2021). Results: The study included 1004 patients with COVID-19, of whom 691 received Bamlanivimab/Etesevimab and 313 received Casirivimab/Imdevimab. The alpha variant represented 90.1% of those for whom data were available. The risk of hospitalization within 30 days was lower with Bamlanivimab/Etesevimab (12.7%, CI 95% [9.9–16.3%]) compared to Casirivimab/Imdevimab (28.4%, CI 95% [22.7–35.1%) (p < 0.001). The 30-day mortality rates were comparable between both groups (p = 0.982). Analysis of SARS-CoV-2 PCR negativity showed no difference between the two treatment groups (95.2% [93.0–96.9%] and 93.5% [89.1–96.6%] until day 30, p = 0.851 for Bamlanivimab/Etesevimab and Casirivimab/Imdevimab, respectively). Among persistently positive samples with available sequencing results (n = 43), Spike protein changes occurred only in Bamlanivimab/Etesevimab (42.9%) vs. Casirivimab/Imdevimab (0.0%) groups. Q493R (25.0%) and E484K (12.5%) were the most common mutations selected by Bamlanivimab/Etesevimab in follow-up samples. Other factors (immunodepression, comorbidities, and age) did not appear to be associated with the occurrence of Spike protein mutations. Conclusions: A higher rate of hospitalization was seen with Casirivimab/Imdevimab (RONAPREVE^®) in comparison with Bamlanivimab/Etesevimab treatment, but with the emergence of Spike mutations only in the Bamlanivimab/Etesevimab group.

Hepatitis delta virus (HDV) is a satellite of hepatitis B virus (HBV), which requires the HBV surface antigen (HBsAg) for its assembly and propagation. Although countries affected by HBV infection in Africa are well identified, data on HDV infection are still scarce, like in Nigeria, where HBV infection is endemic. In this study, we aimed to determine the prevalence of HDV infection and identify the circulating genotypes/strains in the country. A nationwide study was performed on 1281 HBsAg-positive samples collected from patients across eleven sites drawn from the six geopolitical zones in Nigeria. Anti-HDV antibody (HDV-Ab) screening and HDV-RNA viral load quantification were performed using a commercial ELISA assay and real-time RT-PCR kit, respectively. HDV genotyping was performed by the Sanger sequencing of amplicons from the so-called R0 region of the viral genome, followed by phylogenetic analyses. Of the 1281 HBsAg-positive samples, 61 (4.8%) were HDV-Ab positive, among which, 12 (19.7%) were HDV-RNA positive. Genotypes were obtained for nine of them: seven “African” HDV-1, one “Asian/European” HDV-1 and one HDV-6. This study shows that Nigeria is a country of low HDV prevalence where mainly “African” genotype-1 strains are circulating.

The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3–8] vs. 3 [2–4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.

Background: Infants with COVID-19 can often present with fever without source, which is a challenging situation in infants <90 days old. The “step-by-step” algorithm has been proposed to identify children at high risk of bacterial infection. In the context of the COVID-19 pandemic, we aimed to reassess the diagnostic performance of this algorithm. Methods: We performed a multicentric retrospective study in 3 French pediatric emergency departments between 2018 and 2020. We applied the “step-by-step” algorithm to 4 clinical entities: COVID-19, febrile urinary tract infections (FUTI), invasive bacterial infection (IBI), and enterovirus infections. The main outcome was the proportion of infants classified at high risk (ill-appearing, ≤21 days old, with leukocyturia or procalcitonin level ≥0.5 ng/mL). Results: Among the 199 infants included, 40 had isolated COVID-19, 25 had IBI, 60 had FUTI, and 74 had enterovirus infection. All but 1 infant with bacterial infection were classified at high risk (96% for IBI and 100% for FUTI) as well as 95% with enterovirus and 82% with COVID-19. Infants with COVID-19 were classified at high risk because an ill-appearance (72%), an age ≤21 days (27%), or leukocyturia (19%). All these infants had procalcitonin values 20 mg/L. Conclusions: The “step-by-step” algorithm remains effective to identify infants with bacterial infection but misclassifies most infants with COVID-19 as at high risk of bacterial infection leading to unnecessary cares. An updated algorithm based adding viral testing may be needed to discriminate fever related to isolated COVID-19 in infants <90 days old.

Human hepatitis delta virus (HDV) is a small defective RNA satellite virus that requires hepatitis B virus (HBV) envelope proteins to form its own virions. The HDV genome possesses a single coding open reading frame (ORF), located on a replicative intermediate, the antigenome, encoding the small (s) and the large (L) isoforms of the delta antigen (s-HDAg and L-HDAg). The latter is produced following an editing process, changing the amber/stop codon on the s-HDAg-ORF into a tryptophan codon, allowing L-HDAg synthesis by the addition of 19 (or 20) C-terminal amino acids. The two delta proteins play different roles in the viral cell cycle: s-HDAg activates genome replication, while L-HDAg blocks replication and favors virion morphogenesis and propagation. L-HDAg has also been involved in HDV pathogenicity. Understanding the kinetics of viral editing rates in vivo is key to unravel the biology of the virus and understand its spread and natural history. We developed and validated a new assay based on next-generation sequencing and aimed at quantifying HDV RNA editing in plasma. We analyzed plasma samples from 219 patients infected with different HDV genotypes and showed that HDV editing capacity strongly depends on the genotype of the strain.

Summary: Worldwide, hepatocellular carcinoma (HCC) occurs mainly in Asian patients with hepatitis B virus (HBV) infection. This study aimed to decipher the environmental and virological factors associated with HCC occurrence and validate risk scoring systems in a French multicentre prospective cohort of HBV cirrhotic patients. Patients with biopsy‐proven Child‐Pugh A viral cirrhosis included in the ANRS CO12 CirVir cohort who were HBsAg(+) without hepatitis C coinfection were selected for: (a) interview through a standardized questionnaire reporting coffee consumption and HCC familial history; (b) HBsAg quantification using baseline and sequential 2‐year frozen sera; (c) baseline HBV genotype determination; and (d) assessment of risk factors and applicability of HCC risk scores (Kaplan‐Meier analysis, Cox models). Among 317 patients studied (261 men, median age 53 years, past or ongoing antiviral treatment 93.3% and baseline detectable HBV DNA in 88 patients), the baseline and 2‐year median HBsAg levels were 810 and 463 IU/mL, respectively. After a median follow‐up of 65.2 months, 27 HCC cases were diagnosed (annual incidence: 1.6%). Three factors were independently associated with HCC occurrence: age > 50 years, platelets ≤ 150 × 10³/mm³ and body mass index ≥ 30 kg/m². Two out of five risk scores were validated, and the most accurate was PAGE‐B at 1 year. Moreover, HCC in patients without maintained virological suppression seems more aggressive and less accessible to curative treatment. In conclusion, in French patients with HBV cirrhosis mostly virally suppressed, independent HCC risk factors were host‐related (age, obesity) or linked to the severity of cirrhosis (thrombopenia), and the European PAGE‐B score was the most accurate risk score.