Journal of Clinical Virology最新文献

{"title":"Universal screening for congenital Cytomegalovirus infection using saliva from the neonate","authors":"Gabriele Halwachs-Baumann ,&nbsp;Oliver Wagner ,&nbsp;Yarub Salaheddin ,&nbsp;Eveline Ziebermayr ,&nbsp;Lukas Angleitner-Boubenizek ,&nbsp;Georg Grüßenberger ,&nbsp;Ulla Folger-Buchegger","doi":"10.1016/j.jcv.2025.105800","DOIUrl":"10.1016/j.jcv.2025.105800","url":null,"abstract":"<div><h3>Background</h3><div>Congenital Cytomegalovirus infection (cCMV) is the most common intrauterine infection in developed countries. The diagnostic gold standard is detection of CMV in neonatal urine. Considering difficulties in urine sample collection, saliva is an alternative specimen providing supportive material for early diagnosis and timely intervention.</div></div><div><h3>Objectives</h3><div>Aim of this study was to evaluate a universal screening program using saliva as target specimen, and urine as confirmatory material.</div></div><div><h3>Results</h3><div>Between May 2019 and November 2024, 5168 newborns were screened for CMV shedding in saliva, 45 neonates were tested positive. From 44 neonates a urine sample was examined. Twelve out of forty-four neonates had concordant results (prevalence = 0,232 %) with five newborns showing CMV related symptoms. In saliva, the difference between the Ct-value of the cCMV negative and the cCMV positive group was significant (38.59 vs. 28.56, p-value &lt; 0.0001). At a Ct-value cut-off of 38.8 sensitivity was 100 %, specificity 53.1 %, positive predictive value 44 %, and negative predictive value 100 %. ROC analysis yielded an AUC value of 0.930. The mean virus load in urine was 31,266,663 copies/ml.</div></div><div><h3>Discussion</h3><div>This study reports a prevalence of 0,232 % for cCMV infection in the catchment area of the hospital Steyr. PCR based CMV detection in saliva is a good screening tool, but one must be aware of false positive results, arising from possible contamination. In our cohort CMV positive vaginal or cervical secretion seems more likely being the source of contamination than CMV positive breast milk. The high false positive rate in saliva makes confirmatory testing in urine samples mandatory.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"178 ","pages":"Article 105800"},"PeriodicalIF":4.0,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human cytomegalovirus (HCMV) glycoprotein M occurs in three distinct genotypes in laboratory strains and clinical isolates","authors":"Alia Al-Alfard ,&nbsp;Zahrah Buhamad ,&nbsp;Julia Duffey ,&nbsp;Simon Lovell ,&nbsp;Paul Klapper ,&nbsp;Pamela Vallely","doi":"10.1016/j.jcv.2025.105799","DOIUrl":"10.1016/j.jcv.2025.105799","url":null,"abstract":"<div><h3>Background</h3><div>HCMV carries virus-encoded envelope glycoproteins important for viral attachment, entry into host cells and replication. These glycoproteins have polymorphic features resulting in distinct genotypes some of which have been associated with disease outcome. Glycoprotein complex II comprises glycoproteins M (gM) and N (gN) and is essential for viral replication. Glycoprotein N is highly polymorphic while gM is highly conserved. The existence of distinct gM genotypes has not previously been reported.</div></div><div><h3>Study design</h3><div>PCR amplification of the entire gM gene (1298 bp) was carried out on five HCMV laboratory strains (AD169, Towne, Davis, Toledo, Merlin) and ten clinical isolates. PCR product was sequenced and nucleotide and aminoacid phylogenetic trees constructed for these samples and for an additional 287 HCMV gM sequences obtained from NCBI database. The hydrophobicity of the predicted protein sequences was compared.</div></div><div><h3>Results</h3><div>Three distinct genotypes were identified (gM1, gM2 and gM3) with every sequence aligning with one genotype, suggesting they are stable polymorphisms rather than random nucleotide substitutions. Aminoacid translation of the nucleotide sequences merged gM1 and gM2, but gM3 remained as a distinct and separate type. The aminoacid substitutions led to changes in the hydrophobicity of the 3 glycoprotein types particularly between gM3 and the other two types.</div></div><div><h3>Conclusions</h3><div>Glycoprotein M is highly conserved, but we have identified three distinct genotypes, arising from variability in a small region of the genome. These changes altered the predicted hydrophobicity of the glycoprotein potentially altering the conformational structure of the glycoprotein and affecting its function <em>in vivo</em>.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"178 ","pages":"Article 105799"},"PeriodicalIF":4.0,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the clinical and molecular epidemiology of an infections outbreak of human parvovirus B19 in France, 2023–2024","authors":"Elisa Creuzet ,&nbsp;Wendy Pulby ,&nbsp;Christine Archimbaud ,&nbsp;Amélie Brebion ,&nbsp;Hélène Chabrolles ,&nbsp;Audrey Mirand ,&nbsp;Ophélie Perruche ,&nbsp;Mathilde Picard ,&nbsp;Christel Regagnon ,&nbsp;Céline Lambert ,&nbsp;Siméon Bakyono ,&nbsp;Jean-Luc Bailly ,&nbsp;Maxime Bisseux ,&nbsp;Cécile Henquell","doi":"10.1016/j.jcv.2025.105798","DOIUrl":"10.1016/j.jcv.2025.105798","url":null,"abstract":"<div><h3>Background</h3><div>The human parvovirus B19 (B19V) infections cycle occurs in 3- to 4-year periods and is responsible for benign childhood erythema infectiosum. It is also associated with transient aplastic crisis in patients with underlying hemolytic diseases and with severe fetal sometimes fatal infection. This study investigated the epidemiological, clinical and molecular characteristics of an unusually large 2023–2024 outbreak of B19V.</div></div><div><h3>Methods</h3><div>Laboratory-confirmed cases were retrospectively and prospectively recorded at the Clermont-Ferrand University Hospital, France, between January, 2018 and November, 2023 and between December 2023 and May 2024 (2023/2024), respectively. Demographical and clinical data were investigated for the 2023/2024 period. Subgenome sequences (2690 nt) were obtained by next generation sequencing for virus genotyping and temporal molecular analysis.</div></div><div><h3>Results</h3><div>The positive rate of B19V positive laboratory-confirmed cases was seven times higher between December 2023 and May 2024 than in the previous 5-year period (14.6 % vs 2.1 %, p &lt; 0.001). No atypical clinical presentation or increased pathogenicity were observed, but this large outbreak resulted in a higher number of severe infections in pregnant women (8/16, 50.0 % of fetal complications) and those with chronic anemia. Phylogenetic analysis revealed that the 2023/2024 outbreak in France and Europe was mainly driven by a pre-existing lineage of B19V 1a subgenotype that emerged in 2017 (95 % highest posterior density interval: 2000–2018).</div></div><div><h3>Conclusions</h3><div>The recent epidemic of B19V infections re-illustrates the immunity gap of the post-pandemic COVID-19 pandemic. This highlight the impact of any outbreak on at-risk population and the need for a more global and genomic surveillance.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"178 ","pages":"Article 105798"},"PeriodicalIF":4.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of influenza A(H1N1)pdm09 6B.1A.5a.2a and 6B.1A.5a.2a.1 subclades leading to subtyping failure in a commercial molecular assay","authors":"Bosung Park,&nbsp;Eun Jeong Won,&nbsp;Heungsup Sung,&nbsp;Mi-Na Kim","doi":"10.1016/j.jcv.2025.105797","DOIUrl":"10.1016/j.jcv.2025.105797","url":null,"abstract":"<div><h3>Background</h3><div>During the 2023–2024 and early 2024–2025 influenza seasons, several influenza A-positive specimens in our laboratory failed subtyping for H1, H1pdm09, and H3 using the Allplex Respiratory Panel 1 (Allplex RP1) (Seegene Inc.). This study aimed to identify the cause of these subtyping failures.</div></div><div><h3>Materials and methods</h3><div>Between August 2023 and December 2024, 23 nasopharyngeal specimens tested positive for influenza A but were unsubtypeable for H1, H1pdm09, and H3. Confirmatory testing by the manufacturer included target-specific PCR for the M and HA genes, followed by sequencing to determine subclades.</div></div><div><h3>Results</h3><div>Among the 23 unsubtypeable specimens, 22 yielded PCR products for sequencing. Of these, 21 belonged to subclade 6B.1A.5a.2a.1 and one to 6B.1A.5a.2a. Sequence analysis revealed mismatches in the H1pdm09 primer/probe-binding regions of Allplex RP1, explaining the subtyping failures. Despite testing negative for H1pdm09 in Allplex RP1, sequencing confirmed their classification as H1N1pdm09 subclades with HA gene mutations.</div></div><div><h3>Conclusions</h3><div>Subclades 6B.1A.5a.2a.1 and 6B.1A.5a.2a harbour mutations that contributed to subtyping failures in some specimens tested with a commercial assay. While unsubtypeable influenza A results often raise concerns about emerging strains, sequencing confirmed that all unsubtypeable specimens tested with Allplex RP1 belonged to H1N1pdm09 within recognised subclades. Thus, such subtyping failures in this assay do not necessarily indicate a novel or zoonotic virus, though genomic surveillance remains essential.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"178 ","pages":"Article 105797"},"PeriodicalIF":4.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained circulation of enterovirus D68 in Europe in 2023 and the continued evolution of enterovirus D68 B3-lineages associated with distinct amino acid substitutions in VP1 protein","authors":"Aurora Hirvonen ,&nbsp;Caroline Klint Johannesen ,&nbsp;Peter Simmonds ,&nbsp;Thea K Fischer ,&nbsp;Heli Harvala ,&nbsp;Kimberley S.M. Benschop ,&nbsp;on behalf of ENPEN study collaborators","doi":"10.1016/j.jcv.2025.105785","DOIUrl":"10.1016/j.jcv.2025.105785","url":null,"abstract":"<div><h3>Background</h3><div>Enterovirus D68 (EV-D68) causes respiratory disease ranging from mild to severe and in rare cases a paralytic syndrome, called acute flaccid myelitis (AFM). Since the global EV-D68 outbreak in 2014, the virus has mainly circulated in biennial epidemic cycles with peaks detected during even years. However, following the COVID-19 pandemic, the seasonal pattern of EV-D68 has been characterized by large yearly upsurges. Here, we describe the circulation of EV-D68 in Europe in 2023 and track its genetic evolution.</div></div><div><h3>Study design</h3><div>Data was compiled from members of the European Non-Polio Network (ENPEN). This included monthly data on the total number of EV samples tested, EV positive samples, EV-D68 positive samples and cases, and other EV positive samples detected in 2023. Information on sample types and surveillance system was recorded. Sequence data from the VP1 gene was used for phylogenetic and amino acid sequence analysis.</div></div><div><h3>Results</h3><div>EV was detected in 13585 out of 203622 diagnostic samples tested (6.7%), of which 402 (3.0%) were determined as EV-D68, representing 386 cases. EV-D68 infections peaked in October 2023 (136/386; 35.2%). 267/386 (69.2%) of EV-D68 cases were captured through clinical EV surveillance, almost all of which (202/204 of positive samples with sample type information) were detected in respiratory specimens. Phylogenetic analysis performed on 99 VP1 sequences revealed a distinct B3-derived lineage with a previously undescribed residue change, D554E, in Europe.</div></div><div><h3>Conclusions</h3><div>The study documents sustained circulation of EV-D68 in Europe in 2023, the evolution of B3-derived lineages, and appearance of previously undescribed amino acid substitutions in Europe. This stresses the need for continuous EV-D68 surveillance and harmonization of EV-D68 detection practices towards better data comparability across countries.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"178 ","pages":"Article 105785"},"PeriodicalIF":4.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility and performance evaluations of Alinity m quantitative NAT for HBV and HCV","authors":"Sana Sajid,&nbsp;Zaira Rehman,&nbsp;Fouzia Naseer,&nbsp;Sana Faisal Raza,&nbsp;Javeria Aijaz","doi":"10.1016/j.jcv.2025.105784","DOIUrl":"10.1016/j.jcv.2025.105784","url":null,"abstract":"<div><h3>Background</h3><div>Rapid and accurate testing for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) is essential for management of these infections. Selecting the most appropriate testing methodology entails feasibility considerations of cost and throughput in addition to performance evaluations.</div></div><div><h3>Objective</h3><div>In this study, we determined the feasibility and analytical performance of Alinity m in comparison with Roche Cobas 6800 for both assays according to College of American Pathologists (CAP) standards, and Clinical and Laboratory Standards Institute (CLSI) guidelines.</div></div><div><h3>Results</h3><div>Unit costs remain relatively stable until around a monthly test volume of 1200. Below this volume, cost escalation pattern varies, such that at 60 tests/month, unit costs increase 9-fold for tests on Roche Cobas 6800, but relatively modestly (2.5-fold) for tests on Alinity m. The 24-h throughput of Alinity m, however, is lower than that of Roche Cobas 6800. The overall concordance between the Alinity m and Cobas 6800 was 97.5 % (39/40) for HBV and 87.5 % (35/40) for HCV. The reportable range was from 1.765 to 8.460 log IU/mL (58.2 to 2.8 × 10⁸ IU/mL) for HBV, and from 1.975 to 7.250 log IU/mL (94.4 to 1.7 × 10⁷ IU/mL) for HCV. The complete reportable range remained undetermined on account of non-availability of extreme viral titer samples. Both intra and inter-run precision, as evaluated by SD falling within the manufacturer-reported, were within acceptable limits. No evidence of cross-contamination was found.</div></div><div><h3>Conclusion</h3><div>Alinity m demonstrated acceptable performance in comparison with Roche Cobas 6800 for HBV and HCV NAT. Additionally, it demonstrated suitability for lower throughput labs in terms of unit test costs.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105784"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular epidemiology of Kyasanur forest disease employing ONT-NGS a field forward sequencing","authors":"Shashi Sharma ,&nbsp;Pooja Yadav ,&nbsp;Paban Kumar Dash,&nbsp;Suman Dhankher","doi":"10.1016/j.jcv.2025.105783","DOIUrl":"10.1016/j.jcv.2025.105783","url":null,"abstract":"<div><div>The future of infectious agent detection and molecular characterization lies in field-forward, on-site strategies. The lack of genomic information for recently circulating Kyasanur Forest Disease virus strains is critical. Kyasanur Forest Virus Disease virus PCR-positive samples from 2018 to 2020 were selected for sequencing. Detailed molecular phylogenetic analyses were performed. In this study, we deciphered KFDV whole genomes using the ONT-NGS technique to analyze targeted KFD surveillance from 2018–2020. This study is the first to report recently circulating KFDV strains employing a simple on-site field-forward approach for viral surveillance. Altogether, 19 KFDV genomes were sequenced, and 28 non-synonymous variants were detected in the viral strains circulating from 2018–2020 in the Shivamogga district of Karnataka state in India. The prevailing Variant was detected in more than 10 changes in 80 % of the samples in the viral envelope protein. Recently, circulating KFDV has been the predominant lineage over the past years. India reports seasonal outbreaks almost every year from the Karnataka state of the KFD. The genomic sequences deciphered here belong to the period (2018–2020) that covers the KFDV sequences as the first information. This will contribute to the development and revisiting of diagnostic and vaccine strategies.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105783"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleocapsid-directed antibody testing is unsuitable to estimate hybrid immunity against SARS-CoV-2, a longitudinal cross-border study in the Meuse-Rhine Euroregion","authors":"D.A.T. Hanssen ,&nbsp;C.J.A. van Bilsen ,&nbsp;C.D.J. den Heijer ,&nbsp;C. Stabourlos ,&nbsp;C.P.B. Moonen ,&nbsp;R. de Vries ,&nbsp;S. Brinkhues ,&nbsp;D. Philipssen ,&nbsp;B.A.M. van der Zanden ,&nbsp;N.H.T.M. Dukers-Muijrers ,&nbsp;C.J.P.A. Hoebe ,&nbsp;P.H.M. Savelkoul ,&nbsp;I.H.M. van Loo","doi":"10.1016/j.jcv.2025.105780","DOIUrl":"10.1016/j.jcv.2025.105780","url":null,"abstract":"<div><h3>Introduction</h3><div>Understanding immunity from previous natural SARS-CoV-2 infection is important for booster vaccination strategies. A longitudinal study conducted in 2021 within the Meuse-Rhine Euroregion, bordering the Netherlands, Belgium, and Germany, aimed to assess seroprevalence of spike-directed (anti-S) and nucleocapsid-directed (anti-N) antibodies to demonstrate immunity as a result of both vaccination and natural infection (hybrid immunity), and to evaluate the dynamics of the anti-N response.</div></div><div><h3>Materials and methods</h3><div>Questionnaires and self-finger-prick blood samples from 3110 participants were collected at two time points: weeks 22–29 (June–July, round 1) and weeks 40–45 (October–November, round 2) of 2021. Individuals with anti-S antibodies were additionally tested for anti-N antibodies.</div></div><div><h3>Results</h3><div>In total, 4366 samples tested positive for anti-S; n = 1291 for round 1 and n = 3075 for round 2. Of these, 10.1 % of Dutch (32/316), 3.1 % of Belgian (9/294), and 2.8 % of German participants (13/466) were anti-N positive in round 1 (p &lt; 0.001). In round 2, this was 4.6 % (69/1510), 3.3 % (20/607), and 1.5 % (14/912), respectively (p &lt; 0.001). In 45.1 % (23/51) of anti-N positive participants in round 1, the result reversed to negative in round 2. In 42.1 % (16/38) of anti-N positive participants with a self-reported positive PCR result, anti-N reversed to negative in round 2.</div></div><div><h3>Conclusion</h3><div>Variations in anti-N seroprevalence across EMR countries may reflect differences in vaccination campaign enrollment. Over 40 % of participants experienced seroreversion of anti-N within six months, indicating anti-N testing is unsuitable for diagnosing past infection or estimating hybrid immunity within a population. However, anti-N testing may be used as a proxy for increased circulation of SARS-CoV-2 in a population.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105780"},"PeriodicalIF":4.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of metformin on HBV replication: No evidence of suppression in vitro","authors":"Cyrus Hawkins ,&nbsp;Elizabeth Waddilove ,&nbsp;Philippa C. Matthews ,&nbsp;Marion Delphin","doi":"10.1016/j.jcv.2025.105781","DOIUrl":"10.1016/j.jcv.2025.105781","url":null,"abstract":"<div><h3>Background</h3><div>Outcomes of chronic Hepatitis B (CHB) infection have been increasingly associated with various metabolic syndromes, including metabolic-dysfunction associated steatotic liver disease (MASLD), with a potential for impact on liver disease progression. There is some evidence that metformin, a widely used anti-diabetic drug, may reduce hepatocellular carcinoma (HCC) incidence in people living with Hepatitis B Virus (HBV), but with little to no evidence of impact on the virus itself <em>in vivo</em>. However, previous <em>in vitro</em> studies suggest metformin may have a direct impact on HBV replication, although the mechanism remains unclear.</div></div><div><h3>Objectives</h3><div>We aimed to investigate the impact of metformin on HBV replication <em>in vitro</em>.</div></div><div><h3>Study design</h3><div>Hepatocyte cell lines constitutively expressing HBV (HepAD38) were treated once or thrice with escalating doses of metformin, using lamivudine and water as controls. We monitored cellular cytotoxicity as well as HBV biomarkers (HBeAg, HBsAg, HBV DNA and RNA) throughout the assay.</div></div><div><h3>Results</h3><div>We did not observe any impact of metformin on HBV replication after a single dose or three repeated treatments.</div></div><div><h3>Conclusions</h3><div>In HepAD38 cells, HBV replication is not impacted by metformin treatment. This contrasts with prior <em>in vitro</em> data but is in line with clinical evidence that suggests metformin acts through an influence on liver disease progression rather than a direct antiviral impact on HBV itself.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105781"},"PeriodicalIF":4.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-year hearing outcomes in infants with congenital cytomegalovirus disease treated with oral valganciclovir: Interim results of a six-year follow-up study in Japan","authors":"Ichiro Morioka ,&nbsp;Yasumasa Kakei ,&nbsp;Takumi Imai ,&nbsp;Kazumichi Fujioka ,&nbsp;Naoto Takahashi ,&nbsp;Tetsushi Yoshikawa ,&nbsp;Hiroyuki Moriuchi ,&nbsp;Yoshinori Ito ,&nbsp;Akira Oka ,&nbsp;for the Japanese Congenital Cytomegalovirus Study Group","doi":"10.1016/j.jcv.2025.105778","DOIUrl":"10.1016/j.jcv.2025.105778","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the long-term hearing outcomes of infants with symptomatic congenital cytomegalovirus (CMV) disease who received 16 mg/kg of oral valganciclovir (VGCV) twice daily for six months.</div></div><div><h3>Study design</h3><div>We have currently performed a long-term extension study of an investigator-initiated, single-arm, prospective, multicenter clinical trial, in which 24 infants were treated with VGCV. Hearing outcomes up to three years after treatment initiation were described and the longitudinal changes in the proportion of \"Improved hearing\" were analyzed using logistic regression. The factors associated with these outcomes were explored. Adverse events that occurred after the completion of the administration period were assessed.</div></div><div><h3>Results</h3><div>At 3 years, among 48 ears from 24 infants, the number of \"improved hearing,\" which was 19 (40.0 %) ears at 6 months, increased to 27 (56.3 %) ears (p = 0.032). When including “maintaining normal hearing” or “maintaining normal hearing or the same degree of hearing impairment”, the corresponding numbers were observed in 35 (72.9 %) and 45 (93.7 %) ears at 3 years, which were 25 (52.5 %) and 45 (93.7 %) ears at 6 months, respectively. Infants with milder hearing impairment at baseline showed high likelihood of hearing improvement (p for trend = 0.018 by the regression analysis). No adverse events were observed after completion of the administration period.</div></div><div><h3>Conclusion</h3><div>Oral administration of VGCV demonstrated efficacy in improving hearing in infants with symptomatic congenital CMV disease at 3 years of age. These results suggest that the treatment response may be particularly favorable in patients with a lower initial degree of hearing impairment.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105778"},"PeriodicalIF":4.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}