Genetic and biological properties of H9N2 avian influenza viruses isolated in central China from2020 to 2022

The H9N2 subtype of avian influenza virus(AIV)is widely prevalent in poultry and wild birds globally,and has become the predominant subtype circulating in poultry in China.The H9N2 AIV can directly or indirectly(by serving as a"donor virus")infect humans,posing a significant threat to public health.Currently,there is a lack of in-depth research on the prevalence of H9N2 viruses in Shanxi Province,central China.In this study,we isolated 14 H9N2 AIVs from October 2020 to April 2022 in Shanxi Province,and genetic analysis revealed that these viruses belonged to 7 different genotypes.Our study on animals revealed that the H9N2 strains we identified displayed high transmission efficiency among chicken populations,and exhibited diverse replication abilities within these birds.These viruses could replicate efficiently in the lungs of mice,with one strain also demonstrating the capacity to reproduce in organs like the brain and kidneys.At the cellular level,the replication ability of different H9N2 strains was evaluated using plaque formation assays and multi-step growth curve assays,revealing significant differences in the replication and proliferation efficiency of the various H9N2 viruses at the cellular level.The antigenicity analysis suggested that these isolates could be classified into 2 separate antigenic clusters.Our research provides crucial data to help understand the prevalence and biological characteristics of H9N2 AIVs in central China.It also highlights the necessity of enhancing the surveillance of H9N2 AIVs.

Substitutions of stem-loop subdomains in internal ribosome entry site of Senecavirus A:Impacts on rescue of sequence-modifying viruses

Senecavirus A(SVA)has a positive-sense,single-stranded RNA genome.Its 5´untranslated region harbors an internal ribosome entry site(IRES),comprising 10 larger or smaller stem-loop structures(including a pseudoknot)that have been demonstrated to be well conserved.However,it is still unclear whether each stem-loop subdomain,such as a single stem or loop,is also highly conserved.To clarify this issue in the present study,a set of 29 SVA cDNA clones were constructed by site-directed mutagenesis(SDM)on the IRES.The SDM-modified scenarios included:(1)stem-formed complementary sequences exchanging with each other;(2)loop transversion;(3)loop transition;and(4)point mutations.All cDNA clones were separately transfected into cells for rescuing viable viruses,whereas only four SVAs of interest could be recovered,and were genetically stable during 20 passages.One progeny grew significantly slower than the other three did.The dual-luciferase reporter assay showed that none of the SDM-modified IRESes significantly inhibited the IRES activity.Our previous study indicated that a single motif from any of the ten stem structures,if completely mutated,would cause the failure of virus recovery.Interestingly,our present study revealed three stem structures,whose individual complementary sequences could exchange with each other to rescue sequence-modifying SVAs.Moreover,one apical loop was demonstrated to have the ability to tolerate its own full-length transition,also having no impact on the recovery of sequence-modifying SVA.The present study suggested that not every stem-loop structure was strictly conserved in its conformation,while the full-length IRES itself was well conserved.This provides a new research direction on interaction between the IRES and many factors.

Identification of novel mammalian viruses in tree shrews(Tupaia belangeri chinensis)

The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.

Surveillance of arthropod-borne viruses in Benin,West Africa 2020–2021:detection of dengue virus 3 in Aedes aegypti(Diptera:Culicidae)

Dear Editor,Dengue virus(DENV,family Flaviviridae,genus Flavivirus)serotypes 1 to 4(DENV-1,-2,-3,and-4)are responsible for more than 100 million infections per year worldwide.Symptoms of DENV infection can be diverse,reaching from an acute febrile illness to the more severe,sometimes fatal dengue haemorrhagic fever/dengue shock syndrome.

Progress in oncolytic viruses modified with nanomaterials for intravenous application

In oncolytic virus(OV)therapy,a critical component of tumor immunotherapy,viruses selectively infect,replicate within,and eventually destroy tumor cells.Simultaneously,this therapy activates immune responses and mobilizes immune cells,thereby eliminating residual or distant cancer cells.However,because of OVs’high immunogenicity and immune clearance during circulation,their clinical applications are currently limited to intratumoral injections,and their use is severely restricted.In recent years,numerous studies have used nanomaterials to modify OVs to decrease virulence and increase safety for intravenous injection.The most commonly used nanomaterials for modifying OVs are liposomes,polymers,and albumin,because of their biosafety,practicability,and effectiveness.The aim of this review is to summarize progress in the use of these nanomaterials in preclinical experiments to modify OVs and to discuss the challenges encountered from basic research to clinical application.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Rapid inactivation of human respiratory RNA viruses by deep ultraviolet irradiation from light-emitting diodes on a high-temperatureannealed AlN/Sapphire template

Efficient and eco-friendly disinfection of air-borne human respiratory RNA viruses is pursued in both public environment and portable usage.The AlGaN-based deep ultraviolet(DUV)light-emission diode(LED)has high practical potentials because of its advantages of variable wavelength,rapid sterilization,environmental protection,and miniaturization.Therefore,whether the emission wavelength has effects on the disinfection as well as whether the device is feasible to sterilize various respiratory RNA viruses under portable conditions is crucial.Here,we fabricate AlGaN-based DUV LEDs with different wavelength on high-temperature-annealed(HTA)AlN/Sapphire templates and investigate the inactivation effects for several respiratory RNA viruses.The AlN/AlGaN superlattices are employed between the template and upper n-AlGaN to release the strong compressive stress(SCS),improving the crystal quality and interface roughness.DUV LEDs with the wavelength of 256,265,and 278 nm,corresponding to the light output power of 6.8,9.6,and 12.5 mW,are realized,among which the 256 nm-LED shows the most potent inactivation effect in human respiratory RNA viruses,including SARS-CoV-2,influenza A virus(IAV),and human parainfluenza virus(HPIV),at a similar light power density(LPD)of~0.8 mW/cm2 for 10 s.These results will contribute to the advanced DUV LED application of disinfecting viruses with high potency and broad spectrum in a portable and eco-friendly use.

Phylogenetic and epidemiological characteristics of H9N2 avian influenza viruses in Shandong Province, China from 2019 to 2021

H9N2 avian influenza virus(AIV) has widely circulated in poultry worldwide and sporadic infections in humans and mammals. During our surveillance of chicken from 2019 to 2021 in Shandong Province, China, we isolated 11 H9N2AIVs. Phylogenetic analyses showed that the eight gene segments of the 11 isolates were closely related to several sublineages of Eurasian lineage: BJ/94-like clades(HA and NA genes), G1-like clades(PB2 and M genes), and SH/F/98-like clades(PB1, PA, NP and NS genes). The isolates showed mutation sites that preferentially bind to humanlike receptors(HA) and mammalian fitness sites(PB2, PB1 and PA), as well as mutations in antigen and drug resistance sites. Moreover, studies with mice revealed four isolates with varying levels of pathogenicity. The average antibody titer of the H9N2 AIVs was 8.60 log2. Based on our results, the epidemiological surveillance of H9N2 AIVs should be strengthened.

Genetic Diversity Analysis of Badnaviruses Infecting Banana in Burkina Faso

Badnaviruses are serious plant pararetroviruses affecting banana and causes serious economic losses to banana production worldwide. This study aims to examine the variability of BSV and SCBV nature infecting banana in Burkina Faso. Polymerase Chain Reaction (PCR) used the Badna FP/RP specific primers for the RT/RNase H regions present in badnaviruses. The PCR yielded about 579 bp amplicons from banana infected by BSV and SCBV. The 38 BSV isolates recorded low nucleotide identity ranging from 58.9% - 98.1%. Based on percentage nucleotide sequence identity and phylogenetic analyse, BSV isolates were categorized into four groups: 1, 2, 3 and 4. Group 4 shared 76.9% - 100% identity with BSOL species. However, Groups 1 and 3 recorded a low identity ranging, from 76.8% - 79.2%, 68.8% - 79.7% with BSCV, and 72.8% - 79.0% between Group 2 and BSOLV. Groups 1, 2 and 3 were assigned to a potentially new BSV species. The two SCBV isolates recorded a low nucleotide identity of 68% among themselves indicating high diversity. In addition, SCBV_Cd and SCBV_CE showed high nucleotide identity 91.3% and 58.7% with SCBV_C and SCBV, when they were compared to all published SCBV genotypes. In addition, phylogenetic analysis revealed the segregation of SCBV isolates into two genotypes, SCBV_Cd in C and SCBV_CE segregated in a new genotype namely Z. Recombination analyses showed weak signatures of recombination among some of the BSV and SCBV sequences.

Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.

CRISPR/CasRx-mediated resistance to Soybean mosaic virus in soybean

Soybean mosaic virus(SMV),an RNA virus,is the most common and destructive pathogenic virus in soybean fields.The newly developed CRISPR/Cas immune system has provided a novel strategy for improving plant resistance to viruses;hence,this study aimed to engineer SMV resistance in soybean using this system.Specifically,multiple sgRNAs were designed to target positive-and/or negative-sense strands of the SMV HC-Pro gene.Subsequently,the corresponding CRISPR/CasRx vectors were constructed and transformed into soybeans.After inoculation with SMV,39.02%,35.77%,and 18.70%of T_(1)plants were confirmed to be highly resistant(HR),resistant(R),and mildly resistant(MR)to SMV,respectively,whereas only 6.50%were identified as susceptible(S).Additionally,qRT-PCR and DAS-ELISA showed that,both at 15 and 30 d post-inoculation(dpi),SMV accumulation significantly decreased or was even undetectable in HR and R plants,followed by MR and S plants.Additionally,the expression level of the CasRx gene varied in almost all T_(1)plants with different resistance level,both at 15 and 30 dpi.Furthermore,when SMV resistance was evaluated in the T_(2)generation,the results were similar to those recorded for the T_(1)generation.These findings provide new insights into the application of the CRISPR/CasRx system for soybean improvement and offer a promising alternative strategy for breeding for resistance to biotic stress that will contribute to the development of SMV-immune soybean germplasm to accelerate progress towards greater soybean crop productivity.

Efficacy and mechanisms of Traditional Chinese Medicine prevention and treatment for respiratory viruses

Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world's public health and human life safety.Commonly used antiviral drugs have obvious side effects and a narrow scope of application.Respiratory viruses are susceptible to infection,mutation,and prevalence,which also pose challenges to traditional antiviral drugs and vaccine development.Traditional Chinese Medicine(TCM)has a long history of treating infectious diseases,with many herbs and compounds.Its multi-component,multi-target and multi-path characteristics have made it have great advantages and potential in the development of new anti-respiratory virus drugs.This review summarized TCM for the prevention and treatment of common respiratory viruses,and provided new strategies for the research and development of new TCM antiviral drugs and for responding to infectious respiratory virus diseases.

56 Years of the Marburg Virus—A Review of Therapeutics

Background: The Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD). This filovirus first appeared in 1967 and has since caused several outbreaks with case fatality rates between 23% and 90%. The earliest cases of MVD are thought to be caused by exposure to an infected animal, either a reservoir host (some bat species, e.g., Rousettus aegyptiacus) or a spill-over host, such as non-human primates. The virus is spread between people by direct contact with blood or other bodily fluids (including saliva, sweat, faeces, urine, tears, and breast milk) from infected individuals. Despite the high fatality rate, the Marburg virus has no vaccine or drug treatment. Recent outbreaks of the virus in 2023 in Tanzania and Equatorial Guinea have reignited the need to develop effective therapeutics, especially in the wake of the COVID-19 pandemic. Purpose: This review seeks to highlight the drug discovery efforts aimed at developing vaccines or possible treatments as potential therapeutics. Several existing antiviral agents are being probed, and vaccines are in pre-clinical and clinical stages. Natural products are also an important source of possible drugs or lead compounds and when coupled with computational techniques, these strategies offer possible therapeutics for the Marburg virus, especially in Africa, which has a high disease burden. Methods: Using the search engines Google Scholar and PubMed;keywords e.g. Marburg virus, Marburg treatments, Marburg virus drug discovery were utilized. Several results were yielded, and articles published in recent years were accepted into the final list.Results and Conclusion: This study shows there is a growing interest in therapeutics for the Marburg virus, especially with the recent outbreaks and pandemic preparedness. Initiatives that to support vaccine development and access like the MARVAC consort time are critical to fighting this public health threat.

Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.

Bat pluripotent stem cells reveal unusual entanglement between host and viruses

Bats are distinctive among mammals due to their ability to fly,use laryngeal echolocation,and tolerate viruses.However,there are currently no reliable cellular models for studying bat biology or their response to viral infections.Here,we created induced pluripotent stem cells(iPSCs)from two species of bats:the wild greater horseshoe bat(Rhinolophus ferrumequinum)and the greater mouse-eared bat(Myotis myotis).The iPSCs from both bat species showed similar characteristics and had a gene expression profile resembling that of cells attacked by viruses.They also had a high number of endogenous viral sequences,particularly retroviruses.These results suggest that bats have evolved mechanisms to tolerate a large load of viral sequences and may have a more intertwined relationship with viruses than previously thought.Further study of bat iPSCs and their differentiated progeny will provide insights into bat biology,virus host relationships,and the molecular basis of bats'special traits.

Bat pluripotent stem cells reveal unusual entanglement between host and viruses

Bats are distinctive among mammals due to their ability to fly, use laryngeal echolocation, and tolerate viruses. However,there are currently no reliable cellular models for studying bat biology or their response to viral infections. Here, we createdinduced pluripotent stem cells (iPSCs) from two species of bats: the wild greater horseshoe bat (Rhinolophus ferrumequinum) andthe greater mouse-eared bat (Myotis myotis). The iPSCs from both bat species showed similar characteristics and had a geneexpression profile resembling that of cells attacked by viruses. They also had a high number of endogenous viral sequences,particularly retroviruses. These results suggest that bats have evolved mechanisms to tolerate a large load of viral sequences andmay have a more intertwined relationship with viruses than previously thought. Further study of bat iPSCs and their differentiatedprogeny will provide insights into bat biology, virus host relationships, and the molecular basis of bats' special traits.

Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

Development of a stable attenuated double-mutant of tobacco mosaic virus for cross-protection

Tobacco(Nicotiana tabacum)and tomato(Solanum lycopersicum)are two major economic crops in China.Tobacco mosaic virus(TMV;genus Tobamovirus)is the most prevalent virus infecting both crops.Currently,some widely cultivated tobacco and tomato cultivars are susceptible to TMV and there is no effective strategy to control this virus.Cross-protection can be a safe and environmentally friendly strategy to prevent viral diseases.However,stable attenuated TMV mutants are scarce.In this study,we found that the substitutions in the replicase p126,arginine at position 196(R^(196))with aspartic acid(D),glutamic acid at position 614(E^(614))with glycine(G),serine at position 643(S^(643))with phenylalanine(F),or D at position 730(D^(730))with S,significantly reduced the virulence and replication of TMV.However,only the mutation of S^(643) to F reduced the RNA silencing suppression activity of TMV p126.A double-mutant TMV-E614G-S643F induced no visible symptom and was genetically stable through six successive passages in tobacco plants.Furthermore,our results showed that TMV-E614G-S643F double-mutant could provide effective protection against the wild-type TMV infection in tobacco and tomato plants.This study reports a promising mild mutant for cross-protection to control TMV in tobacco and tomato plants.

Management of autoimmune hepatitis induced by hepatitis delta virus

Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhosis,fulminant hepatitis,and hepatocellular carcinoma,being the most common.Over the past few decades,a correlation between viral hepatitis and autoimmune diseases has been reported.Furthermore,autoantibodies have been detected in the serum of patients co-infected with HBV/HDV,and autoimmune features have been reported.However,to date,very few cases of clinically significant autoimmune hepatitis(AIH)have been reported in patients with HDV infection,mainly in those who have received treatment with pegylated interferon.Interestingly,there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants.Consequently,several questions remain unanswered with the challenge to distinguish whether it is autoimmune or“autoimmune-like”hepatitis being the most crucial.Second,it remains uncertain whether autoimmunity is induced by HBV or delta virus.Finally,we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon.These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV,such as Bulevirtide or immu-nosuppressive drugs,are more appropriate for the management of patients with HDV and AIH.