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Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p

Objective A single study conducted about three decades ago on hepatitis D virus (HDV) infection among Baka pygmies in Cameroon reported a very high anti-HDV antibodies prevalence of 46%, but HDV genetic diversity has not been studied in this population. The genetic diversity of strains from endemic ancient populations may help to understand the origin and evolutionary history of viruses. This study aimed to investigate the HDV seroprevalence and the genetic diversity in three remote Cameroonian Pygmies with chronic HBV infection. Results An unusually high 69% (36/52) level of HDV infection was found among HBsAg-positive pygmies in Cameroon. HDV RNA was detected and sequenced in 38.8% (14/36). The phylogenetic analysis revealed that 9/14 strains (64.3%) were identified and classified as genotype 1 (HDV-1) and 5/14 (35.6%) as genotype 7 (HDV-7), respectively with a bootstrap value of 100%. The further analysis showed the co-circulation of highly diverse HDV genotypes HDV-1 and HDV-7 in this population. These results highlight the endemicity of HDV infection in Central Africa. The highly diverse HDV-1 and HDV-7 in pygmies suggest an African origin of HDV. However, further studies are needed with larger sample size.

Background & AimsThe international incidence of Hepatitis Delta Virus (HDV) is challenging to accurately estimate due to limited testing and lack of active surveillance for this rare infectious disease. These limitations prevent the detection of low-level and/or geographically dispersed changes in the incidence of HDV diagnoses. A study was designed to enable international active tracking and analyses of HDV epidemiology by aggregating international HDV and Hepatitis B Virus (HBV) diagnoses datasets.MethodsPublicly accessible datasets containing yearly incidence for HDV and HBV diagnoses were mined from government publications for Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Finland, Germany, Macao, Netherlands, New Zealand, Norway, Sweden, Taiwan, Thailand, United Kingdom, and United States. The Bayesian Information Criterion (BIC) was used to determine the best-fitting breakpoint model for the number of breakpoints and the break dates identified using the determined model.ResultsAggregated analysis of these HDV and HBV datasets spanning 1999-2020 identified structural breaks in the timeline of HDV incidence in 2002, 2012, and 2017. A significant increase in the international HDV incidence, relative to reported HBV diagnoses, occurred in 2013-2017. Secondary analysis identified four distinct temporal clusters of HDV incidence, including Cluster I (Macao, Taiwan), Cluster II (Argentina, Brazil, Germany, Thailand), Cluster III (Bulgaria, Netherlands, New Zealand, United Kingdom, United States), and Cluster IV (Australia, Austria, Canada, Finland, Norway, Sweden).ConclusionRe-evaluation of the testing paradigm for HDV in HBV-positive patients and an active surveillance status of HDV are warranted to define the etiology of the structural breaks in HDV incidence timelines.

BACKGROUND: Hepatitis delta is the most aggressive form of chronic viral hepatitis. We examined the clinical burden, epidemiological features and time trends for hepatitis delta patients hospitalized in Spain during the last two decades. METHODS: Retrospective, observational study using the Spanish National Registry of Hospital Discharges. Information was retrieved since 1997 to 2018. RESULTS: From a total of 79 647 783 nationwide hospital admissions recorded during the study period, 5179 included hepatitis delta as diagnosis. The overall hospitalization rate because of hepatitis delta was 6.5/105, without significant yearly changes. In-hospital death occurred in 335 (6.6%) patients. Acute hepatitis and cirrhosis were recorded in 46.5 and 33.5% of hepatitis delta hospitalizations, respectively. Acute hepatitis delta predominated until 2007 (55.9%) whereas cirrhosis increased since then (39.4%). Hepatic decompensation events and liver cancer accounted on average for 16 and 8% of hospitalizations, increasing significantly over time. Coinfection with HIV and hepatitis C virus (HCV) were recognized in 24 and 31.2% of hepatitis delta patients, respectively. All hepatitis C, HIV and injection drug use declined significantly since 2008. CONCLUSION: The rate of hepatitis delta in patients hospitalized in Spain is low and has remained stable over two decades. However, hepatitis delta-related decompensation events and liver cancer are on the rise. The association of hepatitis delta with injection drug use, HIV and HCV has declined among recently hospitalized hepatitis delta patients. Copyright

BackgroundHepatitis D Virus (HDV) is classified into eight genotypes with distinct clinical outcomes. Despite the maintenance of highly conserved functional motifs, it is unknown whether sequence divergence between genotypes, such as HDV-1 and HDV-3, or viral interference mechanisms may affect co-infection in the same host and cell, thus hindering the development of HDV inter-genotypic recombinants. We aimed to investigate virological differences of HDV-1 and HDV-3 and assessed their capacity to infect and replicate within the same liver and human hepatocyte in vivo.MethodsHuman liver chimeric mice were infected with hepatitis B virus (HBV) and with one of the two HDV genotypes or with HDV-1 and HDV-3 simultaneously. In a second set of experiments, HBV-infected mice were first infected with HDV-1 and after 9 weeks with HDV-3, or vice versa. Also two distinct HDV-1 strains were used to infect mice simultaneously and sequentially. Virological parameters were determined by strain-specific qRT-PCR, RNA in situ hybridization and immunofluorescence staining.ResultsHBV/HDV co-infection studies indicated faster spreading kinetics and higher intrahepatic levels of HDV-3 compared to HDV-1. In mice that simultaneously received both HDV strains, HDV-3 became the dominant genotype. Interestingly, antigenomic HDV-1 and HDV-3 RNA were detected within the same liver but hardly within the same cell. Surprisingly, sequential super-infection experiments revealed a clear dominance of the HDV strain that was inoculated first, indicating that HDV-infected cells may acquire resistance to super-infection.ConclusionInfection with two largely divergent HDV genotypes could be established in the same liver, but rarely within the same hepatocyte. Sequential super-infection with distinct HDV genotypes and even with two HDV-1 isolates was strongly impaired, suggesting that virus interference mechanisms hamper productive replication in the same cell and hence recombination events even in a system lacking adaptive immune responses.

Hepatitis delta virus (HDV) is a highly pathogenic virus and causes rapid disease progression from fulminant hepatitis to development of hepatocellular carcinoma in patients infected with hepatitis B virus (HBV). HDV is endemic in Pakistan; however, there are no available data on HDV prevalence among the high-risk group of HBV-infected pregnant women. A total of 1,394 pregnant women, visiting different public-sector hospitals in Lahore, were enrolled in this study. Their demographic data and blood samples were collected from May 2016 to July 2017. Samples were screened for both HBsAg and anti-HDV. Anti-HDV positive samples were tested for HDV RNA, and samples positive for HDV RNA were further sequenced to determine the HDV genotype. Of the 1,394 samples, HBsAg was positive in 63 (4.5%). Of these 63 HBsAg-positive samples, 13 (20.63%) were positive for anti-HDV. Of the 13 HBsAg/anti-HDV positive samples, HDV RNA was detected in 4 (30.8%) samples and all 4 carried HDV genotype 1. The age of enrolled women varied from 20 to 40 years, with most of the women living in urban areas, having education more than secondary school level, belonging to middle class, and being housewives. Majority of the tested women were of age from 25 to 30 years (39.2%); however, the prevalence of HBV was higher in age group 31-35 years (10.7%, confidence interval [CI]: 4.73-16.67); however, anti-HDV prevalence was 1.9% (CI: -0.7 to 4.7). This study is the first report on HDV prevalence among pregnant women in Pakistan. Our study showed a high predominance of HDV (20.63%) in HBV-infected pregnant women and the prevalence of HDV genotype 1 infection. The findings contribute to a better understanding of the HDV/HBV coinfection among pregnant women and circulating HDV genotypes in the country.

Aim: The aim of this study was to investigatethe detection, rates and correlations of Torque Teno Virus (TTV) and Hepatitis Delta Virus (HDV) whichcause superinfection and coinfection in patients with chronic hepatitis B inTokat.Materialand Methods: A total of 110patients with chronic HBV infection (58 women, 52 men) and 90 healthy subjectswere included in the study. Polymerase chain reactions (PCR) of all blood sampleswere performed with TTV-DNA and HDV-RNA isolations. Aspartate aminotransferase (AST)and alanine aminotransferase (ALT) values of patients were also studied.Results:108 samples of the patients were HDV-RNA negative and 2 were (1.81%) HDV-RNApositive. HDV-RNA were negativein all healthy subjects. Inthe TTV study, 106 of the 110 samples (96.4%) were found to be TTV-DNA positivewhile 4 were found to be TTV-DNA negative. Inhealthy subjects, 86 of 90 samples (95.35%) were TTV-DNA positive and 4 (4.65%)were TTV-DNA negative. Astatistically significant relationship was found between ALT and AST values inHDV-RNA positive patients (p0.05).Conclusion:It has seen that the rate of HDV infection in Tokat province is considerablylower than the average of Turkey and in the World. Torque Teno Virus, which wasinvestigated for the first time in Tokat, is higher than the average of Turkeyand World. There was no statistically significant relationship between theinfections of Torque Tenovirus and hepatitis deltavirus in patients withchronic hepatitis B infections., Amaç: Tokatilinde kronik hepatit B tanılı hastalarda Hepatit Delta Virüs (HDV) ve TorkTeno Virüs (TTV) araştırması yapıldı.Gereç ve Yöntemler:Çalışma Ocak 2015-Temmuz 2015 tarihleri arasında Gaziosmanpaşa Üniversitesi TıpFakültesi Mikrobiyoloji Anabilim Dalında gerçekleştirildi. Çalışmaya Kronik HBV’li110 hasta (58’i kadın, 52’si erkek) ve 90 sağlıklı birey dahil edildi. Hastakanlarından izole edilen TTV-DNA veHDV-RNA’ların polimeraz zincir reaksiyonları (PZR) yapıldı. Ayrıca hastalardaaspartat aminotransferaz (AST), alanin aminotransferaz (ALT) değerleri deçalışıldı.Bulgular:Hasta numunelerinin 108’i HDV-RNA negatif, 2’si (%1,81) HDV-RNA pozitif olaraktespit edildi. Sağlıklı bireylerin tümünde HDV-RNA negatif bulundu. TTV çalışmasındaise 110 numunenin 106’sı (%96,4) TTV-DNA pozitif olarak bulunurken, 4’ü TTV-DNAnegatif olarak tespit edildi. Sağlıklı bireylerde ise 90 numunenin 86’sının(%95,35) TTV-DNA pozitif, 4’ünün (%4,65) TTV-DNA negatif olduğu tespit edildi. HDV-RNApozitif olan hastalarda ALT ve AST değerleri arasında istatiksel olarak anlamlıbir ilişki tespit edilirken (p0,05).Sonuç:Tokat ilinin, HDV enfeksiyon oranı, Türkiye ortalamasının oldukça altında, dünyagenelinde ise, çok düşük endemisite grubuna dahil bölgeler arasında olduğugörüldü. Tokat’ta ilk defa araştırılan TorkTenovirüs ise %96 oranı ile dünya veTürkiye ortalamasının oldukça üzerindedir. Kronik hepatit B enfeksiyonlu hastagrubunda araştırılan TorkTenovirüs ve hepatit deltavirüs enfeksiyonlarıarasında istatistiksel açıdan anlamlı bir ilişki saptanmamıştır.

Hepatitis delta (HDV) virus still poses a serious health problem worldwide. Being a satellite particle, it may complete its life cycle only in the presence of HBs antigen produced by hepatitis B virus (HBV). According to epidemiological data, about 5% of HBs antigen carriers are infected with this virus, which equates to approximately 15-20 million individuals worldwide. Although the infection with both HBV and HDV viruses is considered to be the worst form of viral hepatitis, the only approved treatment, with pegylated interferon α, is not satisfactory. Thus effective and safe therapy is still lacking, which stands in contrast to the latest development in therapeutic areas of HBV and hepatitis C virus (HCV) infections. As the exact data on prevalence of this infection in some countries as well as natural history of this disease are still incomplete, further studies are warranted. Polish investigations on this field are very scarce and at most dating from the 1990s. This publication makes another attempt to broaden our knowledge of this temporarily forgotten but still ongoing and complex problem.

Chronic delta hepatitis is the most severe form of viral hepatitis affecting nearly 65 million people worldwide. Individuals with this devastating illness are at higher risk for developing cirrhosis and hepatocellular carcinoma. Delta virus is a defective RNA virus that requires hepatitis B surface antigen for propagation in humans. Infection can occur in the form of a co-infection with hepatitis B, which can be self-limiting, vs superinfection in a patient with established hepatitis B infection, which often leads to chronicity in majority of cases. Current noninvasive tools to assess for advanced liver disease have limited utility in delta hepatitis. Guidelines recommend treatment with pegylated interferon, but this is limited to patients with compensated disease and is efficacious in about 30% of those treated. Due to limited treatment options, novel agents are being investigated and include entry, assembly and export inhibitors of viral particles in addition to stimulators of the host immune response. Future clinical trials should take into consideration the interaction of hepatitis B and hepatitis D as suppression of one virus can lead to the activation of the other. Also, surrogate markers of treatment efficacy have been proposed.

Background & aims The sodium taurocholate co-transporting polypeptide (NTCP) is the entry receptor for the hepatitis B and delta virus (HBV/HDV) and the main hepatic uptake transporter of conjugated bile acids. Myrcludex B, a synthetic peptide mimicking the NTCP-binding domain of HBV, blocks HBV/HDV infection and inhibits NTCP-mediated bile acid uptake. In humans this increases systemic bile acid levels, which remain elevated for hours even after Myrcludex B is cleared from the circulation. Here, we investigated the dynamics of Myrcludex B-induced NTCP-mediated bile acid transport inhibition in mice and if/how the duration of this effect relates to NTCP protein turnover. Methods Plasma bile acids were determined in Myrcludex B-treated OATP1a/1b-deficient mice. In vitro, plasma membrane-resident NTCP was labeled with biotin or fluorescein isothiocyanate (FITC)-labeled Myrcludex B and traced in time using hNTCP-overexpressing U2OS cells. Förster resonance energy transfer by fluorescent lifetime imaging microscopy was used to investigate whether Myrcludex B can transfer to newly synthesized NTCP. Results Conjugated bile salt levels in plasma peaked 4 h after subcutaneous Myrcludex B administration. After 24 h, plasma bile salt levels were completely normalized, in line with restored NTCP-mediated bile acid transport in vitro. Biotin-labeled NTCP disappeared faster than Myrcludex B-FITC, with almost 40% of FITC signal remaining after 24 h. FITC fluorescence lifetime was strongly decreased upon expression of DY547-labeled acyl carrier protein-tagged NTCP, demonstrating transfer of pre-bound Myrcludex B-FITC to newly formed NTCP. Conclusions The dynamics of NTCP protein turnover and Myrcludex B-induced plasma bile salt elevations are similar, suggesting that the Myrcludex B:NTCP interaction is very long-lived. Nevertheless, Myrcludex B is not completely degraded together with NTCP and can transfer to newly synthesized NTCP. Lay summary The experimental drug Myrcludex B binds the sodium taurocholate co-transporting polypeptide (NTCP), the viral entry receptor for the hepatitis B and D virus (HBV/HDV), and thereby prevents infection, but also inhibits hepatic bile salt uptake leading to transiently elevated bile salt levels. This study describes that while the normalization of plasma bile salt levels likely depends on the protein turnover rate of NTCP, Myrcludex B partly escapes co-degradation with NTCP by transferring from one NTCP molecule to another. This is of importance to the HBV/HDV research field as it provides a potential explanation for the distinct kinetics and dose-dependence of Myrcludex B’s effects on viral infection versus bile salt transport., Graphical Abstract Unlabelled Image, Highlights • Myrcludex B-induced plasma bile salt elevations coincide with NTCP protein turnover. • NTCP-bound Myrcludex B can transfer from one NTCP molecule to another. • Transfer to newly synthesized NTCP might extend the inhibitory potential of Myrcludex B. • 50% occupation of NTCP by Myrcludex B is not enough to block bile acid transport.

As Delta problem moved from the shadow up on the stage, becoming one of the most crucial disease in Hepatology area, our STC 2019 is dedicated to hepat itis D, for the first time in the history of APASL STC topics. As hepatitis Delta occurs only with HBV infection, we will discuss hepatitis B, its epidemiology, work - up, current treatment and new horizons in the developing pharmaceutical agents. The scient ific program will include the topics presented by the best speakers and the experts in Delta and B hepatitis. This conference is a good chance to meet and interact with leading clinical professionals and researches and to obtain latest information for hepa tologists.

Introduction: Hepatitis D virus, a defective virus that requires active hepatitis B virus replication, can only infect people with active HBV infection. The clinical picture of patients super-infected with HDV proceeds rapidly and progressively. Eventually, cirrhosis, liver failure and hepatocellular carcinoma may occur. In this study, it was aimed to investigate both HDV seroprevalence and coinfection/ superinfection frequency in HDV infected patients in our region. Materials and Methods: A total of 740 patients (2015-2018) with HBsAg positivity were included in the study. The results of HDV Ab, HDV Ag, anti-HBe, HBe Ag, anti-HBc IgM and IgG, ALT and AST were examined in these patients. Results: 60% of the patients were males and 40% were females. HDV Ab positivity was detected in 10 (1.36%) of the 740 HBsAg positive patients. HDV Ag positivity was detected in four patients, whereas HDV Ag and Ab positivity was detected in only one patient. ALT and AST elevations were found in 3 of the patients (30%) with Delta antibody positivity. Anti-HBc IgG was positive in all patients with Delta ab positivity and there was no antiHBcIgM positivity. Conclusion: In this study, HDV prevalence detected in our region was 1.36%, which is below the general average of Turkey. There is superinfection in the whole of what we identify as HDV Ab positive. In order to combat HDV infection, in addition to immunizing those who have not had Hepatitis B infection and the nonimmune community, transmission routes of HBV must be enlightened and the epidemiology of the disease must be well known. Screening of HBV-infected individuals for HDV will help identify infected persons and contribute to protection, control and treatment programs.

International audience; Virus-related liver carcinogenesis is one of the main contributors of cancer-related death worldwide mainly due to the impact of chronic hepatitis B and C infections. Three mechanisms have been proposed to explain the oncogenic properties of hepatitis B virus (HBV) infection: induction of chronic inflammation and cirrhosis, expression of HBV oncogenic proteins, and insertional mutagenesis into the genome of infected hepatocytes. Hepatitis B insertional mutagenesis modifies the function of cancer driver genes and could promote chromosomal instability. In contrast, hepatitis C virus promotes hepatocellular carcinoma (HCC) occurrence mainly through cirrhosis development whereas the direct oncogenic role of the virus in human remains debated. Finally, adeno associated virus type 2 (AAV2), a defective DNA virus, has been associated with occurrence of HCC harboring insertional mutagenesis of the virus. Since these tumors developed in a non-cirrhotic context and in the absence of a known etiological factor, AAV2 appears to be the direct cause of tumor development in these patients via a mechanism of insertional mutagenesis altering similar oncogenes and tumor suppressor genes targeted by HBV. A better understanding of virus-related oncogenesis will be helpful to develop new preventive strategies and therapies directed against specific alterations observed in virus-related HCC.

Chronic hepatitis D virus infection is the most severe form of viral hepatitis. Antiviral treatment is urgently needed to prevent patients from developing end stage liver disease or hepatocellular carcinoma. Treatment options were limited to off-label use of pegylated interferon alfa until conditional approval of bulevirtide by the EMA (European Medicines Agency) in July 2020. However, several other antiviral compounds are currently investigated and represent promising agents for the treatment of chronic HDV infection.

Background Hepatitis delta virus (HDV) infection is the most aggressive form of chronic viral hepatitis. Response rates to therapy with 1- to 2-year courses of pegylated interferon alpha (peginterferon) treatment are suboptimal. Aims To evaluate the long-term outcomes of patients with chronic hepatitis D after an extended course of peginterferon. Methods Patients were followed after completion of trial NCT00023322 and classified based on virological response defined as loss of detectable serum HDV RNA at last follow-up. During extended follow-up, survival and liver-related events were recorded. Results All 12 patients who received more than 6 months of peginterferon in the original study were included in this analysis. The cohort was mostly white (83%) and male (92%) and ranged in age from 18 to 58 years (mean = 42.6). Most patients had advanced but compensated liver disease at baseline, a median HBV DNA level of 536 IU per mL and median HDV RNA level of 6.86 log10 genome equivalents per mL. The treatment duration averaged 6.1 years (range 0.8-14.3) with a total follow-up of 8.8 years (range 1.7-17.6). At last follow-up, seven (58%) patients had durable undetectable HDV RNA in serum, and four (33%) cleared HBsAg. Overall, one of seven (14%) responders died or had a liver-related event vs four of five (80%) non-responders. Conclusions With further follow-up, an extended course of peginterferon therapy was found to result in sustained clearance of HDV RNA and favourable clinical outcomes in more than half of patients and loss of HBsAg in a third.

Within the hepatitis virus landscape, one incomplete virus, the hepatitis delta virus (HDV), appears to differ from hepatitis B and C viruses in the context as it still may not infrequently lead to complications of chronic liver disease and continues to be associated with significant liver-related mortality even when patients have received available treatment for it. Breakthrough therapies are so far lacking for HDV-infected patients and treatment has not changed since the discovery of HDV in 1977 and consists mainly of interferons. While there was little interest on the global epidemiology of HDV until recently, this has changed in the past 2 years and we are currently observing a stream of papers on the global epidemiology of HDV and commentaries about why prevalence estimates appear to differ so dramatically. This may be related to the fact that reliable data are not available for most of the countries. However, in the industrialized world, data on the epidemiology of HDV are expected to be of better overall quality. Hence, this review was undertaken to provide a detailed overview on the epidemiology of HDV infection in industrialized countries using data from representative larger countries. In industrialized countries, with maybe the exception of China, HDV infection is a disease of high-risk groups. Migrant groups and people who inject drugs are the most encountered high-risk groups. This review summarizes the dynamics of their contribution to the HDV epidemiology in industrialized countries of the west and the east.

Background: Hepatitis delta is the most aggressive form of chronic viral hepatitis. We examined the clinical burden, epidemiological features and time trends for hepatitis delta patients hospitalized in Spain during the last two decades. Methods: Retrospective, observational study using the Spanish National Registry of Hospital Discharges. Information was retrieved since 1997 to 2018. Results: From a total of 79 647 783 nationwide hospital admissions recorded during the study period, 5179 included hepatitis delta as diagnosis. The overall hospitalization rate because of hepatitis delta was 6.5/10(5), without significant yearly changes. In-hospital death occurred in 335 (6.6%) patients. Acute hepatitis and cirrhosis were recorded in 46.5 and 33.5% of hepatitis delta hospitalizations, respectively. Acute hepatitis delta predominated until 2007 (55.9%) whereas cirrhosis increased since then (39.4%). Hepatic decompensation events and liver cancer accounted on average for 16 and 8% of hospitalizations, increasing significantly over time. Coinfection with HIV and hepatitis C virus (HCV) were recognized in 24 and 31.2% of hepatitis delta patients, respectively. All hepatitis C, HIV and injection drug use declined significantly since 2008. Conclusion: The rate of hepatitis delta in patients hospitalized in Spain is low and has remained stable over two decades. However, hepatitis delta-related decompensation events and liver cancer are on the rise. The association of hepatitis delta with injection drug use, HIV and HCV has declined among recently hospitalized hepatitis delta patients.

Envisioning a hepatitis delta cure with new antivirals

Background Current literature on the prevalence and characteristics of hepatitis D virus (HDV) infection in young adults is limited. This study aims to determine the disease characteristics and severity in young adults. Methods The case records of HDV RNA positive patients of age 18-25 years were analyzed. Results Out of 119 patients, 105 (88%) patients were male. HBV-DNA was detectable in 83 (70%). Hepatitis B e-antigen (HBeAg) was non-reactive in 99 (83%). Cirrhosis was identified in 45 (37.8%) individuals; nine (7.5%) were classified as Child class B or Child class C. Twenty-four (20.2%) had a Model For End-Stage Liver Disease (MELD) score of ≥10, out of these 16 had a score of 15 or more. The risk of decompensation was calculated according to the Baseline-event-anticipation (BEA) score; eight (6.7%) patients were at BEA-A (mild risk), 105 (88.2%) were at BEA-B (moderate risk), and six (5.0%) were at BEA-C (severe risk). Notable findings in patients with cirrhosis included splenomegaly, low total leucocyte counts, low platelets, high bilirubin, elevated aspartate aminotransferase, gamma-glutamyl transferase and international normalization ratio, low albumin, high AST to Platelet Ratio Index (APRI), and high BEA score. The splenic size, platelet count, and albumin levels were independently associated with cirrhosis (p < 0.001

The role of low levels of HDV-RNA during and after interferon therapy of hepatitis D is unknown. We re-analysed HDV RNA in 372 samples collected in the HIDIT-2 trial (Wedemeyer et al, Lancet Infectious Diseases 2019) with the Robogene assay (RA; Jena Analytics). Data were compared with the previously reported in-house assay (IA). We detected HDV-RNA in one-third of samples previously classified as undetectable using the highly sensitive RA. Low HDV viraemia detectable at week 48 or week 96 was associated with a high risk for post-treatment relapse, defined as HDV RNA positivity in both assays at week 120. HDV RNA relapses occurred in 10/15 (67%) patients with detectable low HDV RNA at week 48 and in 10/13 (77%) patients with low viraemia samples at week 96. in contrast, the post-treatment relapse rate was lower in patients with undetectable HDV RNA in both assays during treatment., Projekt DEAL, Open access funding enabled and organized by Projekt DEAL.

Revisiting replicating RNAs DNA-dependent RNA polymerases are well known for their ability to produce RNA from DNA templates. Much less is known about their noncanonical activity: the generation and replication of RNA from RNA templates. Deeper insights into this process could shed light on questions relating to the origin of life, molecular evolution, and the replication of certain RNA pathogens such as hepatitis delta virus and plant viroids. Jain et al. explore in detail how the bacteriophage T7 RNA polymerase generates and amplifies diverse RNA sequences in vitro. Using sequencing, microfluidics, and bioinformatics, they chart the emergence and evolution of replicating RNA motifs and identify mechanisms that explain their selection and structures. Science , this issue p. eaay0688

International audience; Le virus de l'hépatite Delta Un agent pathogène qui retourne facilement sa veste ? Anaïs Vignon, Solène Denolly, Jimena Perez-Vargas, François-Loïc Cosset > Le virus de l'hépatite Delta (VHD) a été découvert il y a 40 ans dans le foie de personnes infectées par le virus de l'hépatite B (VHB, de la famille des Hepadnaviridae). Parmi les 250 millions de personnes chroniquement infectées par VHB, 15 à 20 millions sont coinfectées par VHD [1]. La surinfection par VHD aggrave l'hépatite déjà causée par VHB, et augmente le risque de développer cirrhose et hépatocarcinome [2]. Du fait de son association avec VHB, VHD est connu en tant que virus « satellite » de VHB, ce qui signifie qu'il en est dépendant (Figure 1) [3]. La particule virale de VHD est formée d'un complexe ribonucléoprotéique constitué du génome viral à ARN associé aux deux formes structurelles de la protéine codée par VHD, S-HDAg et L-HDAg, et repose sur les glycoprotéines de surface de VHB pour l'assemblage des virions, leur enveloppement et leur transmission cellulaire (Figure 1A). Ainsi, pour que VHD puisse former sa particule virale et se disséminer, VHB doit être présent dans la même cellule. Lorsque VHB est absent, VHD reste capable de se répliquer et reste plusieurs semaines dans la cellule, mais il est incapable de se disséminer (Figure 1B) [2]. Cependant, l'idée que VHB est l'unique virus « assistant » utilisé par VHD a récemment été remise en cause. En effet, le génome et les protéines de VHD ont été détectés dans les glandes salivaires de patients atteints du syndrome de Sjögren (une maladie auto-immune systémique), alors que ni les séquences génomiques de VHB ni des anticorps

Despite the availability of both effective preventive vaccines and oral antivirals, over 250 million people are chronically infected with the hepatitis B virus (HBV). Globally, chronic hepatitis B is the leading cause of hepatocellular carcinoma, which represents the third cause of cancer mortality, accounting for nearly 1 million annual deaths. Current oral nucleos(t)ide therapy with tenofovir or entecavir suppresses serum HBV-DNA in most treated patients, but rarely is accompanied by HBsAg loss. Thus, treatment has to be given lifelong to prevent viral rebound. A broad spectrum of antivirals that block the HBV life cycle at different steps are in clinical development, including entry inhibitors, cccDNA disrupters/silencers, translation inhibitors, capsid assembly modulators, polymerase inhibitors and secretion inhibitors. Some of them exhibit higher potency than current oral nucleos(t)ides. Drugs in more advanced stages of clinical development are bulevirtide, JNJ-6379, ABI-H0731, ARO-HBV and REP-2139. To date, only treatment with ARO-HBV and with REP-2139 have resulted in HBsAg loss in a significant proportion of patients. Combination therapies using distinct antivirals and/or immune modulators are expected to maximize treatment benefits. The current goal is to achieve a 'functional cure', with sustained serum HBsAg after drug discontinuation. Ultimately, the goal of HBV therapy will be virus eradication, an achievement that would require the elimination of the cccDNA reservoir within infected hepatocytes.

International audience

WOS: 000441968900004, Objectives: The present study aims to investigate biochemical, virological and histological characteristics of hepatitis delta virus infection, which is a serious problem in our region, as well as its relationship with chronic hepatitis B virus (HBV) infection and cirrhosis. Materials and Methods: A total of 220 patients were included in the study. The patients were divided into three groups: group 1 included patients with hepatitis delta virus-related cirrhosis (DA cirrhosis), group 2 consisted of patients with chronic delta hepatitis (CHD) and group 3 composed of patients with chronic hepatitis B (CHB). Biochemical and virological parameters of the patients were analyzed. Patients with CHB and CHD underwent biopsy for histological examination. The results were compared among the three groups. Results: Seventy-five (34.09%) of the patients were women, 145 (65.90%) were males and their mean age was 38.04 years. There were 44 patients (20%) with delta hepatitis-associated cirrhosis, 86 patients with CHD (39.09%) and 90 patients with CHD (40.9%). HBV DNA level was significantly lower in patients with cirrhosis and chronic delta hepatitis than in patients with CHB (p