Delta Virus Infection Research Articles

MiRNome profiling of circulating extracellular vesicles in patients with chronic hepatitis delta treated with pegylated interferon alpha

Introduction: MicroRNAs (miRNAs) are short noncoding RNAs involved in the epigenetic regulation of multiple signalling pathways including modulation of viral replication and host immune antiviral response. Specific circulating miRNAs profiles have been associated both with the progression of chronic hepatitis C and with the response to interferon (IFN) treatment in chronic hepatitis B patients. However, data in patients with chronic hepatitis delta virus (HDV) infection are missing.

New actors come into play against hepatitis delta.

Currently chronic hepatitis delta (CHD) represents the most severe form of chronic viral hepatitis. The risk of developing cirrhosis, hepatocellular carcinoma (HCC) and decompensated liver disease is 2-3 times greater in hepatitis delta virus (HDV) infection than in hepatitis B virus (HBV). For instance, in a study carried out in Italy including 299 CHD patients followed for 28 years, 82 (27%) developed cirrhosis, and among these, 46 (56%) developed HCC. The real number of subjects infected by HDV worldwide remains unknown due to the lack of information in many areas, though it has been suggested that the rate of HBsAg carriers co-infected by HDV may be situated between 4.5 and 18%.

Prevalence of Hepatitis D virus antibodies in Hepatitis B patients treated at tertiary care unit at Jabalpur Central India

Hepatitis Delta virus (HDV) infection amongst Hepatitis B virus (HBV) infected patients increases morbidity and mortality. The prevalence varies temporally and spatially. The present study aimed to evaluate the HDV prevalence in central India. Samples received from January 2018 to December 2019 were tested for viral hepatitis markers. Randomly picked 372 HBsAg positive samples were tested for the presence of HDV total antibodies using ELISA, of these 8 were found positive. This study for the first-time documents presence of HDV with 2.1% prevalence from central India. We recommend screening for better patient management and bringing down the disease burden.

Comprehensive Analysis of Hepatitis Delta Virus Assembly Determinants According to Genotypes: Lessons From a Study of 526 Hepatitis Delta Virus Clinical Strains.

Human hepatitis Delta virus (HDV) infection is associated to the most severe viral hepatic disease, including severe acute liver decompensation and progression to cirrhosis, and hepatocellular carcinoma. HDV is a satellite of hepatitis B virus (HBV) that requires the HBV envelope proteins for assembly of HDV virions. HDV and HBV exhibit a large genetic diversity that extends, respectively to eight (HDV-1 to -8) and to ten (HBV/A to/J) genotypes. Molecular determinants of HDV virion assembly consist of a C-terminal Proline-rich domain in the large Hepatitis Delta Antigen (HDAg) protein, also known as the Delta packaging domain (DPD) and of a Tryptophan-rich domain, the HDV matrix domain (HMD) in the C-terminal region of the HBV envelope proteins. In this study, we performed a systematic genotyping of HBV and HDV in a cohort 1,590 HDV-RNA-positive serum samples collected between 2001 to 2014, from patients originated from diverse parts of the world, thus reflecting a large genetic diversity. Among these samples, 526 HBV (HBV/A, B, C, D, E, and G) and HDV (HDV-1, 2, 3, and 5 to -8) genotype couples could be obtained. We provide results of a comprehensive analysis of the amino-acid sequence conservation within the HMD and structural and functional features of the DPD that may account for the yet optimal interactions between HDV and its helper HBV.

HBcrAg Levels Are Associated With Virological Response to Treatment With Interferon in Patients With Hepatitis Delta.

Standard treatment of hepatitis delta virus (HDV) infection remains pegylated‐interferon alfa (peg‐IFNα) in most centers, which is not only associated with rather low efficacy but several adverse events. Hepatitis B core‐related antigen (HBcrAg) is linked to intrahepatic covalently closed circular DNA levels and has previously been suggested as response predictor in IFN‐based treatment of hepatitis B virus (HBV) mono‐infection. This study aimed to investigate the value of HBcrAg in the management of patients with HBV/HDV co‐infection undergoing peg‐IFNα treatment. The Hep‐Net‐International‐Delta‐Hepatitis‐Intervention Trial‐2 study included 120 patients co‐infected with HBV/HDV. Patients were treated for 96 weeks with peg‐IFNα and either tenofovir or placebo. Ninety‐nine patients with HDV‐RNA results 24 weeks after end of treatment (FU24) were included in this analysis, of whom 32 patients (32.3%) had undetectable HDV RNA at FU24. HBcrAg was measured at baseline, week 12, 24, 48, 96, and FU24. HBcrAg levels showed no significant correlation with HDV RNA but were significantly linked to treatment outcome. HBcrAg levels < 4.5 log IU/mL at baseline, week 24, and week 48 had high negative predictive value (NPV) for achieving undetectable HDV RNA at FU24 (81.8%, 87.1% and 95.0%, respectively). Similarly, HBcrAg levels at week 96 were significantly higher in patients with viral relapse until FU24 (3.0 vs. 3.63 log IU/mL; P = 0.0089). Baseline, week 24, and week 48 HBcrAg levels were also associated with the likelihood of achieving HBsAg level < 100 IU/mL at FU24 (HBcrAg < 3.0 log IU/mL: NPV 91.7%, 90.4% and 92.3%, respectively). Test statistics improved when combining HBcrAg with additional viral and clinical parameters. Conclusion: HBcrAg is linked to treatment response to peg‐IFNα in patients with HBV/HDV co‐infection and could be a promising marker to determine treatment futility.

Inhibitory effect of a novel thiazolidinedione derivative on hepatitis B virus entry

The development of novel antivirals to treat hepatitis B virus (HBV) infection is still needed because currently available drugs do not completely eradicate chronic HBV in some patients. Recently, troglitazone and ciglitazone, classified among the compounds including the thiazolidinedione (TZD) moiety, were found to inhibit HBV infection, but these compounds are not clinically available. In this study, we synthesized 11 TZD derivatives, compounds 1–11, and examined the effect of each compound on HBV infection in HepG2 cells expressing NTCP (HepG2/NTCP cells). Among the derivatives, (Z)-5-((4'-(naphthalen-1-yl)-[1,1′-biphenyl]-4-yl)methylene)thiazolidine-2,4-dione (compound 6) showed the highest antiviral activity, with an IC50 value of 0.3 μM and a selectivity index (SI) of 85, but compound 6 did not affect HCV infection. Treatment with compound 6 inhibited HBV infection in primary human hepatocytes (PHHs) but did not inhibit viral replication in HepG2.2.15 cells or HBV DNA-transfected Huh7 cells. Moreover, treatment with compound 6 significantly impaired hepatitis delta virus (HDV) infection and inhibited a step in HBV particle internalization but did not inhibit attachment of the preS1 lipopeptide or viral particles to the cell surface. These findings suggest that compound 6 interferes with HBV infection via inhibition of the internalization process.

Bulevirtide in chronic hepatitis D: a profile of its use

Bulevirtide (HEPCLUDEX®), a first-in-class entry inhibitor, is a new option for the treatment of chronic hepatitis D, caused by hepatitis delta virus (HDV) infection, in HDV-RNA positive adults with compensated liver disease. In a pivotal phase IIb trial in patients with chronic hepatitis D, treatment with bulevirtide in combination with tenofovir significantly reduced HDV RNA levels compared with treatment of the underlying HBV infection with tenofovir alone. Alanine aminotransferase (ALT) levels were also normalised by bulevirtide combination therapy. Bulevirtide is generally well tolerated; the most common adverse event in clinical trials was dose-dependent and asymptomatic increase in bile salts (reversible upon treatment discontinuation).

Early virological response in six patients with hepatitis D virus infection and compensated cirrhosis treated with Bulevirtide in real-life.

Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Bulevirtide (BLV, Hepcludex® ) is an HDV/HBV entry inhibitor approved in June 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease and positive HDV RNA viral load. This real-life preliminary report described early virological efficacy and safety of BLV in six patients with CHD and compensated liver disease: four patients were treated with the combination of BLV (2mg/d in subcutaneous injection) and pegylated interferon (PEG-IFN) and two patients with BLV monotherapy. Four patients treated with combined therapy had a decline of a minimum of 1log10 and 3/3 of 2log10 of HDV-VL at 12 and 24 weeks, respectively. One patient among four had stopped the treatment at 12 weeks because of thrombocytopenia and an HDV-VL relapse was notified 24weeks after treatment cessation. Three patients among four (3/4) had undetectable HDV-VL during the therapy (<100IU/ml). One patient (1/2) treated with BLV monotherapy had a decline of HDV-VL by 1log10 at 8 weeks and 1/1 by 2log10 at 28 week on-treatment. Two patients among four (2/4) with combined therapy had normal ALT reached at 4 and 56 weeks. One patient (1/2) with BLV monotherapy achieves ALT normalization at​ 4 weeks on treatment. Hepatitis B surface antigen (HBsAg) levels remain unchanged. Three among six (3/6) patients had an elevation of total biliary acids without pruritus. These early data generated confirm the interest in this new treatment. Final results will be important to demonstrate long-term clinical benefit (fibrosis reversibility and reduction in hepato-cellular carcinoma [HCC]).

New therapies for hepatitis delta virus infection.

Hepatitis delta virus (HDV) infection is a defective virus requiring hepatitis B virus (HBV) for its complete replication cycle. HDV is a small hepatotropic RNA virus and around 15 to 25 million people worldwide are living with chronic hepatitis delta (CHD) infection. However, the prevalence of HDV may be underestimated, and screening is frequently insufficient. HDV infection remains endemic in several regions including Central and West Africa, the Mediterranean basin, the Middle East, Eastern Europe, Northern Asia, certain areas of Southeast Asia and the Amazon basin of South America. The best preventive strategy to decrease HDV infection is to improve coverage of the prophylactic HBV vaccine. HDV infection may occur by HBV-HDV co-infection or superinfection, and the latter is usually more severe. CHD is associated with a higher risk of cirrhosis and hepatocellular carcinoma (HCC) compared to HBV mono-infection. Pegylated interferon alpha (PEG-IFNα) therapy is limited by moderate effectiveness (around 20%) and its adverse effects. The entry inhibitor, bulevirtide (BLV, Hepcludex® ), which was recently approved in Europe at a dose of 2mg in sub-cutaneous injection per day, is indicated for the treatment of CHD in adult patients with compensated liver disease and positive HDV viremia. BLV can be administrated in monotherapy or in combination with PEG-IFNα. Nucleos(t)ide analogues can be used in combination for underlying HBV infection. The optimal treatment duration has not yet been determined and treatment should be continued if a clinical benefit is observed. There are other promising therapies such as IFN lambda (IFNλ) (immunomodulator), lonafarnib (prenylation inhibitor) and nucleic acid polymers (Inhibitors of HBsAg release). In this review, we will present an update on CHD and future promising treatments.

AAV-HDV: An Attractive Platform for the In Vivo Study of HDV Biology and the Mechanism of Disease Pathogenesis.

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis, but little is known about the molecular mechanisms involved. We have recently developed an HDV mouse model based on the delivery of HDV replication-competent genomes using adeno-associated vectors (AAV), which developed a liver pathology very similar to the human disease and allowed us to perform mechanistic studies. We have generated different AAV-HDV mutants to eliminate the expression of HDV antigens (HDAgs), and we have characterized them both in vitro and in vivo. We confirmed that S-HDAg is essential for HDV replication and cannot be replaced by L-HDAg or host cellular proteins, and that L-HDAg is essential to produce the HDV infectious particle and inhibits its replication. We have also found that lack of L-HDAg resulted in the increase of S-HDAg expression levels and the exacerbation of liver damage, which was associated with an increment in liver inflammation but did not require T cells. Interestingly, early expression of L-HDAg significantly ameliorated the liver damage induced by the mutant expressing only S-HDAg. In summary, the use of AAV-HDV represents a very attractive platform to interrogate in vivo the role of viral components in the HDV life cycle and to better understand the mechanism of HDV-induced liver pathology.

HBV/HDV Co-Infection: Epidemiological and Clinical Changes, Recent Knowledge and Future Challenges.

Several investigations have been published on Hepatitis Delta Virus (HDV) infection in recent years, from which we have drawn the salient data to provide readers with useful information to improve their knowledge on the subject. HDV genotypes 5–8 have been recently imported to Western countries from central Africa, whose clinical relevance deserves further investigation. Ongoing HDV replication has been identified as an independent predictor of progression to cirrhosis and HCC for patients with HDV chronic hepatitis (HDV-CH). Long-term treatments of HDV-CH with standard or pegylated interferon alfa (peg-IFN-α) have all been unsatisfactory, leading to a sustained virological response (SVR) only in 20–30% of patients treated, faced with a poor tolerability and frequent serious adverse reactions; the addition of HBV nucleo(s)tide analogues to peg-IFN- α did not improve the rate of SVR. The improved knowledge of the HDV life cycle has allowed the development of direct acting agents towards key-points of the HDV life cycle, namely bulevirtide, lonafarnib and nucleic acid polymers. Preliminary data have shown that these drugs are more effective than interferon-based therapies, but adverse reactions are also common, which however seem toned down in combination therapy with other antivirals.

Microarray Data Mining and Preliminary Bioinformatics Analysis of Hepatitis D Virus-Associated Hepatocellular Carcinoma.

Several studies have demonstrated that chronic hepatitis delta virus (HDV) infection is associated with a worsening of hepatitis B virus (HBV) infection and increased risk of hepatocellular carcinoma (HCC). However, there is limited data on the role of HDV in the oncogenesis of HCC. This study is aimed at assessing the potential mechanisms of HDV-associated hepatocarcinogenesis, especially to screen and identify key genes and pathways possibly involved in the pathogenesis of HCC. We selected three microarray datasets: GSE55092 contains 39 cancer specimens and 81 paracancer specimens from 11 HBV-associated HCC patients, GSE98383 contains 11 cancer specimens and 24 paracancer specimens from 5 HDV-associated HCC patients, and 371 HCC patients with the RNA-sequencing data combined with their clinical data from the Cancer Genome Atlas (TCGA). Afterwards, 948 differentially expressed genes (DEGs) closely related to HDV-associated HCC were obtained using the R package and filtering with a Venn diagram. We then performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the biological processes (BP), cellular component (CC), molecular function (MF), and KEGG signaling pathways most enriched for DEGs. Additionally, we performed Weighted Gene Coexpression Network Analysis (WGCNA) and protein-to-protein interaction (PPI) network construction with 948 DEGs, from which one module was identified by WGCNA and three modules were identified by the PPI network. Subsequently, we validated the expression of 52 hub genes from the PPI network with an independent set of HCC dataset stored in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, seven potential key genes were identified by intersecting with key modules from WGCNA, including 3 reported genes, namely, CDCA5, CENPH, and MCM7, and 4 novel genes, namely, CDC6, CDC45, CDCA8, and MCM4, which are associated with nucleoplasm, cell cycle, DNA replication, and mitotic cell cycle. The CDCA8 and stage of HCC were the independent factors associated with overall survival of HDV-associated HCC. All the related findings of these genes can help gain a better understanding of the role of HDV in the underlying mechanism of HCC carcinogenesis.

Hepatitis Delta Virus Infection among HIV/HBV and HBV-mono Infected Patients in Jos, Nigeria

Hepatitis Delta Virus Infection among HIV/HBV and HBV-mono Infected Patients in Jos, Nigeria

HBV-HDV co-infection: Alarming prevalence at a tertiary care Hospital, Karachi, Pakistan

Background: Pakistan is currently facing an epidemic of viral hepatitis due to B, C and D viruses which share parallel routes of transmission. Hepatitis D virus (HDV) can only replicate in individuals who are already infected with hepatitis B virus. Patients having HBV-HDV co-infection may have more severe disease and higher risk of fulminant hepatitis in acute cases and cirrhosis and hepatocellular carcinoma in chronic infections within 5-10 years compared to individuals suffering from HBV monoinfection. The worldwide trend of HDV infection is decreasing due to HBV vaccination. Pakistan has still high endemicity of HDV. This study was conducted to determine the prevalence of hepatitis D virus infection among the HBV positive patients population and associated risk factors. Methods and materials: Blood samples were collected aseptically in red top vaccutainer from 12679 patients who reported at hepatitis Clinic of Civil Hospital, Karachi, Pakistan, during a period of two years. Demographic data including age, sex and risk behaviour were recorded. All serum samples were screened for the presence of HBsAg by one step ELISA technique and confirmed by PCR for HBV DNA. Samples from HBV positive patients were processed to determine HDV specific antibodies by Sandwich ELISA technique. Results: A total of 2472 (19.5%) patients with symptoms of hepatitis tested positive for presence HBsAg, and HBV DNA out of these HBV positive patients, 1954 were tested for anti HDV, 693 (35.5%) were found to be positive for HDV specific antibodies. HDV infection was most prevalent in patients on both extremes of age, i.e., under 10 years and 71–80 years, slightly higher in females than males and majority had a history of injections (therapeutic) and previous surgery. Conclusion: Our results indicated a very high prevalence of HDV infection among the hepatitis B infected patients population which would suggest that all patients with hepatitis B virus infection should be tested for hepatitis Delta Virus infection to avoid serious complications of the disease like acute fulminant hepatitis, cirrhosis, hepatocellular carcinoma and even death. Mass screening, HBV vaccination campaigns and awareness about the route of spread of the disease must be carried out.

Fast Differentiation of HepaRG Cells Allowing Hepatitis B and Delta Virus Infections.

HepaRG cells are liver bipotent progenitors acquiring hepatocytes features when differentiated in the presence of dimethylsulfoxide (DMSO). Differentiated HepaRG (dHepaRG) are considered the best surrogate model to primary human hepatocytes (PHH) and are susceptible to several hepatotropic viruses, including Hepatitis B Virus (HBV) and Hepatitis Delta Virus (HDV) infection. Despite these advantages, HepaRG cells are not widely used for the study of these two viruses because of their long differentiation process and their rather low and variable infection rates. Here, we tested the use of a cocktail of five chemicals (5C) combined or not with DMSO to accelerate the cells’ differentiation process. We found that NTCP-mediated HDV entry and replication are similar in HepaRG cells cultivated for only 1 week with 5C and DMSO or differentiated with the regular 4-week protocol. However, even though the NTCP-mediated HBV entry process seemed similar, cccDNA and subsequent HBV replication markers were lower in HepaRG cells cultivated for 1 week with 5C and DMSO compared to the regular differentiation protocol. In conclusion, we set up a new procedure allowing fast differentiation and efficient HDV-infection of HepaRG cells and identified differential culture conditions that may allow to decipher the mechanism behind the establishment of the HBV minichromosome.

Long-Term Study of Hepatitis Delta Virus Infection at Secondary Care Centers: The Impact of Viremia on Liver-Related Outcomes.

Hepatitis delta virus (HDV) infection is associated with fast progression to liver cirrhosis and liver complications. Previous studies have, however, been mainly from tertiary care centers, with risk for referral bias toward patients with worse outcomes. Furthermore, the impact of HDV viremia per se on liver-related outcomes is not really known outside the human immunodeficiency virus co-infection setting. We have therefore evaluated the long-term impact of HDV viremia on liver-related outcomes in a nationwide cohort of patients with hepatitis B and D co-infection, cared for at secondary care centers in Sweden. In total, 337 patients with anti-HDV positivity, including 233 patients with HDV RNA viremia and 91 without HDV viremia at baseline, were retrospectively studied, with a mean follow-up of 6.5years (range, 0.5-33.1). The long-term risks for liver-related events (i.e., hepatocellular carcinoma [HCC], hepatic decompensation, or liver-related death/transplantation) were assessed, using Cox regression analysis. The risk for liver-related events and HCC was 3.8-fold and 2.6-fold higher, respectively, in patients with HDV viremia compared with those without viremia, although the latter was not statistically significant. Among patients with HDV viremia with no baseline cirrhosis, the cumulative risk of being free of liver cirrhosis or liver-related events was 81.9% and 64.0% after 5 and 10years of follow-up, respectively. This corresponds to an incidence rate of 0.04 cases per person-year. HDV RNA viremia is associated with a 3.8-fold higher risk for liver-related outcomes. The prognosis was rather poor for patients with HDV viremia without cirrhosis at baseline, but it was nevertheless more benign than previous estimates from tertiary centers. Our findings may be of importance when making decisions about treatment and evaluating potential outcomes of upcoming antivirals against HDV.

Siirt İlinde Yüksek Hepatit Delta Antikoru Sıklığı

Amaç: Eş zamanlı hepatit delta virüs (HDV) enfeksiyonu varlığı kronik hepatit B (KHB) ilişkili karaciğer hastalığının seyrini olumsuz yönde etkilemektedir. Bu çalışmada Siirt ilinde hepatit B virusu (HBV) ile kronik olarak enfekte olan hepatit gelişmiş ve gelişmemiş olgularda delta antikoru (anti-HDV) sıklığının belirlenmesi ve HDV koenfeksiyonu varlığının klinik etkilerinin irdelenmesi amaçlanmıştır. Gereç ve Yöntemler: Bu retrospektif kesitsel çalışmaya Şubat 2017-Şubat 2018 tarihleri arasında Siirt Devlet Hastanesi Enfeksiyon Hastalıkları polikliniğine başvuran Anti-HDV testi bakılmış 288’i HBV ile kronik olarak enfekte, 174’ü KHB gelişmiş toplam 462 olgu dahil edildi. HBV deoksiribonükleik asit (DNA), hepatit B “e” antijeni (HBeAg), alanin aminotransferaz (ALT), HDV ribonükleik asit (RNA) sonuçları ile siroz ve hepatosellüler karsinom (HCC) durumu ile ilgili verilere retrospektif olarak ulaşılmıştır. Çalışmaya alınan hastalar Anti-HDV pozitif (n=128) ve negatif (n=334) olmak üzere iki gruba ayrıldı. KHB, siroz ve HCC sıklığı gruplar arasında karşılaştırılmıştır. Bulgular: Toplam 462 olgunun 205’i (%44,4) kadın, 257’si erkek (%55,6) olup, medyan yaşı 37 (çeyrekler arası aralık (IQR) 26 ila 49) idi. Anti-HDV pozitifliği saptanan toplam 128 (%27,8) olgunun 32’sinde HDV RNA çalışılabilmiş ve 9’unda pozitif olarak saptanmıştır. Çalışmamızda nonsirotik ve sirotik olgulardaki anti-HDV sıklığının sırasıyla %26,2 ve %68,8 olduğu görülmüştür. Anti-HDV pozitif olgularda KHB, siroz ve HCC sıklığının Anti-HDV negatif olgulara göre anlamlı oranda yüksek olduğu görülmüştür (p=0,003, p=0,001, p=0,021). Sonuç: Bu çalışmada elde edilen verilere dayanarak, Siirt ilinde HBV ile enfekte olgularda Anti-HDV sıklığının Türkiye ortalamasının (%5,2) çok üzerinde olduğu ve Anti-HDV pozitif olguların KHB, siroz ve HCC gelişimi açısından Anti-HDV negatif olgulara oranla daha yakın izlem gerektirdiği söylenebilir.

Ten‐year follow‐up of a randomized controlled clinical trial in chronic hepatitis delta

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis. PEG-interferon alpha-2a (PEG-IFNα-2a) is the only effective treatment but its long-term clinical impact is unclear. The aim of this study was to investigate the long-term outcome after 48weeks of pegylated interferon alpha-2a therapy. We performed a retrospective follow-up study of the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-I trial). Patients had received 48weeks of treatment with either PEG-IFNα-2a plus adefovir dipivoxil (ADV) (Group I), PEG-IFNα-2a alone (Group II) or adefovir dipivoxil alone (Group III). Liver-related complications were defined as liver-related death, liver transplantation, liver cancer and hepatic decompensation defined as development of Child-Pugh scores B or C or an increase in Model for End-stage Liver Disease (MELD) scores of five or more points in relation to baseline values. Patients were considered for further analysis when they were retreated with PEG-IFNα-2a. Follow-up data (at least 1 visit beyond post-treatment week 24) were available for 60 patients [Group I, (n=19), Group II (n=20), Group III (n=21)]. Mean time of follow-up was 8.9 (1.6 - 13.4) years. 19 patients were retreated with IFN-based therapy: 42% (n=8) in PEG-IFNα-2a arms and 58% (n=11) in the adefovir only arm. Clinical complications on long-term follow-up occurred in 17 patients and were associated with nonresponse to therapy and baseline cirrhosis. The annual event-free survival rate in patients with cirrhosis vs noncirrhotic patients at year 5 and 10 was 70% vs 91% and 35% vs 76%. Long-term follow-up of a large randomized clinical trial suggests that off-treatment HDV RNA response to PEG-IFNα-2a treatment leads to improved clinical long-term outcome.

SAT385 - Toll-like receptor 7 and 8 agonists as potent inhibitors of hepatitis delta virus infection

SAT385 - Toll-like receptor 7 and 8 agonists as potent inhibitors of hepatitis delta virus infection

Epidemiology, Natural History, and Treatment of Hepatitis Delta Virus Infection in HIV/Hepatitis B Virus Coinfection.

Limited data exist on the prevalence, determinants, and outcomes of hepatitis delta virus (HDV) infection among HIV/hepatitis B virus (HBV)-coinfected persons. This review provides current evidence on the epidemiology, natural history, and treatment of HDV infection in patients with HIV/HBV coinfection and highlights future research needs. Cross-sectional studies in Europe, Africa, South America, and Asia show that the prevalence of HDV among HIV/HBV-coinfected patients ranges from 1.2 to 25%. No studies have evaluated the prevalence of HDV infection among HIV/HBV-coinfected patients in the USA. HDV infection increases the risk of hepatic decompensation and hepatocellular carcinoma among HIV/HBV-coinfected patients. HDV treatment remains limited to pegylated interferon-alpha, which results in sustained virologic response in fewer than 25%. Data on the epidemiology, natural history, and treatment of HDV among HIV/HBV-coinfected persons remain limited. More research is needed to address these knowledge gaps in order to better manage HDV coinfection in HIV/HBV-coinfected patients.