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CC BY-NC-ND 4.0 · Semin Liver Dis 2023; 43(03): 293-304
DOI: 10.1055/a-2133-8614
Review Article

Hepatitis Delta Infection: A Clinical Review

Brian Pearlman
1   Department of Internal Medicine, Wellstar Atlanta Medical Center, Medical College of Georgia, Emory School of Medicine, Atlanta, Georgia
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Erratum to: Hepatitis Delta Infection: A Clinical ReviewSemin Liver Dis 2023; 43(03): e1-e1
DOI: 10.1055/s-0043-1776037

Abstract

First discovered over 40 years ago, the hepatitis delta virus (HDV) is a unique RNA virus, requiring hepatitis B virus (HBV) antigens for its assembly, replication, and transmission. HBV and HDV can be acquired at the same time (coinfection) or HDV infection can occur in persons with chronic HBV (superinfection). Screening guidelines for HDV are inconsistent. While some guidelines recommend universal screening for all people with HBV, others recommend risk-based screening. Estimates of the global HDV prevalence range from 4.5 to 14.6% among persons with HBV; thus, there may be up to 72 million individuals with HDV worldwide. HDV is the most severe form of viral hepatitis. Compared to HBV monoinfection, HDV coinfection increases the risk of cirrhosis, hepatocellular carcinoma, hepatic decompensation, mortality, and necessity for liver transplant. Despite the severity of HDV, there are few treatment options. Pegylated interferon (off-label use) has long been the only available treatment, although bulevirtide is conditionally approved in some European countries. There are many potential treatments in development, but as yet, there are few effective and safe therapies for HDV infection. In conclusion, given the severity of HDV disease and the paucity of treatments, there is a great unmet need for HDV therapies.

Keywords

HDV - hepatitis - HBV - bulevirtide - delta


Publication History

Accepted Manuscript online:
20 July 2023

Article published online:
30 August 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 He LF, Ford E, Purcell RH, London WT, Phillips J, Gerin JL. The size of the hepatitis delta agent. J Med Virol 1989; 27 (01) 31-33
    CrossrefPubMedGoogle Scholar
  • 2 Lempp FA, Ni Y, Urban S. Hepatitis delta virus: insights into a peculiar pathogen and novel treatment options. Nat Rev Gastroenterol Hepatol 2016; 13 (10) 580-589
    CrossrefPubMedGoogle Scholar
  • 3 Urban S, Neumann-Haefelin C, Lampertico P. Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease. Gut 2021; 70 (09) 1782-1794
    CrossrefPubMedGoogle Scholar
  • 4 Lucifora J, Delphin M. Current knowledge on hepatitis delta virus replication. Antiviral Res 2020; 179: 104812
    CrossrefPubMedGoogle Scholar
  • 5 Rizzetto M, Canese MG, Aricò S. et al. Immunofluorescence detection of new antigen-antibody system (delta/anti-delta) associated to hepatitis B virus in liver and in serum of HBsAg carriers. Gut 1977; 18 (12) 997-1003
    CrossrefPubMedGoogle Scholar
  • 6 Alfaiate D, Clément S, Gomes D, Goossens N, Negro F. Chronic hepatitis D and hepatocellular carcinoma: a systematic review and meta-analysis of observational studies. J Hepatol 2020; 73 (03) 533-539
    CrossrefPubMedGoogle Scholar
  • 7 Liao B, Zhang F, Lin S. et al. Epidemiological, clinical and histological characteristics of HBV/HDV co-infection: a retrospective cross-sectional study in Guangdong, China. PLoS One 2014; 9 (12) e115888
    CrossrefPubMedGoogle Scholar
  • 8 Osiowy C, Swidinsky K, Haylock-Jacobs S. et al. Molecular epidemiology and clinical characteristics of hepatitis D virus infection in Canada. JHEP Rep Innov Hepatol 2022; 4 (05) 100461
    CrossrefPubMedGoogle Scholar
  • 9 Chen HY, Shen DT, Ji DZ. et al. Prevalence and burden of hepatitis D virus infection in the global population: a systematic review and meta-analysis. Gut 2019; 68 (03) 512-521
    CrossrefPubMedGoogle Scholar
  • 10 Romeo R, Del Ninno E, Rumi M. et al. A 28-year study of the course of hepatitis delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. Gastroenterology 2009; 136 (05) 1629-1638
    CrossrefPubMedGoogle Scholar
  • 11 Stockdale AJ, Kreuels B, Henrion MYR. et al. The global prevalence of hepatitis D virus infection: systematic review and meta-analysis. J Hepatol 2020; 73 (03) 523-532
    CrossrefPubMedGoogle Scholar
  • 12 World Health Organization (WHO). Hepatitis D Fact Sheet. Geneva, Switzerland: WHO; 2022
    Google Scholar
  • 13 Miao Z, Zhang S, Ou X. et al. Estimating the global prevalence, disease progression, and clinical outcome of hepatitis delta virus infection. J Infect Dis 2020; 221 (10) 1677-1687
    CrossrefPubMedGoogle Scholar
  • 14 Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet 2015; 386 (10003): 1546-1555
    CrossrefPubMedGoogle Scholar
  • 15 Razavi-Shearer D, Dhindsa K, Razavi H. Population adjusted prevalence of hepatitis delta virus in 16 countries. Hepatology 2022; 76: S211
    PubMedGoogle Scholar
  • 16 Kushner T, Serper M, Kaplan DE. Delta hepatitis within the Veterans Affairs medical system in the United States: prevalence, risk factors, and outcomes. J Hepatol 2015; 63 (03) 586-592
    CrossrefPubMedGoogle Scholar
  • 17 Patel EU, Thio CL, Boon D, Thomas DL, Tobian AAR. Prevalence of hepatitis B and hepatitis D virus infections in the United States, 2011-2016. Clin Infect Dis 2019; 69 (04) 709-712
    CrossrefPubMedGoogle Scholar
  • 18 Njei B, Do A, Lim JK. Prevalence of hepatitis delta infection in the United States: National Health and Nutrition Examination Survey, 1999-2012. Hepatology 2016; 64 (02) 681-682
    CrossrefPubMedGoogle Scholar
  • 19 Da BL, Rahman F, Lai WC, Kleiner DE, Heller T, Koh C. Risk factors for delta hepatitis in a North American cohort: who should be screened?. Am J Gastroenterol 2021; 116 (01) 206-209
    CrossrefPubMedGoogle Scholar
  • 20 Terrault NA, Lok ASF, McMahon BJ. et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67 (04) 1560-1599
    CrossrefPubMedGoogle Scholar
  • 21 Da BL, Heller T, Koh C. Hepatitis D infection: from initial discovery to current investigational therapies. Gastroenterol Rep (Oxf) 2019; 7 (04) 231-245
    CrossrefPubMedGoogle Scholar
  • 22 Papatheodoridi M, Papatheodoridis GV. Is hepatitis delta underestimated?. Liver Int 2021; 41 (Suppl. 01) 38-44
    CrossrefPubMedGoogle Scholar
  • 23 Palom A, Rando-Segura A, Barciela M. et al. Low adherence to guidelines recommendation for testing hepatitis D in HBsAg positive patients leads to a high rate of undiagnosis. Hepatol 2021; 74: 148A-149A
    PubMedGoogle Scholar
  • 24 Safaie P, Razeghi S, Rouster SD, Privitera I, Sherman KE. Hepatitis D diagnostics: utilization and testing in the United States. Virus Res 2018; 250: 114-117
    CrossrefPubMedGoogle Scholar
  • 25 European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017; 67 (02) 370-398
    CrossrefPubMedGoogle Scholar
  • 26 Sarin SK, Kumar M, Lau GK. et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016; 10 (01) 1-98
    CrossrefPubMedGoogle Scholar
  • 27 Wedemeyer H, Manns MP. Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. Nat Rev Gastroenterol Hepatol 2010; 7 (01) 31-40
    CrossrefPubMedGoogle Scholar
  • 28 Wedemeyer H, Negro F. Devil hepatitis D: an orphan disease or largely underdiagnosed?. Gut 2019; 68 (03) 381-382
    CrossrefPubMedGoogle Scholar
  • 29 Miao Z, Pan Q. Revisiting the estimation of hepatitis D global prevalence. J Hepatol 2020; 73 (05) 1279-1280
    CrossrefPubMedGoogle Scholar
  • 30 Stockdale AJ, Kreuels B, Henrion MRY, Giorgi E, Kyomuhangi I, Geretti AM. Hepatitis D prevalence: problems with extrapolation to global population estimates. Gut 2020; 69 (02) 396-397
    CrossrefPubMedGoogle Scholar
  • 31 Değertekin H, Yalçin K, Yakut M, Yurdaydin C. Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta-analysis. Liver Int 2008; 28 (04) 494-498
    CrossrefPubMedGoogle Scholar
  • 32 Fong TL, Lee BT, Chang M. et al. High prevalence of chronic viral hepatitis and liver fibrosis among Mongols in Southern California. Dig Dis Sci 2021; 66 (08) 2833-2839
    CrossrefPubMedGoogle Scholar
  • 33 Le Gal F, Brichler S, Drugan T. et al. Genetic diversity and worldwide distribution of the delta virus genus: a study of 2,152 clinical strains. Hepatology 2017; 66 (06) 1826-1841
    CrossrefPubMedGoogle Scholar
  • 34 Su CW, Huang YH, Huo TI. et al. Genotypes and viremia of hepatitis B and D viruses are associated with outcomes of chronic hepatitis D patients. Gastroenterology 2006; 130 (06) 1625-1635
    CrossrefPubMedGoogle Scholar
  • 35 Gomes-Gouvêa MS, Soares MCP, Bensabath G. et al. Hepatitis B virus and hepatitis delta virus genotypes in outbreaks of fulminant hepatitis (Labrea black fever) in the western Brazilian Amazon region. J Gen Virol 2009; 90 (Pt 11): 2638-2643
    CrossrefPubMedGoogle Scholar
  • 36 Melo Da Silva E, Kay A, Lobato C. et al. Non-F HBV/HDV-3 coinfection is associated with severe liver disease in Western Brazilian Amazon. J Med Virol 2019; 91 (06) 1081-1086
    CrossrefPubMedGoogle Scholar
  • 37 Hughes SA, Wedemeyer H, Harrison PM. Hepatitis delta virus. Lancet 2011; 378 (9785) 73-85
    CrossrefPubMedGoogle Scholar
  • 38 Sagnelli C, Pisaturo M, Curatolo C, Codella AV, Coppola N, Sagnelli E. Hepatitis B virus/hepatitis D virus epidemiology: changes over time and possible future influence of the SARS-CoV-2 pandemic. World J Gastroenterol 2021; 27 (42) 7271-7284
    CrossrefPubMedGoogle Scholar
  • 39 Chen PJ, Kalpana G, Goldberg J. et al. Structure and replication of the genome of the hepatitis delta virus. Proc Natl Acad Sci U S A 1986; 83 (22) 8774-8778
    CrossrefPubMedGoogle Scholar
  • 40 Kos A, Dijkema R, Arnberg AC, van der Meide PH, Schellekens H. The hepatitis delta (delta) virus possesses a circular RNA. Nature 1986; 323 (6088) 558-560
    CrossrefPubMedGoogle Scholar
  • 41 Wang KS, Choo QL, Weiner AJ. et al. Structure, sequence and expression of the hepatitis delta (delta) viral genome. Nature 1986; 323 (6088) 508-514
    CrossrefPubMedGoogle Scholar
  • 42 Abbas Z, Afzal R. Life cycle and pathogenesis of hepatitis D virus: a review. World J Hepatol 2013; 5 (12) 666-675
    CrossrefPubMedGoogle Scholar
  • 43 Chang FL, Chen PJ, Tu SJ, Wang CJ, Chen DS. The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus. Proc Natl Acad Sci U S A 1991; 88 (19) 8490-8494
    CrossrefPubMedGoogle Scholar
  • 44 Chao M, Hsieh SY, Taylor J. Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of self-limiting genome replication. J Virol 1990; 64 (10) 5066-5069
    CrossrefPubMedGoogle Scholar
  • 45 Hsieh SY, Chao M, Coates L, Taylor J. Hepatitis delta virus genome replication: a polyadenylated mRNA for delta antigen. J Virol 1990; 64 (07) 3192-3198
    CrossrefPubMedGoogle Scholar
  • 46 Kuo MY, Chao M, Taylor J. Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen. J Virol 1989; 63 (05) 1945-1950
    CrossrefPubMedGoogle Scholar
  • 47 Casey JL. Control of ADAR1 editing of hepatitis delta virus RNAs. Curr Top Microbiol Immunol 2012; 353: 123-143
    PubMedGoogle Scholar
  • 48 Casey JL, Gerin JL. Hepatitis D virus RNA editing: specific modification of adenosine in the antigenomic RNA. J Virol 1995; 69 (12) 7593-7600
    CrossrefPubMedGoogle Scholar
  • 49 Sato S, Cornillez-Ty C, Lazinski DW. By inhibiting replication, the large hepatitis delta antigen can indirectly regulate amber/W editing and its own expression. J Virol 2004; 78 (15) 8120-8134
    CrossrefPubMedGoogle Scholar
  • 50 Sato S, Wong SK, Lazinski DW. Hepatitis delta virus minimal substrates competent for editing by ADAR1 and ADAR2. J Virol 2001; 75 (18) 8547-8555
    CrossrefPubMedGoogle Scholar
  • 51 Wong SK, Lazinski DW. Replicating hepatitis delta virus RNA is edited in the nucleus by the small form of ADAR1. Proc Natl Acad Sci U S A 2002; 99 (23) 15118-15123
    CrossrefPubMedGoogle Scholar
  • 52 Glenn JS, Watson JA, Havel CM, White JM. Identification of a prenylation site in delta virus large antigen. Science 1992; 256 (5061) 1331-1333
    CrossrefPubMedGoogle Scholar
  • 53 Lee CZ, Chen PJ, Lai MM, Chen DS. Isoprenylation of large hepatitis delta antigen is necessary but not sufficient for hepatitis delta virus assembly. Virology 1994; 199 (01) 169-175
    CrossrefPubMedGoogle Scholar
  • 54 Zhang Z, Urban S. New insights into HDV persistence: the role of interferon response and implications for upcoming novel therapies. J Hepatol 2021; 74 (03) 686-699
    CrossrefPubMedGoogle Scholar
  • 55 Scheller L, Hilgard G, Anastasiou O. et al. Poor clinical and virological outcome of nucleos(t)ide analogue monotherapy in HBV/HDV co-infected patients. Medicine (Baltimore) 2021; 100 (28) e26571
    CrossrefPubMedGoogle Scholar
  • 56 Rizzetto M. Hepatitis D virus: introduction and epidemiology. Cold Spring Harb Perspect Med 2015; 5 (07) a021576
    CrossrefPubMedGoogle Scholar
  • 57 Sellier PO, Maylin S, Brichler S. et al. Hepatitis B virus-hepatitis D virus mother-to-child co-transmission: a retrospective study in a developed country. Liver Int 2018; 38 (04) 611-618
    CrossrefPubMedGoogle Scholar
  • 58 Negro F. Hepatitis D virus coinfection and superinfection. Cold Spring Harb Perspect Med 2014; 4 (11) a021550
    CrossrefPubMedGoogle Scholar
  • 59 Rizzetto M. Hepatitis D: virology, clinical and epidemiological aspects. Acta Gastroenterol Belg 2000; 63 (02) 221-224
    PubMedGoogle Scholar
  • 60 Pondé RAA. The serological markers of acute infection with hepatitis A, B, C, D, E and G viruses revisited. Arch Virol 2017; 162 (12) 3587-3602
    CrossrefPubMedGoogle Scholar
  • 61 Muhammad H, Tehreem A, Hammami MB, Ting PS, Idilman R, Gurakar A. Hepatitis D virus and liver transplantation: indications and outcomes. World J Hepatol 2021; 13 (03) 291-299
    CrossrefPubMedGoogle Scholar
  • 62 Niro GA, Smedile A, Ippolito AM. et al. Outcome of chronic delta hepatitis in Italy: a long-term cohort study. J Hepatol 2010; 53 (05) 834-840
    CrossrefPubMedGoogle Scholar
  • 63 Lutterkort GL, Wranke A, Yurdaydin C. et al. Non-invasive fibrosis score for hepatitis delta. Liver Int 2017; 37 (02) 196-204
    CrossrefPubMedGoogle Scholar
  • 64 Calle Serrano B, Großhennig A, Homs M. et al. Development and evaluation of a baseline-event-anticipation score for hepatitis delta. J Viral Hepat 2014; 21 (11) e154-e163
    CrossrefPubMedGoogle Scholar
  • 65 Palom A, Rodríguez-Tajes S, Navascués CA. et al. Long-term clinical outcomes in patients with chronic hepatitis delta: the role of persistent viraemia. Aliment Pharmacol Ther 2020; 51 (01) 158-166
    CrossrefPubMedGoogle Scholar
  • 66 Palom A, Sopena S, Riveiro-Barciela M. et al. One-quarter of chronic hepatitis D patients reach HDV-RNA decline or undetectability during the natural course of the disease. Aliment Pharmacol Ther 2021; 54 (04) 462-469
    CrossrefPubMedGoogle Scholar
  • 67 Kamal H, Aleman S, Consortium DS. D-SOLVE Consortium. Natural history of untreated HDV patients: always a progressive disease?. Liver Int 2022; DOI: 10.1111/liv.15467.
    CrossrefPubMedGoogle Scholar
  • 68 Kamal H, Westman G, Falconer K. et al. Long-term study of hepatitis delta virus Infection at secondary care centers: the impact of viremia on liver-related outcomes. Hepatology 2020; 72 (04) 1177-1190
    CrossrefPubMedGoogle Scholar
  • 69 Cheung A, Kwo P. Viral hepatitis other than A, B, and C: evaluation and management. Clin Liver Dis 2020; 24 (03) 405-419
    CrossrefPubMedGoogle Scholar
  • 70 Chen LY, Pang XY, Goyal H, Yang RX, Xu HG. Hepatitis D: challenges in the estimation of true prevalence and laboratory diagnosis. Gut Pathog 2021; 13 (01) 66
    CrossrefPubMedGoogle Scholar
  • 71 Olivero A, Smedile A. Hepatitis delta virus diagnosis. Semin Liver Dis 2012; 32 (03) 220-227
    Article in Thieme ConnectPubMedGoogle Scholar
  • 72 Wranke A, Heidrich B, Ernst S. et al; HIDIT-2 Study Group. Anti-HDV IgM as a marker of disease activity in hepatitis delta. PLoS One 2014; 9 (07) e101002
    CrossrefPubMedGoogle Scholar
  • 73 Zachou K, Yurdaydin C, Drebber U. et al; HIDT-1 Study Group. Quantitative HBsAg and HDV-RNA levels in chronic delta hepatitis. Liver Int 2010; 30 (03) 430-437
    CrossrefPubMedGoogle Scholar
  • 74 Staub F, Tournoux-Facon C, Roumy J. et al. Liver fibrosis staging with contrast-enhanced ultrasonography: prospective multicenter study compared with METAVIR scoring. Eur Radiol 2009; 19 (08) 1991-1997
    CrossrefPubMedGoogle Scholar
  • 75 Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med 2001; 344 (07) 495-500
    CrossrefPubMedGoogle Scholar
  • 76 Alves Vasconcelos MP, DallÁcqua DV, Wedemeyer H, Witkin SS, Mendes-Corrêa MC, Villalobos-Salcedo JM. Noninvasive models for predicting liver fibrosis in individuals with hepatitis D virus/hepatitis B virus coinfection in the Brazilian Amazon region. Am J Trop Med Hyg 2020; 103 (01) 169-174
    CrossrefPubMedGoogle Scholar
  • 77 Da BL, Surana P, Takyar V, Kleiner DE, Heller T, Koh C. Vibration-controlled transient elastography for the detection of cirrhosis in chronic hepatitis D infection. J Viral Hepat 2020; 27 (04) 428-436
    CrossrefPubMedGoogle Scholar
  • 78 Takyar V, Surana P, Kleiner DE. et al. Noninvasive markers for staging fibrosis in chronic delta hepatitis. Aliment Pharmacol Ther 2017; 45 (01) 127-138
    CrossrefPubMedGoogle Scholar
  • 79 Kalkan Ç, Yılmaz Y, Erdoğan BD. et al. Non-invasive fibrosis markers for assessment of liver fibrosis in chronic hepatitis delta. J Viral Hepat 2023; 30 (05) 406-416
    CrossrefPubMedGoogle Scholar
  • 80 Sung H, Ferlay J, Siegel RL. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71 (03) 209-249
    Google Scholar
  • 81 Puigvehí M, Moctezuma-Velázquez C, Villanueva A, Llovet JM. The oncogenic role of hepatitis delta virus in hepatocellular carcinoma. JHEP Rep Innov Hepatol 2019; 1 (02) 120-130
    CrossrefPubMedGoogle Scholar
  • 82 Asselah T, Loureiro D, Tout I. et al. Future treatments for hepatitis delta virus infection. Liver Int 2020; 40 (Suppl. 01) 54-60
    CrossrefPubMedGoogle Scholar
  • 83 Yurdaydin C, Abbas Z, Buti M. et al; Hepatitis Delta International Network (HDIN). Treating chronic hepatitis delta: the need for surrogate markers of treatment efficacy. J Hepatol 2019; 70 (05) 1008-1015
    CrossrefPubMedGoogle Scholar
  • 84 Niro GA, Ciancio A, Gaeta GB. et al. Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta. Hepatology 2006; 44 (03) 713-720
    CrossrefPubMedGoogle Scholar
  • 85 Heidrich B, Yurdaydın C, Kabaçam G. et al; HIDIT-1 Study Group. Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta. Hepatology 2014; 60 (01) 87-97
    CrossrefPubMedGoogle Scholar
  • 86 Etzion O, Hamid S, Lurie Y. et al. Treatment of chronic hepatitis D with peginterferon lambda-the phase 2 LIMT-1 clinical trial. Hepatology 2023; 77 (06) 2093-2103
    CrossrefPubMedGoogle Scholar
  • 87 Duehren S. Peginterferon lambda (IFN-λ) combined with lonafarnib diminished triphasic HDV kinetic pattern seen under IFN-λ monotherapy: the LIFT-1 study. Presented at the International Liver Congress, London, UK, June 22–26, 2022
    PubMedGoogle Scholar
  • 88 Asselah T, Arama S, Bogomolov P. et al. Safety and efficacy of bulevirtide monotherapy and in combination with peginterferon alpha-2a in patients with chronic hepatitis delta: 24 weeks interim data of MYR204 Phase 2b study. Presented at the Digital International Liver Conference, June 23–26, 2021: Abstract 2717
    PubMedGoogle Scholar
  • 89 Wedemeyer H, Schöneweis K, Bogomolov P. et al. Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial. Lancet Infect Dis 2023; 23 (01) 117-129
    CrossrefPubMedGoogle Scholar
  • 90 Wedemeyer H, Aleman S, Brunetto M. et al. Efficacy and safety of bulevirtide monotherapy given at 2 mg or 10 mg dose level once daily OFR treatment of chronic hepatitis delta: week 48 primary end point results from a phase 3 randomized, multicenter, parallel design study. J Hepatol 2022; 77: S4
    CrossrefPubMedGoogle Scholar
  • 91 De Ledinghen V, Hermabessiere P, Metivier S. et al. Bulevirtide, with or without peg-interferon, in HDV infected patients in a real-life setting, two-year results from the French multicenter early access program. Hepatol 2022; 76: S26-S27
    PubMedGoogle Scholar
  • 92 Anonymous. Hepcludex. Summary of Product Characteristics. Carrigtwohill, County Cork: Gilead Sciences Ireland UC. 2021
    Google Scholar
  • 93 Koh C, Canini L, Dahari H. et al. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial. Lancet Infect Dis 2015; 15 (10) 1167-1174
    CrossrefPubMedGoogle Scholar
  • 94 Yurdaydin C, Keskin O, Yurdcu E. et al. A phase 2 dose-finding study of lonafarnib and ritonavir with or without interferon alpha for chronic delta hepatitis. Hepatology 2022; 75 (06) 1551-1565
    CrossrefPubMedGoogle Scholar
  • 95 Bazinet M, Pântea V, Cebotarescu V. et al. Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol 2017; 2 (12) 877-889
    CrossrefPubMedGoogle Scholar
  • 96 Bazinet M, Pântea V, Cebotarescu V. et al. Persistent control of hepatitis B virus and hepatitis delta virus infection following REP 2139-Ca and pegylated interferon therapy in chronic hepatitis B virus/hepatitis delta virus coinfection. Hepatol Commun 2020; 5 (02) 189-202
    CrossrefPubMedGoogle Scholar
  • 97 Lok AS, Negro F, Asselah T, Farci P, Rizzetto M. Endpoints and new options for treatment of chronic hepatitis D. Hepatology 2021; 74 (06) 3479-3485
    CrossrefPubMedGoogle Scholar
  • 98 Sandmann L, Cornberg M. Experimental drugs for the treatment of hepatitis D. J Exp Pharmacol 2021; 13: 461-468
    CrossrefPubMedGoogle Scholar