Hepatitis D future or investigational therapies: Difference between revisions
Joao Silva (talk | contribs) No edit summary |
m (Bot: Removing from Primary care) |
||
| (16 intermediate revisions by 3 users not shown) | |||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
Potential targets for [[antiviral]] therapy of [[HDV]] include drugs that interfere with [[translation|postranslational]] modification and [[viral]] assembly. New drugs, such as [[prenylation]] inhibitors, [[HBV]] entry inhibitors, and new forms of [[interferons]] are currently being studied and tested for the treatment of hepatitis D, with better [[efficacy]] and tolerability.<ref name="pmid23242761">{{cite journal| author=Heidrich B, Manns MP, Wedemeyer H| title=Treatment options for hepatitis delta virus infection. | journal=Curr Infect Dis Rep | year= 2013 | volume= 15 | issue= 1 | pages= 31-8 | pmid=23242761 | doi=10.1007/s11908-012-0307-z | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23242761 }} </ref><ref name="pmid12897208">{{cite journal| author=Bordier BB, Ohkanda J, Liu P, Lee SY, Salazar FH, Marion PL et al.| title=In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. | journal=J Clin Invest | year= 2003 | volume= 112 | issue= 3 | pages= 407-14 | pmid=12897208 | doi=10.1172/JCI17704 | pmc=PMC166292 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12897208 }} </ref><ref name="pmid18297057">{{cite journal| author=Petersen J, Dandri M, Mier W, Lütgehetmann M, Volz T, von Weizsäcker F et al.| title=Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. | journal=Nat Biotechnol | year= 2008 | volume= 26 | issue= 3 | pages= 335-41 | pmid=18297057 | doi=10.1038/nbt1389 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18297057 }} </ref><ref name="pmid22031488">{{cite journal| author=Lütgehetmann M, Mancke LV, Volz T, Helbig M, Allweiss L, Bornscheuer T et al.| title=Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation. | journal=Hepatology | year= 2012 | volume= 55 | issue= 3 | pages= 685-94 | pmid=22031488 | doi=10.1002/hep.24758 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22031488 }} </ref> | |||
==Future or Investigational Therapies== | ==Future or Investigational Therapies== | ||
Although the lack of [[viral]] [[enzymes]] represents a challenge for the development of [[antiviral drugs]], the [[life cycle]] of [[HDV]] relies deeply on [[translation|postranslational]] modification of [[proteins]] and [[viral]] assembly. Therefore, these two stages are potential targets for [[antiviral drugs]].<ref name="pmid23242761">{{cite journal| author=Heidrich B, Manns MP, Wedemeyer H| title=Treatment options for hepatitis delta virus infection. | journal=Curr Infect Dis Rep | year= 2013 | volume= 15 | issue= 1 | pages= 31-8 | pmid=23242761 | doi=10.1007/s11908-012-0307-z | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23242761 }} </ref> | |||
[[Prenylation]] inhibitors are one example of [[antiviral drugs]] that target [[HDV]] [[replication]] cycle. These drugs have been used in cancer treatments, and are now being studied in therapies for [[hepatitis D]].<ref name="pmid12897208">{{cite journal| author=Bordier BB, Ohkanda J, Liu P, Lee SY, Salazar FH, Marion PL et al.| title=In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. | journal=J Clin Invest | year= 2003 | volume= 112 | issue= 3 | pages= 407-14 | pmid=12897208 | doi=10.1172/JCI17704 | pmc=PMC166292 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12897208 }} </ref> | |||
The dependence of [[HDV]] on previous, or simultaneous [[infection]] of [[hepatocytes]] by [[HBV]], makes this another potential target for [[antiviral]] treatments. Myrcludex B (entry inhibitor of HBV) was shown to inhibit [[infection]] of the host cell by [[HBV]] in ''in vitro'' models and ''in vivo'' mice, consequently preventing [[infection]] by [[HDV]]. The drug is currently in the trial phase.<ref name="pmid18297057">{{cite journal| author=Petersen J, Dandri M, Mier W, Lütgehetmann M, Volz T, von Weizsäcker F et al.| title=Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. | journal=Nat Biotechnol | year= 2008 | volume= 26 | issue= 3 | pages= 335-41 | pmid=18297057 | doi=10.1038/nbt1389 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18297057 }} </ref><ref name="pmid22031488">{{cite journal| author=Lütgehetmann M, Mancke LV, Volz T, Helbig M, Allweiss L, Bornscheuer T et al.| title=Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation. | journal=Hepatology | year= 2012 | volume= 55 | issue= 3 | pages= 685-94 | pmid=22031488 | doi=10.1002/hep.24758 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22031488 }} </ref> | |||
Other potential [[antiviral]] target is the optimization of current treatments, such as [[interferons]], or TLR agonists. A commonly used [[interferon]] is the type I [[interferon]], which has receptors in different cells across the body, leading to its many side-effects. Other potential [[interferon]], with less side effects, is the interferon-lambda. Because its receptors are less expressed in other cells, interferon-lambda, already being tested for [[hepatitis C]], represents an alternative treatment for patients with [[hepatitis B]] and [[hepatitis D|delta]].<ref name="pmid20564352">{{cite journal| author=Muir AJ, Shiffman ML, Zaman A, Yoffe B, de la Torre A, Flamm S et al.| title=Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. | journal=Hepatology | year= 2010 | volume= 52 | issue= 3 | pages= 822-32 | pmid=20564352 | doi=10.1002/hep.23743 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20564352 }} </ref> | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
{{WH}} | |||
{{WS}} | |||
[[Category:Hepatitis|D]] | [[Category:Hepatitis|D]] | ||
[[Category:Viruses]] | [[Category:Viruses]] | ||
[[Category:Gastroenterology]] | [[Category:Gastroenterology]] | ||
[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Emergency mdicine]] | |||
[[Category:Up-To-Date]] | |||
[[Category:Infectious disease]] | |||
[[Category:Hepatology]] | |||
Latest revision as of 22:06, 29 July 2020
|
Hepatitis D |
|
Diagnosis |
|
Treatment |
|
Hepatitis D future or investigational therapies On the Web |
|
American Roentgen Ray Society Images of Hepatitis D future or investigational therapies |
|
Risk calculators and risk factors for Hepatitis D future or investigational therapies |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2] Jolanta Marszalek, M.D. [3]
Overview
Potential targets for antiviral therapy of HDV include drugs that interfere with postranslational modification and viral assembly. New drugs, such as prenylation inhibitors, HBV entry inhibitors, and new forms of interferons are currently being studied and tested for the treatment of hepatitis D, with better efficacy and tolerability.[1][2][3][4]
Future or Investigational Therapies
Although the lack of viral enzymes represents a challenge for the development of antiviral drugs, the life cycle of HDV relies deeply on postranslational modification of proteins and viral assembly. Therefore, these two stages are potential targets for antiviral drugs.[1]
Prenylation inhibitors are one example of antiviral drugs that target HDV replication cycle. These drugs have been used in cancer treatments, and are now being studied in therapies for hepatitis D.[2]
The dependence of HDV on previous, or simultaneous infection of hepatocytes by HBV, makes this another potential target for antiviral treatments. Myrcludex B (entry inhibitor of HBV) was shown to inhibit infection of the host cell by HBV in in vitro models and in vivo mice, consequently preventing infection by HDV. The drug is currently in the trial phase.[3][4]
Other potential antiviral target is the optimization of current treatments, such as interferons, or TLR agonists. A commonly used interferon is the type I interferon, which has receptors in different cells across the body, leading to its many side-effects. Other potential interferon, with less side effects, is the interferon-lambda. Because its receptors are less expressed in other cells, interferon-lambda, already being tested for hepatitis C, represents an alternative treatment for patients with hepatitis B and delta.[5]
References
- ↑ 1.0 1.1 Heidrich B, Manns MP, Wedemeyer H (2013). "Treatment options for hepatitis delta virus infection". Curr Infect Dis Rep. 15 (1): 31–8. doi:10.1007/s11908-012-0307-z. PMID 23242761.
- ↑ 2.0 2.1 Bordier BB, Ohkanda J, Liu P, Lee SY, Salazar FH, Marion PL; et al. (2003). "In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus". J Clin Invest. 112 (3): 407–14. doi:10.1172/JCI17704. PMC 166292. PMID 12897208.
- ↑ 3.0 3.1 Petersen J, Dandri M, Mier W, Lütgehetmann M, Volz T, von Weizsäcker F; et al. (2008). "Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein". Nat Biotechnol. 26 (3): 335–41. doi:10.1038/nbt1389. PMID 18297057.
- ↑ 4.0 4.1 Lütgehetmann M, Mancke LV, Volz T, Helbig M, Allweiss L, Bornscheuer T; et al. (2012). "Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation". Hepatology. 55 (3): 685–94. doi:10.1002/hep.24758. PMID 22031488.
- ↑ Muir AJ, Shiffman ML, Zaman A, Yoffe B, de la Torre A, Flamm S; et al. (2010). "Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection". Hepatology. 52 (3): 822–32. doi:10.1002/hep.23743. PMID 20564352.