Hepatitis D medical therapy: Difference between revisions
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==Medical Therapy== | ==Medical Therapy== | ||
The goal of treatment in hepatitis D is the clearance of [[HDV]] and [[HBV]] helper virus. The complexity of the treatment resides in the need to address both [[viruses]], and in the simplicity of [[HDV]]. The fact that [[HDV]] uses host cell's [[enzymes]] for its replication, limits the number of targets for therapeutic agents.<ref name="HeidrichManns2012">{{cite journal|last1=Heidrich|first1=Benjamin|last2=Manns|first2=Michael P.|last3=Wedemeyer|first3=Heiner|title=Treatment Options for Hepatitis Delta Virus Infection|journal=Current Infectious Disease Reports|volume=15|issue=1|year=2012|pages=31–38|issn=1523-3847|doi=10.1007/s11908-012-0307-z}}</ref> | The goal of treatment in [[hepatitis D]] is the clearance of [[HDV]] and [[HBV]] helper virus. The complexity of the treatment resides in the need to address both [[viruses]], and in the simplicity of [[HDV]]. The fact that [[HDV]] uses host cell's [[enzymes]] for its [[replication]], limits the number of targets for therapeutic agents.<ref name="HeidrichManns2012">{{cite journal|last1=Heidrich|first1=Benjamin|last2=Manns|first2=Michael P.|last3=Wedemeyer|first3=Heiner|title=Treatment Options for Hepatitis Delta Virus Infection|journal=Current Infectious Disease Reports|volume=15|issue=1|year=2012|pages=31–38|issn=1523-3847|doi=10.1007/s11908-012-0307-z}}</ref> | ||
[[Immunosuppressive]] agents do not have any effect on [[hepatitis D]].<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref><ref name="pmid10535887">{{cite journal| author=Lau DT, Kleiner DE, Park Y, Di Bisceglie AM, Hoofnagle JH| title=Resolution of chronic delta hepatitis after 12 years of interferon alfa therapy. | journal=Gastroenterology | year= 1999 | volume= 117 | issue= 5 | pages= 1229-33 | pmid=10535887 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10535887 }} </ref> | [[Immunosuppressive]] agents do not have any effect on [[hepatitis D]].<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref><ref name="pmid10535887">{{cite journal| author=Lau DT, Kleiner DE, Park Y, Di Bisceglie AM, Hoofnagle JH| title=Resolution of chronic delta hepatitis after 12 years of interferon alfa therapy. | journal=Gastroenterology | year= 1999 | volume= 117 | issue= 5 | pages= 1229-33 | pmid=10535887 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10535887 }} </ref> | ||
===Interferon-α=== | ===Interferon-α=== | ||
[[Interferon-α]] is the only drug that has shown [[antiviral]] activity against [[HDV]]. Both forms of the drug (conventional and pegylated) are able to inhibit [[HDV]] replication cycle. The effect of [[interferon]] is considered to be | [[Interferon-α]] is the only drug that has shown [[antiviral]] activity against [[HDV]]. Both forms of the drug (conventional and pegylated) are able to inhibit [[HDV]] [[replication]] cycle. The effect of [[interferon]] is considered to be an indirect one, possibly via an effect on the helper [[hepadnavirus]] and/or on the [[immune response]].<ref name="HeidrichManns2012">{{cite journal|last1=Heidrich|first1=Benjamin|last2=Manns|first2=Michael P.|last3=Wedemeyer|first3=Heiner|title=Treatment Options for Hepatitis Delta Virus Infection|journal=Current Infectious Disease Reports|volume=15|issue=1|year=2012|pages=31–38|issn=1523-3847|doi=10.1007/s11908-012-0307-z}}</ref><ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref><ref name="FarciMandas1994">{{cite journal|last1=Farci|first1=Patrizia|last2=Mandas|first2=Antonella|last3=Coiana|first3=Alessandra|last4=Lai|first4=Maria Eliana|last5=Desmet|first5=Valeer|last6=Van Eyken|first6=Peter|last7=Gibo|first7=Yukio|last8=aruso|first8=Luciano|last9=Scaccabarozzi|first9=Sergio|last10=Criscuolo|first10=Domenico|last11=Ryff|first11=Jean-Charles|last12=Balestrieri|first12=Angelo|title=Treatment of Chronic Hepatitis D with Interferon Alfa-2a|journal=New England Journal of Medicine|volume=330|issue=2|year=1994|pages=88–94|issn=0028-4793|doi=10.1056/NEJM199401133300202}}</ref> | ||
For infected patients, the following doses have yielded remission | For some [[infected]] patients, the following doses have yielded remission of the disease:<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref><ref name="pmid10535887">{{cite journal| author=Lau DT, Kleiner DE, Park Y, Di Bisceglie AM, Hoofnagle JH| title=Resolution of chronic delta hepatitis after 12 years of interferon alfa therapy. | journal=Gastroenterology | year= 1999 | volume= 117 | issue= 5 | pages= 1229-33 | pmid=10535887 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10535887 }} </ref> | ||
*'''9 million units three times a week, for 12 months''' | *'''9 million units three times a week, for 12 months''' | ||
*'''5 million units daily for up to 12 months''' | *'''5 million units daily for up to 12 months''' | ||
However, most patients remained positive for HDV RNA, despite the improved disease conditions.<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref> | However, most patients remained positive for HDV [[RNA]], despite the improved disease conditions.<ref name=WHO>{{cite web | title = Hepatitis D Prevention and treatment | url = http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html }}</ref> | ||
Even with some discrepancies among studies, relating to dose, form of administration, and treatment duration with [[interferon-α]]:<ref name="FarciRoskams2004">{{cite journal|last1=Farci|first1=Patrizia|last2=Roskams|first2=Tania|last3=Chessa|first3=Luchino|last4=Peddis|first4=Giovanna|last5=Mazzoleni|first5=Anna Paola|last6=Scioscia|first6=Rosetta|last7=Serra|first7=Giancarlo|last8=Lai|first8=Maria Eliana|last9=Loy|first9=Maurizio|last10=Caruso|first10=Luciano|title=Long-term benefit of interferon α therapy of chronic hepatitis D: regression of advanced hepatic fibrosis|journal=Gastroenterology|volume=126|issue=7|year=2004|pages=1740–1749|issn=00165085|doi=10.1053/j.gastro.2004.03.017}}</ref><ref name="pmid15188169">{{cite journal| author=Farci P, Roskams T, Chessa L, Peddis G, Mazzoleni AP, Scioscia R et al.| title=Long-term benefit of interferon alpha therapy of chronic hepatitis D: regression of advanced hepatic fibrosis. | journal=Gastroenterology | year= 2004 | volume= 126 | issue= 7 | pages= 1740-9 | pmid=15188169 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15188169 }} </ref> | |||
*25-40% of patients showed sustained response to treatment 1 to 2 years after therapy. | *25-40% of patients showed sustained response to treatment, 1 to 2 years after therapy. | ||
*According to the HIDIT I trial, about 28% of the patients who were treated with '''180 μg of pegylated interpheron-α/week''', for 48 weeks, were cured. When combined with [[adefovir]], treatment caused a greater decline in the [[HBsAg]] levels. | *According to the HIDIT I trial, about 28% of the patients who were treated with '''180 μg of pegylated interpheron-α/week''', for 48 weeks, were cured. When combined with [[adefovir]], treatment caused a greater decline in the [[HBsAg]] levels. | ||
*Patients treated with higher doses of [[interferon-α]] showed better outcomes than those treated with lower doses of [[interferon]]. | *Patients treated with higher doses of [[interferon-α]] showed better outcomes than those treated with lower doses of [[interferon]]. | ||
*Higher doses were associated with a decrease of [[HBsAg]], [[RNA]], inflammatory activity, and [[fibrosis]]. | *Higher doses were associated with a decrease of [[HBsAg]], [[RNA]], [[inflammatory]] activity, and [[fibrosis]]. | ||
*Prolonged therapies have shown better response rates, however, it is not clear which patients should stop and which should continue the treatment after the first year. | *Prolonged therapies have shown better response rates, however, it is not clear which patients should stop and which should continue the treatment after the first year. | ||
*One study with prolonged treatment for 12 years induced clearance of HDV [[RNA]] | *One study with prolonged treatment for 12 years induced clearance of [[HDV]] [[RNA]] and [[HBsAg]], as well as regression of [[fibrosis]]. | ||
Treatment depends on the severity of the disease:<ref name="pmid21511329">{{cite journal| author=Hughes SA, Wedemeyer H, Harrison PM| title=Hepatitis delta virus. | journal=Lancet | year= 2011 | volume= 378 | issue= 9785 | pages= 73-85 | pmid=21511329 | doi=10.1016/S0140-6736(10)61931-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21511329 }} </ref> | Treatment depends on the severity of the disease:<ref name="pmid21511329">{{cite journal| author=Hughes SA, Wedemeyer H, Harrison PM| title=Hepatitis delta virus. | journal=Lancet | year= 2011 | volume= 378 | issue= 9785 | pages= 73-85 | pmid=21511329 | doi=10.1016/S0140-6736(10)61931-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21511329 }} </ref> | ||
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* Mild disease may not require immediate [[antiviral]] treatment | * Mild disease may not require immediate [[antiviral]] treatment | ||
Patients infected with [[HDV]] [[genotype]] 1 have worst | Patients infected with [[HDV]] [[genotype]] 1 have worst responses to pegylated [[interferon]] than those with other [[genotype]]s.<ref name="pmid21511329">{{cite journal| author=Hughes SA, Wedemeyer H, Harrison PM| title=Hepatitis delta virus. | journal=Lancet | year= 2011 | volume= 378 | issue= 9785 | pages= 73-85 | pmid=21511329 | doi=10.1016/S0140-6736(10)61931-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21511329 }} </ref> | ||
===Nucleotide and Nucleoside Analogues=== | ===Nucleotide and Nucleoside Analogues=== | ||
Revision as of 19:09, 16 August 2014
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Hepatitis D |
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Diagnosis |
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Treatment |
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Hepatitis D medical therapy On the Web |
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American Roentgen Ray Society Images of Hepatitis D medical therapy |
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Risk calculators and risk factors for Hepatitis D medical therapy |
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
Currently there is no effective antiviral therapy available for the treatment of acute or chronic hepatitis D.[1]
Medical Therapy
The goal of treatment in hepatitis D is the clearance of HDV and HBV helper virus. The complexity of the treatment resides in the need to address both viruses, and in the simplicity of HDV. The fact that HDV uses host cell's enzymes for its replication, limits the number of targets for therapeutic agents.[2]
Immunosuppressive agents do not have any effect on hepatitis D.[3][4]
Interferon-α
Interferon-α is the only drug that has shown antiviral activity against HDV. Both forms of the drug (conventional and pegylated) are able to inhibit HDV replication cycle. The effect of interferon is considered to be an indirect one, possibly via an effect on the helper hepadnavirus and/or on the immune response.[2][3][5]
For some infected patients, the following doses have yielded remission of the disease:[3][4]
- 9 million units three times a week, for 12 months
- 5 million units daily for up to 12 months
However, most patients remained positive for HDV RNA, despite the improved disease conditions.[3]
Even with some discrepancies among studies, relating to dose, form of administration, and treatment duration with interferon-α:[6][7]
- 25-40% of patients showed sustained response to treatment, 1 to 2 years after therapy.
- According to the HIDIT I trial, about 28% of the patients who were treated with 180 μg of pegylated interpheron-α/week, for 48 weeks, were cured. When combined with adefovir, treatment caused a greater decline in the HBsAg levels.
- Patients treated with higher doses of interferon-α showed better outcomes than those treated with lower doses of interferon.
- Higher doses were associated with a decrease of HBsAg, RNA, inflammatory activity, and fibrosis.
- Prolonged therapies have shown better response rates, however, it is not clear which patients should stop and which should continue the treatment after the first year.
- One study with prolonged treatment for 12 years induced clearance of HDV RNA and HBsAg, as well as regression of fibrosis.
Treatment depends on the severity of the disease:[8]
- Patients with decompensated cirrhosis should not be treated with interferon-α
- Mild disease may not require immediate antiviral treatment
Patients infected with HDV genotype 1 have worst responses to pegylated interferon than those with other genotypes.[8]
Nucleotide and Nucleoside Analogues
Studies have not demonstrated short-term antiviral effect of nucleotide and nucleoside analogues (NUCs) on HDV.
However, long-term treatment with these drugs was shown to cause a decline in the HBsAg levels in some patients. Because the suppression of HBV DNA replication is related to a decrease in the risk of developing progressive liver disease, NUC therapy is recommended for patients with HDV infection and a high HBV viral load.
Some studies concluded that prolonged therapy with tenofovir of patients coinfected with HDV-HBV-HIV, lead to a significant decline in HBsAg, HDV DNA, with some patients becoming HDV RNA negative.[9][10] NUC therapy is recommended in HIV patients with high viral load.[11][8][12]
Chronic Hepatitis
Patients with chronic hepatitis should be treated with weekly injections of pegylated interferon, initially for 48 weeks. Patients who should be considered for this treatment regimen include those with:[8]
- HDV RNA active replication
- Active disease, evidenced by histologic abnormalities
- No contraindications to pegylated interferon
Patients who fail to achieve HDV RNA clearance after 48 weeks should have individualized therapy.
Patients who may benefit from extension of the treatment to 72 weeks include those with:[8]
- Resolving transaminitis
- Decreasing viral load
- Progressive decrease of HBsAg titre
- Decreasing IgM antibody titer
If the patient's condition is improving and side-effects are tolerated, treatment duration may be prolonged beyond the 72 weeks. In patients with elevated levels of HBV DNA, a NUC should be added to the treatment in order to inhibit HBV replication. For those in which HDV has been controlled, if HBV replication reoccurs, potent NUCs are the treatment of choice. These drugs may also be used in patients with low levels of serum HBV DNA, with liver disease, who are therefore not eligible for treatment with pegylated interferon.[8]
References
- ↑ Fields, Bernard (2013). Fields virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 9781451105636.
- ↑ 2.0 2.1 Heidrich, Benjamin; Manns, Michael P.; Wedemeyer, Heiner (2012). "Treatment Options for Hepatitis Delta Virus Infection". Current Infectious Disease Reports. 15 (1): 31–38. doi:10.1007/s11908-012-0307-z. ISSN 1523-3847.
- ↑ 3.0 3.1 3.2 3.3 "Hepatitis D Prevention and treatment".
- ↑ 4.0 4.1 Lau DT, Kleiner DE, Park Y, Di Bisceglie AM, Hoofnagle JH (1999). "Resolution of chronic delta hepatitis after 12 years of interferon alfa therapy". Gastroenterology. 117 (5): 1229–33. PMID 10535887.
- ↑ Farci, Patrizia; Mandas, Antonella; Coiana, Alessandra; Lai, Maria Eliana; Desmet, Valeer; Van Eyken, Peter; Gibo, Yukio; aruso, Luciano; Scaccabarozzi, Sergio; Criscuolo, Domenico; Ryff, Jean-Charles; Balestrieri, Angelo (1994). "Treatment of Chronic Hepatitis D with Interferon Alfa-2a". New England Journal of Medicine. 330 (2): 88–94. doi:10.1056/NEJM199401133300202. ISSN 0028-4793.
- ↑ Farci, Patrizia; Roskams, Tania; Chessa, Luchino; Peddis, Giovanna; Mazzoleni, Anna Paola; Scioscia, Rosetta; Serra, Giancarlo; Lai, Maria Eliana; Loy, Maurizio; Caruso, Luciano (2004). "Long-term benefit of interferon α therapy of chronic hepatitis D: regression of advanced hepatic fibrosis". Gastroenterology. 126 (7): 1740–1749. doi:10.1053/j.gastro.2004.03.017. ISSN 0016-5085.
- ↑ Farci P, Roskams T, Chessa L, Peddis G, Mazzoleni AP, Scioscia R; et al. (2004). "Long-term benefit of interferon alpha therapy of chronic hepatitis D: regression of advanced hepatic fibrosis". Gastroenterology. 126 (7): 1740–9. PMID 15188169.
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 Hughes SA, Wedemeyer H, Harrison PM (2011). "Hepatitis delta virus". Lancet. 378 (9785): 73–85. doi:10.1016/S0140-6736(10)61931-9. PMID 21511329.
- ↑ Sheldon J, Ramos B, Toro C, Ríos P, Martínez-Alarcón J, Bottecchia M; et al. (2008). "Does treatment of hepatitis B virus (HBV) infection reduce hepatitis delta virus (HDV) replication in HIV-HBV-HDV-coinfected patients?". Antivir Ther. 13 (1): 97–102. PMID 18389903.
- ↑ Martín-Carbonero L, Teixeira T, Poveda E, Plaza Z, Vispo E, González-Lahoz J; et al. (2011). "Clinical and virological outcomes in HIV-infected patients with chronic hepatitis B on long-term nucleos(t)ide analogues". AIDS. 25 (1): 73–9. doi:10.1097/QAD.0b013e328340fde2. PMID 21076274.
- ↑ Wedemeyer H (2010). "Re-emerging interest in hepatitis delta: new insights into the dynamic interplay between HBV and HDV". J Hepatol. 52 (5): 627–9. doi:10.1016/j.jhep.2010.02.001. PMID 20334947.
- ↑ Calle Serrano B, Manns MP, Wedemeyer H (2012). "Hepatitis delta and HIV infection". Semin Liver Dis. 32 (2): 120–9. doi:10.1055/s-0032-1316467. PMID 22760651.