Hepatitis D medical therapy

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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 acute or chronic hepatitis D.[1] Interferon-α is the only drug that has demonstrated antiviral activity, albeit modest, against HDV. Patients with chronic hepatitis should be treated with weekly injections of pegylated interferon for at least 48 weeks.[2][3]

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.[4]

Immunosuppressive agents have not shown any effect on hepatitis D.[3][5]

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.[4][3][6]

For some infected patients, the following doses have yielded remission of the disease:[3][5]

  • 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:[7][8]

  • 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:[2]

Patients infected with HDV genotype 1 have worst responses to pegylated interferon than those with other genotypes.[2]

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][2][12]

Chronic Hepatitis

Patients with chronic hepatitis should be treated with weekly injections of pegylated interferon, for at least 48 weeks. Patients who should be considered for this treatment regimen include those with:[2]

Patients who fail to achieve HDV RNA clearance after 48 weeks should have individualized therapy.[2]

Patients who may benefit from the extension of the treatment to 72 weeks include those with:[2]

  • 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.[2] 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.[2]

Related Chapters

References

  1. Fields, Bernard (2013). Fields virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 9781451105636.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 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.
  3. 3.0 3.1 3.2 3.3 3.4 "Hepatitis D Prevention and treatment".
  4. 4.0 4.1 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.
  5. 5.0 5.1 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.

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