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. 1985 Jul;26(7):745–751. doi: 10.1136/gut.26.7.745

Randomised controlled trial of adenine arabinoside 5'-monophosphate (ARA-AMP) in chronic hepatitis B virus infection.

I V Weller, A S Lok, A Mindel, P Karayiannis, S Galpin, J Monjardino, S Sherlock, H C Thomas
PMCID: PMC1433015  PMID: 2410328

Abstract

A randomised controlled trial was conducted in 29 HBV carriers who had been HBs and HBe antigen positive for more than six months. Fifteen patients were treated with ARA-AMP 10 mg/kg/day given as intramuscular injections 12 hours apart for five days followed by 5 mg/kg/day for 23 days. The 14 controls received no treatment. Serum HBV-DNA polymerase, and HBV-DNA decreased in all patients during therapy. Six treated patients lost serum HBV-DNA polymerase, HBV-DNA and HBeAg, HBsAg concentrations decreased, and five developed anti-HBe. One of these six patients lost HBsAg and developed anti-HBs. No such changes were observed in the control group over a similar 18 month period of observation. A four week course of ARA-AMP inhibits HBV replication and in a significant minority of patients this is long lasting and is associated with a reduced level of inflammatory activity in the liver.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bassendine M. F., Chadwick R. G., Salmeron J., Shipton U., Thomas H. C., Sherlock S. Adenine arabinoside therapy in HBsAg-positive chronic liver disease: a controlled study. Gastroenterology. 1981 May;80(5 Pt 1):1016–1022. [PubMed] [Google Scholar]
  2. Berninger M., Hammer M., Hoyer B., Gerin J. L. An assay for the detection of the DNA genome of hepatitis B virus in serum. J Med Virol. 1982;9(1):57–68. doi: 10.1002/jmv.1890090109. [DOI] [PubMed] [Google Scholar]
  3. Chadwick R. G., Bassendine M. F., Crawford E. M., Thomas H. C., Sherlock S. HBsAg-positive chronic liver disease: inhibition of DNA polymerase activity by vidarabine. Br Med J. 1978 Aug 19;2(6136):531–533. doi: 10.1136/bmj.2.6136.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Craxi A., Weller I. V., Bassendine M. F., Fowler M. J., Monjardino J., Thomas H. C., Sherlock S. Relationship between HBV-specific DNA polymerase and HBe antigen/antibody system in chronic HBV infection: factors determining selection of patients and outcome of antiviral therapy. Gut. 1983 Feb;24(2):143–147. doi: 10.1136/gut.24.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Frommel D., Allain J. P., Courouce A. M., Derose S., Trepo D., Crivelli O., Rizzetto M. Long-lasting abatement of HBsAg synthesis induced by acute delta infection. Lancet. 1983 Mar 19;1(8325):656–657. doi: 10.1016/s0140-6736(83)91835-4. [DOI] [PubMed] [Google Scholar]
  6. Goodall A. H., Meek F. L., Waters J. A., Miescher G. C., Janossy G., Thomas H. C. A rapid one-step radiometric assay for hepatitis B surface antigen utilizing monoclonal antibodies. J Immunol Methods. 1982 Jul 30;52(2):167–174. doi: 10.1016/0022-1759(82)90042-4. [DOI] [PubMed] [Google Scholar]
  7. Hoofnagle J. H., Dusheiko G. M., Seeff L. B., Jones E. A., Waggoner J. G., Bales Z. B. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Ann Intern Med. 1981 Jun;94(6):744–748. doi: 10.7326/0003-4819-94-6-744. [DOI] [PubMed] [Google Scholar]
  8. Hoofnagle J. H., Minuk G. Y., Dusheiko G. M., Schafer D. F., Johnson R., Straus S., Jones E. A., Gerin J. L., Ishak K. Adenine arabinoside 5'-monophosphate treatment of chronic type B hepatitis. Hepatology. 1982 Nov-Dec;2(6):784–788. doi: 10.1002/hep.1840020606. [DOI] [PubMed] [Google Scholar]
  9. Marion P. L., Oshiro L. S., Regnery D. C., Scullard G. H., Robinson W. S. A virus in Beechey ground squirrels that is related to hepatitis B virus of humans. Proc Natl Acad Sci U S A. 1980 May;77(5):2941–2945. doi: 10.1073/pnas.77.5.2941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Novick D. M., Lok A. S., Thomas H. C. Diminished responsiveness of homosexual men to antiviral therapy for HBsAg-positive chronic liver disease. J Hepatol. 1985;1(1):29–35. doi: 10.1016/s0168-8278(85)80065-9. [DOI] [PubMed] [Google Scholar]
  11. Peto R., Pike M. C., Armitage P., Breslow N. E., Cox D. R., Howard S. V., Mantel N., McPherson K., Peto J., Smith P. G. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer. 1976 Dec;34(6):585–612. doi: 10.1038/bjc.1976.220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pollard R. B., Smith J. L., Neal A., Gregory P. B., Merigan T. C., Robinson W. S. Effect of vidarabine on chronic hepatitis B virus infection. JAMA. 1978 Apr 21;239(16):1648–1650. [PubMed] [Google Scholar]
  13. Realdi G., Alberti A., Rugge M., Bortolotti F., Rigoli A. M., Tremolada F., Ruol A. Seroconversion from hepatitis B e antigen to anti-HBe in chronic hepatitis B virus infection. Gastroenterology. 1980 Aug;79(2):195–199. [PubMed] [Google Scholar]
  14. Rizzetto M., Canese M. G., Gerin J. L., London W. T., Sly D. L., Purcell R. H. Transmission of the hepatitis B virus-associated delta antigen to chimpanzees. J Infect Dis. 1980 May;141(5):590–602. doi: 10.1093/infdis/141.5.590. [DOI] [PubMed] [Google Scholar]
  15. Rizzetto M., Shih J. W., Gerin J. L. The hepatitis B virus-associated delta antigen: isolation from liver, development of solid-phase radioimmunoassays for delta antigen and anti-delta and partial characterization of delta antigen. J Immunol. 1980 Jul;125(1):318–324. [PubMed] [Google Scholar]
  16. Rizzetto M., Verme G., Recchia S., Bonino F., Farci P., Aricò S., Calzia R., Picciotto A., Colombo M., Popper H. Chronic hepatitis in carriers of hepatitis B surface antigen, with intrahepatic expression of the delta antigen. An active and progressive disease unresponsive to immunosuppressive treatment. Ann Intern Med. 1983 Apr;98(4):437–441. doi: 10.7326/0003-4819-98-4-437. [DOI] [PubMed] [Google Scholar]
  17. Scullard G. H., Andres L. L., Greenberg H. B., Smith J. L., Sawhney V. K., Neal E. A., Mahal A. S., Popper H., Merigan T. C., Robinson W. S. Antiviral treatment of chronic hepatitis B virus infection: improvement in liver disease with interferon and adenine arabinoside. Hepatology. 1981 May-Jun;1(3):228–232. doi: 10.1002/hep.1840010306. [DOI] [PubMed] [Google Scholar]
  18. Scullard G. H., Pollard R. B., Smith J. L., Sacks S. L., Gregory P. B., Robinson W. S., Merigan T. C. Antiviral treatment of chronic hepatitis B virus infection. I. Changes in viral markers with interferon combined with adenine arabinoside. J Infect Dis. 1981 Jun;143(6):772–783. doi: 10.1093/infdis/143.6.772. [DOI] [PubMed] [Google Scholar]
  19. Scullard G. H., Smith C. I., Merigan T. C., Robinson W. S., Gregory P. B. Effects of immunosuppressive therapy on viral markers in chronic active hepatitis B. Gastroenterology. 1981 Dec;81(6):987–991. [PubMed] [Google Scholar]
  20. Viola L. A., Barrison I. G., Coleman J. C., Murray-Lyon I. M. The clinical course of acute type A hepatitis in chronic HBsAg carriers--a report of 3 cases. Postgrad Med J. 1982 Feb;58(676):80–81. doi: 10.1136/pgmj.58.676.80. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Viola L. A., Barrison I. G., Coleman J. C., Paradinas F. J., Fluker J. L., Evans B. A., Murray-Lyon I. M. Natural history of liver disease in chronic hepatitis B surface antigen carriers. Survey of 100 patients from Great Britain. Lancet. 1981 Nov 21;2(8256):1156–1159. doi: 10.1016/s0140-6736(81)90600-0. [DOI] [PubMed] [Google Scholar]
  22. Weller I. V., Bassendine M. F., Craxi A., Fowler M. J., Monjardino J., Thomas H. C., Sherlock S. Successful treatment of HBs and HBeAg positive chronic liver disease: prolonged inhibition of viral replication by highly soluble adenine arabinoside 5'-monophosphate (ARA-AMP). Gut. 1982 Sep;23(9):717–723. doi: 10.1136/gut.23.9.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Weller I. V., Bassendine M. F., Murray A. K., Craxi A., Thomas H. C., Sherlock S. Effects of prednisolone/azathioprine in chronic hepatitis B viral infection. Gut. 1982 Aug;23(8):650–655. doi: 10.1136/gut.23.8.650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Weller I. V., Fowler M. J., Monjardino J., Thomas H. C. The detection of HBV-DNA in serum by molecular hybridisation: a more sensitive method for the detection of complete HBV particles. J Med Virol. 1982;9(4):273–280. doi: 10.1002/jmv.1890090405. [DOI] [PubMed] [Google Scholar]
  25. Weller I. V., Karayiannis P., Lok A. S., Montano L., Bamber M., Thomas H. C., Sherlock S. Significance of delta agent infection in chronic hepatitis B virus infection: a study in British carriers. Gut. 1983 Nov;24(11):1061–1063. doi: 10.1136/gut.24.11.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]

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