Blood Purif 2010;29:210–215

Modeling Hepatitis C Virus Therapies Combining Drugs and Lectin Affinity Plasmapheresis

Tullis R.H.a · Duffin R.P.a · Ichim T.E.b · Joyce J.A.a · Levin N.W.c
aAethlon Medical Inc. and bMedistem Inc., San Diego, Calif., and cRenal Research Institute, New York, N.Y., USA
email Corresponding Author

 goto top of outline Key Words

  • Hepatitis C virus
  • Lectin affinity
  • Hemodialysis
  • Plasmapheresis
  • Mathematical models
  • Galanthus nivalis agglutinin

 goto top of outline Abstract

Hepatitis C virus (HCV) infection can be cured by standard pegylated interferon (IFN) + ribavirin drug therapy in 30–50% of treatment-naïve genotype 1 HCV patients. Cure rate is defined as a sustained viral response measured 6 months after the end of treatment. Recently, Fujiwara et al. [Hepatol Res 2007;37:701–710], using a double-filtration plasmapheresis (DFPP) technique, showed that simple physical reduction in circulating HCV using a 1-week pretreatment increased the cure rate for treatment-naïve type 1 HCV patients from 50 (controls) to 78% (treated). For previous nonresponders, the cure rate increased from 30 to 71%. This effect occurs even though the DFPP per treatment HCV viral load reduction averaged 26%. In clinical studies discussed here, a lectin affinity plasmapheresis (LAP) device caused an estimated 41% decrease in viral load as previously reported. A more detailed analysis using normalized data to correct for any variations in initial viral load gave an average 29% per treatment viral load reduction in 5 HCV-positive dialysis patients. The latter data indicate that continuous application of LAP could bring HCV viral load to undetectable levels in 4.1 days. Compared to DFPP, the LAP approach has the advantage that no plasma losses are incurred. In addition hemopurification can be carried out for extended periods of time analogous to continuous renal replacement therapy for the treatment of acute kidney failure, making the process much more effective. Calculations based on these data predict that continuous hemopurification would substantially increase the rate of viral load reduction (approx. 14-fold) and therefore increase the cure rate for HCV standard-of-care drug therapies without adding additional drugs and their associated side effects.

Copyright © 2010 S. Karger AG, Basel

 goto top of outline References
  1. Kim WR: The burden of hepatitis C in the United States. Hepatology 2002;36(suppl 1):S30–S34.

    External Resources

  2. National Institutes of Health Consensus Development Conference Statement: Management of hepatitis C 2002 (June 10–12, 2002). Gastroenterology 2002;123:2082–2099.
  3. Rosen HR, Ribeiro RR, Weinberger L, Wolf S, Chung M, Gretch DR, Perelson AS: Early hepatitis C viral kinetics correlate with long-term outcome in patients receiving high dose induction followed by combination interferon and ribavirin therapy. J Hepatol 2002;37:124–130.
  4. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB: Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009.
  5. Tullis R, Scammura D, Ambrus J: Affinity hemodialysis for antiviral therapy with specific application to HIV. J Theor Med 2002;3:157–166.

    External Resources

  6. Tullis RH: Method for removal of viruses from blood using lectin affinity hemodialysis. San Diego, Aethlon Medical Inc, 2007.
  7. Tullis RH, Duffin RP, Handley HH, Sodhi P, Menon J, Joyce JA, Kher V: Reduction of hepatitis C virus using lectin affinity plasmapheresis in dialysis patients. Blood Purif 2009;27:64–69.
  8. Tullis RH, Duffin RP, Zech M, Ambrus JL Jr: Affinity hemodialysis for antiviral therapy. I. Removal of HIV-1 from cell culture supernatants, plasma, and blood. Ther Apher 2002;6:213–220.
  9. Badalamenti S, Catania A, Lunghi G, Covini G, Bredi E, Brancaccio D, Salvadori M, Como G, Ponticelli C, Graziani G: Changes in viremia and circulating interferon-alpha during hemodialysis in hepatitis C virus-positive patients: only coincidental phenomena? Am J Kidney Dis 2003;42:143–150.
  10. Mizuno M, Higuchi T, Yanai M, Kanmatsuse K, Esumi M: Dialysis-membrane-dependent reduction and adsorption of circulating hepatitis C virus during hemodialysis. Nephron 2002;91:235–242.
  11. Fabrizi F, Bunnapradist S, Lunghi G, Martin P: Kinetics of hepatitis C virus load during hemodialysis: novel perspectives. J Nephrol 2003;16:467–475.
  12. Takada Y, Ito T, Ueda Y, Haga H, Egawa H, Tanaka K, Uemoto S: Effects of double-filtration plasmapheresis combined with interferon plus ribavirin for recurrent hepatitis C after living donor liver transplantation. Liver Transpl 2008;14:1044–1047.
  13. Fujiwara K, Kaneko S, Kakumu S, Sata M, Hige S, Tomita E, Mochida S: Double filtration plasmapheresis and interferon combination therapy for chronic hepatitis C patients with genotype 1 and high viral load. Hepatol Res 2007;37:701–710.
  14. Wang WK, Chao DY, Kao CL, Wu HC, Liu YC, Li CM, Lin SC, Ho ST, Huang JH, King CC: High levels of plasma dengue viral load during defervescence in patients with dengue hemorrhagic fever: implications for pathogenesis. Virology 2003;305:330–338.
  15. Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, Endy TP, Raengsakulrach B, Rothman AL, Ennis FA, Nisalak A: Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis 2000;181:2–9.
  16. Drosten C, Gottig S, Schilling S, Asper M, Panning M, Schmitz H, Gunther S: Rapid detection and quantification of RNA of Ebola and Marburg viruses, Lassa virus, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, dengue virus, and yellow fever virus by real-time reverse transcription-PCR. J Clin Microbiol 2002;40:2323–2330.
  17. Towner JS, Rollin PE, Bausch DG, Sanchez A, Crary SM, Vincent M, Lee WF, Spiropoulou CF, Ksiazek TG, Lukwiya M, Kaducu F, Downing R, Nichol ST: Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome. J Virol 2004;78:4330–4341.
  18. Rivera M, Gentil MA, Sayago M, Gonzalez Roncero F, Trigo C, Algarra G, Pereira P, Valdivia MA, Aguilar J: Treatment of hepatitis C virus with interferon in hemodialysis patients awaiting kidney transplant. Transplant Proc 2005;37:1424–1425.
  19. Kao JH, Lai MY, Chen PJ, Hwang LH, Chen DS: Serum hepatitis C virus titers in the progression of type C chronic liver disease. With special emphasis on patients with type 1b infection. J Clin Gastroenterol 1996;23:280–283.
  20. Shiffman ML, Hofmann CM, Thompson EB, Ferreira-Gonzalez A, Contos MJ, Koshy A, Luketic VA, Sanyal AJ, Mills AS, Garrett CT: Relationship between biochemical, virological, and histological response during interferon treatment of chronic hepatitis C. Hepatology 1997;26:780–785.
  21. Bossi P: Genital herpes: epidemiology, transmission, clinic, asymptomatic viral excretion, impact on other sexually transmitted diseases, prevention, and treatment. Ann Dermatol Venereol 2002;129:477–493.
  22. Haas J, Meyding-Lamade U, Fath A, Stingele K, Storch-Hagenlocher B, Wildemann B: Acyclovir treatment of experimentally induced herpes simplex virus encephalitis: monitoring the changes in immunologic NO synthase expression and viral load within brain tissue of SJL mice. Neurosci Lett 1999;264:129–132.
  23. Clerici M: Immunomodulants for the treatment of HIV infection: the search goes on. Expert Opin Investig Drugs 2006;15:197–200.
  24. Rathbun RC, Lockhart SM, Stephens JR: Current HIV treatment guidelines – an overview. Curr Pharm Des 2006;12:1045–1063.
  25. Levy JA: HIV pathogenesis and long-term survival. Aids 1993;7:1401–1410.
  26. Buchbinder SP, Katz MH, Hessol NA, O’Malley PM, Holmberg SD: Long-term HIV-1 infection without immunologic progression. Aids 1994;8:1123–1128.
  27. Deacon NJ, Tsykin A, Solomon A, Smith K, Ludford-Menting M, Hooker DJ, McPhee DA, Greenway AL, Ellett A, Chatfield C, Lawson VA, Crowe S, Maerz A, Sonza S, Learmont J, Sullivan JS, Cunningham A, Dwyer D, Dowton D, Mills J: Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 1995;270:988–991.
  28. Cohen J: Controls sought. Science 2006;313:1029.
  29. Oxford JS, Mann A, Lambkin R: A designer drug against influenza: the NA inhibitor oseltamivir (Tamiflu). Expert Rev Anti Infect Ther 2003;1:337–342.
  30. McClellan K, Perry CM: Oseltamivir: a review of its use in influenza. Drugs 2001;61:263–283.
  31. Nikiforov V, Turovskii I, Kalinin P, Akinfeeva L, Katkova L, Barmin V, Riabchikova E, Popkova N, Shestopalov A, Nazarov V, et al: A case of a laboratory infection with Marburg fever. Zh Mikrobiol Epidemiol Immunobiol 1994;3:104–106.

    External Resources

  32. Terajima M, Hendershot JD 3rd, Kariwa H, Koster FT, Hjelle B, Goade D, DeFronzo MC, Ennis FA: High levels of viremia in patients with the Hantavirus pulmonary syndrome. J Infect Dis 1999;180:2030–2034.
  33. Veillon P, Payan C, Picchio G, Maniez-Montreuil M, Guntz P, Lunel F: Comparative evaluation of the total hepatitis C virus core antigen, branched-DNA, and Amplicor monitor assays in determining viremia for patients with chronic hepatitis C during interferon plus ribavirin combination therapy. J Clin Microbiol 2003;41:3212–3220.

 goto top of outline Author Contacts

Richard H. Tullis, PhD
Aethlon Medical Inc., 3030 Bunker Hill Street
San Diego, CA 92109 (USA)
Tel. +1 858 459 7800, ext. 304, Fax +1 858 272 2738

 goto top of outline Article Information

Published online: January 8, 2010
Number of Print Pages : 6
Number of Figures : 2, Number of Tables : 2, Number of References : 33

 goto top of outline Publication Details

Blood Purification

Vol. 29, No. 2, Year 2010 (Cover Date: January 2010)

Journal Editor: Ronco C. (Vicenza)
ISSN: 0253-5068 (Print), eISSN: 1421-9735 (Online)

For additional information:

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