Induction of oral immune regulation towards liver-extracted proteins for treatment of chronic HBV and HCV hepatitis: results of a phase I clinical trial

  1. Eran Israeli1,
  2. Rifaat Safadi1,
  3. Alaa Melhem1,
  4. Orit Pappo2,
  5. Oren Shibolet1,
  6. Athalia Klein1,
  7. Nilla Hemed1,
  8. Barbara Thalenfeld3,
  9. Dean Engelhardt3,
  10. Elazar Rabbani3,
  11. Yaron Ilan1

Article first published online: 5 JUL 2004

DOI: 10.1111/j.1478-3231.2004.0935.x

Issue

Liver International

Liver International

Volume 24, Issue 4, pages 295–307, August 2004

Additional Information

How to Cite

Israeli, E., Safadi, R., Melhem, A., Pappo, O., Shibolet, O., Klein, A., Hemed, N., Thalenfeld, B., Engelhardt, D., Rabbani, E. and Ilan, Y. (2004), Induction of oral immune regulation towards liver-extracted proteins for treatment of chronic HBV and HCV hepatitis: results of a phase I clinical trial. Liver International, 24: 295–307. doi: 10.1111/j.1478-3231.2004.0935.x

Author Information

  1. 1

    Liver Unit, Department of Medicine

  2. 2

    Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

  3. 3

    ENZO. Biochem, New York, USA

*Yaron Ilan, MD, Liver Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, PO Box 12000, Jerusalem IL-91120, Israel. Tel: +972-2-6777816 Fax: +972-2-6431021 e-mail: ilan@hadassah.org.il

Publication History

  1. Issue published online: 5 JUL 2004
  2. Article first published online: 5 JUL 2004
  3. Received 15 January 2004, accepted 1 March 2004

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (183K)

Keywords:

  • hepatitis B virus;
  • hepatitis C virus;
  • oral tolerance

Abstract: Background: Anti-viral immunity can be modulated via oral feeding of viral proteins. Hepatitis B and C viral (HBV, HCV)-associated hepatocellular injury is mediated by a defective host anti-viral immune response.

Aims: To determine the effect of oral administration of a mixture of liver-extracted proteins with HBV/HCV proteins, on viral load, liver injury, and the anti-viral T-cell response of chronic HBV/HCV patients.

Methods: Fourteen patients with chronic HBV and 15 patients with chronic HCV were treated orally with hepatocyte-extracted proteins and HBV or HCV viral proteins for 24 weeks, and followed for an additional 26 weeks. Patients were monitored for HBV-DNA or HCV-RNA levels, liver enzymes and liver histology. Viral-directed T-cell immunity was assessed by IFNγ and IL10 ELISPOT, viral-specific T-cell proliferation, cytotoxicity, and cytokines assays, and followed for peripheral natural killer T-cell (NKT) number.

Results: In both chronic HBV and HCV patients, oral administration of a mixture of selected liver-extracted proteins and viral proteins induced a favorable increase in viral-specific T-cell proliferation, and IFNγ-secreting clones, along with a significant decrease in the anti-viral IL10-secreting T-cell clones. However, the effects of modulation of the anti-viral immunity differed between the HBV and HCV patients. In both groups, no major adverse events were noted. In chronic HBV patients, a significant decrease in viral load was observed in 5/14 (35.7%) of patients. HB surface antigen/HB nucleocapsid antigen scores on liver biopsy improved in 46.1% and 50%, respectively, and the histological necroinflammatory score improved in 4/13 (30.7%). Forty percent of the patients with elevated liver enzymes showed a favorable biochemical response. In contrast, an improvement in the histological necroinflammatory score was observed in only 2/12 (17%) of the chronic HCV patients. No significant decrease in HCV RNA was noted in any of these patients.

Conclusions: Immune regulation of the anti-HBV/HCV immune response via oral administration of a mixture of liver-extracted and viral proteins significantly altered the viral-specific immunity. This effect was associated with clinical and virological improvements in chronic HBV patients.

View Full Article (HTML) Get PDF (183K)