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

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.